首页 > 最新文献

BMC Pharmacology & Toxicology最新文献

英文 中文
Determination of biochemical and histopathological changes on testicular and epididymis tissues induced by exposure to insecticide Imidacloprid during postnatal development in rats. 杀虫剂吡虫啉对大鼠出生后发育过程中睾丸和附睾组织生化及病理变化的影响。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-27 DOI: 10.1186/s40360-023-00709-3
Amina Sardar, Mehwish David, Sarwat Jahan, Tayyaba Afsar, Aneela Ahmad, Asad Ullah, Ali Almajwal, Huma Shafique, Suhail Razak

Background: Imidacloprid is a neonicotinoid insecticide belonging to the chloronicotinyl nitroguanidine chemical family. Toxicity of IMD for mammals in scientific studies has shown high mutagenic, immunotoxic, teratogenic and neurotoxic effects. The present study was designed to assess the toxic effects of imidacloprid (IMD) on the testicular and epididymis tissues as well as testosterone levels of neonatal male rats.

Methods: Neonatal male rats from postnatal day (PND) 1 to PND 26 were consecutively administered with different concentrations of IMD (1, 5 and 10 mg/kg) subcutaneously. The effect of IMD on body and organ weight, lipid profile, histopathological alterations, oxidative stress and altered testosterone levels were assessed in the testis and plasma.

Results: The results of body weight gain showed a significant difference in group 4 (10 mg/kg) animals as compared to the control. A significant increase in total cholesterol and triglycerides, while a decrease in high-density lipoprotein concentrations was evident. Similarly, a significant decrease in concentrations of antioxidant enzymes (CAT and SOD) among all the IMD-treated groups was evident, when compared to the control. Increased production of ROS was also noticed in the highest-dose treatment group. Further, we observed that IMD-treated rats indicated histopathological changes in the testis and epididymis along with a significant decrease in the plasma testosterone concentrations among IMI-treated groups in contrast to the control. Histological examination of the testis of IMD-treated neonatal male rats also showed decreased spermatogenesis in the treated groups when compared to the control. Furthermore, an increase in lumen diameter and a decrease in epithelial height of seminiferous tubules were also observed in IMD-treated rats in comparison with the control.

Conclusion: It is concluded that sub-chronic exposure to IMD in neonatal male rats may induce histopathological changes in reproductive tissues and damage normal testicular functions via inducing oxidative stress, decrease in body weight, disturbing normal blood lipid profile and testosterone concentration. IMD exposure can induce pathophysiological effects calls for further evaluation of this widely used insecticide.

背景:吡虫啉是一种新烟碱类杀虫剂,属于氯烟碱基硝基胍化学家族。在科学研究中,IMD对哺乳动物的毒性显示出高度的诱变、免疫毒性、致畸和神经毒性作用。本研究旨在评估吡虫啉(IMD)对新生雄性大鼠睾丸和附睾组织以及睾酮水平的毒性作用。方法:从出生后第1天(PND)至第26天,雄性新生大鼠连续皮下注射不同浓度的IMD(1、5、10 mg/kg)。在睾丸和血浆中评估IMD对身体和器官重量、脂质谱、组织病理学改变、氧化应激和睾酮水平改变的影响。结果:与对照组相比,第4组(10 mg/kg)的增重结果有显著差异。总胆固醇和甘油三酯显著增加,而高密度脂蛋白浓度明显下降。同样,与对照组相比,所有imd处理组的抗氧化酶(CAT和SOD)浓度明显降低。在最高剂量治疗组中,ROS的产生也有所增加。此外,我们观察到,与对照组相比,imd治疗组大鼠的睾丸和附睾出现了组织病理学变化,血浆睾酮浓度显著降低。imd治疗的新生雄性大鼠睾丸的组织学检查也显示,与对照组相比,治疗组的精子发生减少。此外,与对照组相比,imd治疗大鼠的管腔直径增加,精小管上皮高度降低。结论:亚慢性暴露IMD可引起新生雄性大鼠生殖组织病理改变,并通过诱导氧化应激、体重下降、扰乱正常血脂和睾酮浓度等途径损害正常睾丸功能。暴露于IMD可引起病理生理效应,需要进一步评估这种广泛使用的杀虫剂。
{"title":"Determination of biochemical and histopathological changes on testicular and epididymis tissues induced by exposure to insecticide Imidacloprid during postnatal development in rats.","authors":"Amina Sardar, Mehwish David, Sarwat Jahan, Tayyaba Afsar, Aneela Ahmad, Asad Ullah, Ali Almajwal, Huma Shafique, Suhail Razak","doi":"10.1186/s40360-023-00709-3","DOIUrl":"10.1186/s40360-023-00709-3","url":null,"abstract":"<p><strong>Background: </strong>Imidacloprid is a neonicotinoid insecticide belonging to the chloronicotinyl nitroguanidine chemical family. Toxicity of IMD for mammals in scientific studies has shown high mutagenic, immunotoxic, teratogenic and neurotoxic effects. The present study was designed to assess the toxic effects of imidacloprid (IMD) on the testicular and epididymis tissues as well as testosterone levels of neonatal male rats.</p><p><strong>Methods: </strong>Neonatal male rats from postnatal day (PND) 1 to PND 26 were consecutively administered with different concentrations of IMD (1, 5 and 10 mg/kg) subcutaneously. The effect of IMD on body and organ weight, lipid profile, histopathological alterations, oxidative stress and altered testosterone levels were assessed in the testis and plasma.</p><p><strong>Results: </strong>The results of body weight gain showed a significant difference in group 4 (10 mg/kg) animals as compared to the control. A significant increase in total cholesterol and triglycerides, while a decrease in high-density lipoprotein concentrations was evident. Similarly, a significant decrease in concentrations of antioxidant enzymes (CAT and SOD) among all the IMD-treated groups was evident, when compared to the control. Increased production of ROS was also noticed in the highest-dose treatment group. Further, we observed that IMD-treated rats indicated histopathological changes in the testis and epididymis along with a significant decrease in the plasma testosterone concentrations among IMI-treated groups in contrast to the control. Histological examination of the testis of IMD-treated neonatal male rats also showed decreased spermatogenesis in the treated groups when compared to the control. Furthermore, an increase in lumen diameter and a decrease in epithelial height of seminiferous tubules were also observed in IMD-treated rats in comparison with the control.</p><p><strong>Conclusion: </strong>It is concluded that sub-chronic exposure to IMD in neonatal male rats may induce histopathological changes in reproductive tissues and damage normal testicular functions via inducing oxidative stress, decrease in body weight, disturbing normal blood lipid profile and testosterone concentration. IMD exposure can induce pathophysiological effects calls for further evaluation of this widely used insecticide.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"68"},"PeriodicalIF":2.9,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In-silico and in-vitro screening of Asiatic acid and Asiaticoside A against Cathepsin S enzyme. 抗组织蛋白酶S酶asia - acid和asiatico苷A的体外和计算机筛选。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-25 DOI: 10.1186/s40360-023-00701-x
Temitope Akinwumi Ajani, Kenechukwu Obikeze, Zandisiwe E Magwebu, Samuel Egieyeh, Chesa G Chauke

Background: Atherosclerosis is a form of cardiovascular disease that affects the endothelium of the blood vessel. Series of events are involved in the pathophysiology of this disease which includes the breaking down of the connective tissue elastin and collagen responsible for the tensile strength of the arterial wall by proteolytic enzyme. One of these enzymes called Cathepsin S (CatS) is upregulated in the progression of the disease and its inhibition has been proposed to be a promising pharmacological target to improve the prognosis of the disease condition. Asiatic acid and asiaticoside A are both pentacyclic triterpenoids isolated from Centella asiatica. Their use in treating various cardiovascular diseases has been reported.

Methods: In this study through in silico and in vitro methods, the pharmacokinetic properties, residue interaction, and inhibitory activities of these compounds were checked against the CatS enzyme. The SwissADME online package and the ToxTree 3.01 version of the offline software were used to determine the physicochemical properties of the compounds.

Result: Asiatic acid reported no violation of the Lipinski rule while asiaticoside A violated the rule with regards to its molecular structure and size. The molecular docking was done using Molecular Operating Environment (MOE) and the S-score of - 7.25988, - 7.08466, and - 4.147913 Kcal/mol were recorded for LY300328, asiaticoside A, and asiatic acid respectively. Asiaticoside A has a docking score value (- 7.08466Kcal/mol) close to the co-crystallize compound. Apart from the close docking score, the amino acid residue glycine69 and asparagine163 both interact with the co-crystallized compound and asiaticoside A. The in vitro result clearly shows the inhibitory effect of asiaticoside and asiatic acid. Asiaticoside A has an inhibitory value of about 40% and asiatic acid has an inhibitory value of about 20%.

Conclusion: This clearly shows that asiaticoside will be a better drug candidate than asiatic acid in inhibiting the CatS enzyme for the purpose of improving the outcome of atherosclerosis. However, certain modifications need to be made to the structural make-up of asiaticoside A to improve its pharmacokinetics properties.

背景:动脉粥样硬化是一种影响血管内皮的心血管疾病。该疾病的病理生理学涉及一系列事件,包括蛋白质水解酶分解负责动脉壁拉伸强度的结缔组织弹性蛋白和胶原蛋白。其中一种名为组织蛋白酶S (CatS)的酶在疾病的进展中上调,其抑制被认为是改善疾病预后的有希望的药理学靶点。积雪草酸(Asiatic acid)和积雪草苷A (asiaticoside A)都是从积雪草中分离得到的五环三萜。它们用于治疗各种心血管疾病已有报道。方法:采用体外和体内两种方法,对这些化合物的药动学性质、残基相互作用及对cat酶的抑制活性进行了检测。使用SwissADME在线软件包和ToxTree 3.01版离线软件确定化合物的物理化学性质。结果:亚细亚酸不符合利平斯基规则,而积雪草苷A在分子结构和大小上均不符合利平斯基规则。利用分子操作环境(MOE)进行分子对接,LY300328、asiaticoside A和asiatic acid的S-score分别为- 7.25988、- 7.08466和- 4.147913 Kcal/mol。积雪草苷A的对接分数值(- 7.08466Kcal/mol)接近共结晶化合物。除对接分数相近外,氨基酸残基甘氨酸69和天冬酰胺163均与共结晶化合物和积雪草苷a相互作用,体外实验结果清楚地显示积雪草苷和积雪草酸的抑制作用。积雪草苷A的抑制值约为40%,积雪草酸的抑制值约为20%。结论:与积雪草酸相比,积雪草苷将是一个更好的抑制cat酶以改善动脉粥样硬化结局的候选药物。然而,需要对积雪草苷A的结构组成进行一定的修饰,以改善其药代动力学性质。
{"title":"In-silico and in-vitro screening of Asiatic acid and Asiaticoside A against Cathepsin S enzyme.","authors":"Temitope Akinwumi Ajani, Kenechukwu Obikeze, Zandisiwe E Magwebu, Samuel Egieyeh, Chesa G Chauke","doi":"10.1186/s40360-023-00701-x","DOIUrl":"10.1186/s40360-023-00701-x","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a form of cardiovascular disease that affects the endothelium of the blood vessel. Series of events are involved in the pathophysiology of this disease which includes the breaking down of the connective tissue elastin and collagen responsible for the tensile strength of the arterial wall by proteolytic enzyme. One of these enzymes called Cathepsin S (CatS) is upregulated in the progression of the disease and its inhibition has been proposed to be a promising pharmacological target to improve the prognosis of the disease condition. Asiatic acid and asiaticoside A are both pentacyclic triterpenoids isolated from Centella asiatica. Their use in treating various cardiovascular diseases has been reported.</p><p><strong>Methods: </strong>In this study through in silico and in vitro methods, the pharmacokinetic properties, residue interaction, and inhibitory activities of these compounds were checked against the CatS enzyme. The SwissADME online package and the ToxTree 3.01 version of the offline software were used to determine the physicochemical properties of the compounds.</p><p><strong>Result: </strong>Asiatic acid reported no violation of the Lipinski rule while asiaticoside A violated the rule with regards to its molecular structure and size. The molecular docking was done using Molecular Operating Environment (MOE) and the S-score of - 7.25988, - 7.08466, and - 4.147913 Kcal/mol were recorded for LY300328, asiaticoside A, and asiatic acid respectively. Asiaticoside A has a docking score value (- 7.08466Kcal/mol) close to the co-crystallize compound. Apart from the close docking score, the amino acid residue glycine69 and asparagine163 both interact with the co-crystallized compound and asiaticoside A. The in vitro result clearly shows the inhibitory effect of asiaticoside and asiatic acid. Asiaticoside A has an inhibitory value of about 40% and asiatic acid has an inhibitory value of about 20%.</p><p><strong>Conclusion: </strong>This clearly shows that asiaticoside will be a better drug candidate than asiatic acid in inhibiting the CatS enzyme for the purpose of improving the outcome of atherosclerosis. However, certain modifications need to be made to the structural make-up of asiaticoside A to improve its pharmacokinetics properties.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"67"},"PeriodicalIF":2.9,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of single intravenous injection of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial. 单次静脉注射艾氯胺酮对分娩镇痛后产后抑郁的影响及其机制:一项随机、双盲对照试验。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-23 DOI: 10.1186/s40360-023-00705-7
Bin Ling, Yun Zhu, Zelin Yan, Hao Chen, Hua Xu, Qi Wang, Wanyou Yu, Wei Wang

Background: The study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms.

Methods: A total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05.

Results: The incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs. 15.3%, p = 0.004 and 5.2% vs. 18.6%, p = 0.006, respectively). There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 h after delivery were similar between the two groups.

Conclusions: Single intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.

Trial registration: The trial was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .

背景:本研究旨在探讨单次静脉注射艾氯胺酮对分娩镇痛后产后抑郁(PPD)发生率的影响,并探讨其可能的机制。方法:选取经硬膜外镇痛泵分娩镇痛的产妇120例,随机分为两组。试验组胎儿脱胎后静脉注射剂量为0.2 mg/kg的艾氯胺酮,对照组给予安慰剂。记录分娩后PPD发生情况及不良反应。本研究分别在分娩镇痛前、分娩后24 h、1周和6周测量应激和炎症相关指标。采用SPSS软件(25.0版)进行独立t检验、重复测量方差分析和卡方检验。p值小于0.05,认为有统计学意义。结果:埃氯胺酮组产后1周和6周PPD发生率均显著降低(分别为3.4%比15.3%,p = 0.004和5.2%比18.6%,p = 0.006)。本研究中不同时间点的应激和炎症相关指标也存在显著差异,而两组分娩后48 h的副作用相似。结论:分娩镇痛患者分娩后单次静脉注射艾氯胺酮可降低产后1周和6周的产后抑郁发生率,且副作用未增加。艾氯胺酮的抗抑郁作用可能与减轻应激反应和炎症有关。试验注册:试验于2022年5月30日在中国临床试验注册中心注册(CTRI注册号:chictr2200060387)。注册表URL: https://www.chictr.org.cn/bin/home。
{"title":"Effect of single intravenous injection of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial.","authors":"Bin Ling, Yun Zhu, Zelin Yan, Hao Chen, Hua Xu, Qi Wang, Wanyou Yu, Wei Wang","doi":"10.1186/s40360-023-00705-7","DOIUrl":"10.1186/s40360-023-00705-7","url":null,"abstract":"<p><strong>Background: </strong>The study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms.</p><p><strong>Methods: </strong>A total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05.</p><p><strong>Results: </strong>The incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs. 15.3%, p = 0.004 and 5.2% vs. 18.6%, p = 0.006, respectively). There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 h after delivery were similar between the two groups.</p><p><strong>Conclusions: </strong>Single intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.</p><p><strong>Trial registration: </strong>The trial was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"66"},"PeriodicalIF":2.9,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials. 阿卡波糖对成人血脂的影响:随机临床试验的系统回顾和荟萃分析。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-22 DOI: 10.1186/s40360-023-00706-6
Mohsen Yousefi, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Samira Rastgoo, Reza Bagher, Alireza Khadem, Farideh Shiraseb, Omid Asbaghi

Purpose: Dyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density lipoprotein (HDL), is a major risk factor for cardiovascular diseases (CVD). Several studies have shown the potential of acarbose in improving serum lipid markers. However, there have been conflicting results on the topic in adults. Therefore, a comprehensive systematic review and meta-analysis was conducted to assess the impact of acarbose on lipid profiles.

Methods: The random-effects approach was used to combine the data, and the results were provided as weighted mean difference (WMD) with 95% confidence intervals (CI).

Results: Our meta-analysis included a total of 74 studies with a combined sample size of 7046 participants. The results of the analysis showed that acarbose resulted in a reduction in levels of TG (WMD = - 13.43 mg/dl, 95% CI: - 19.20, - 7.67; P < 0.001) and TC (WMD = - 1.93 mg/dl, 95% CI: - 3.71, - 0.15; P = 0.033), but did not affect other lipid markers. When conducting a nonlinear dose-response analysis, we found that acarbose was associated with an increase in levels of HDL (coefficients = 0.50, P = 0.012), with the highest increase observed at a dosage of 400 mg/d. Furthermore, our findings suggested a non-linear relationship between the duration of the intervention and TC (coefficients = - 18.00, P = 0.032), with a decline observed after 50 weeks of treatment.

Conclusion: The findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.

目的:血脂异常以甘油三酯(TG)、低密度脂蛋白(LDL)、总胆固醇(TC)水平升高和高密度脂蛋白(HDL)水平降低为特征,是心血管疾病(CVD)的主要危险因素。几项研究表明,阿卡波糖有改善血脂指标的潜力。然而,关于成人这个话题的研究结果却相互矛盾。因此,我们进行了一项全面的系统评价和荟萃分析,以评估阿卡波糖对血脂的影响。方法:采用随机效应法对资料进行合并,结果采用加权平均差(WMD), 95%可信区间(CI)。结果:我们的荟萃分析共纳入74项研究,总样本量为7046名参与者。分析结果显示,阿卡波糖导致TG水平降低(WMD = - 13.43 mg/dl, 95% CI: - 19.20, - 7.67;结论:阿卡波糖具有降低血清TG和TC水平的作用。然而,对低密度脂蛋白或高密度脂蛋白水平没有显著影响。
{"title":"The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials.","authors":"Mohsen Yousefi, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Samira Rastgoo, Reza Bagher, Alireza Khadem, Farideh Shiraseb, Omid Asbaghi","doi":"10.1186/s40360-023-00706-6","DOIUrl":"10.1186/s40360-023-00706-6","url":null,"abstract":"<p><strong>Purpose: </strong>Dyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density lipoprotein (HDL), is a major risk factor for cardiovascular diseases (CVD). Several studies have shown the potential of acarbose in improving serum lipid markers. However, there have been conflicting results on the topic in adults. Therefore, a comprehensive systematic review and meta-analysis was conducted to assess the impact of acarbose on lipid profiles.</p><p><strong>Methods: </strong>The random-effects approach was used to combine the data, and the results were provided as weighted mean difference (WMD) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Our meta-analysis included a total of 74 studies with a combined sample size of 7046 participants. The results of the analysis showed that acarbose resulted in a reduction in levels of TG (WMD = - 13.43 mg/dl, 95% CI: - 19.20, - 7.67; P < 0.001) and TC (WMD = - 1.93 mg/dl, 95% CI: - 3.71, - 0.15; P = 0.033), but did not affect other lipid markers. When conducting a nonlinear dose-response analysis, we found that acarbose was associated with an increase in levels of HDL (coefficients = 0.50, P = 0.012), with the highest increase observed at a dosage of 400 mg/d. Furthermore, our findings suggested a non-linear relationship between the duration of the intervention and TC (coefficients = - 18.00, P = 0.032), with a decline observed after 50 weeks of treatment.</p><p><strong>Conclusion: </strong>The findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"65"},"PeriodicalIF":2.9,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case-control study. 阿片类药物不良反应与基因多态性的相关性研究:一项病例-对照研究。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-21 DOI: 10.1186/s40360-023-00708-4
Jing Yang, Ying-Zi Sun, Qun-Fang Li, Zheng Fu, Yu-Yao Guan, Chao Song, Lei Zheng

Objective: Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.

Methods: Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.

Results: Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.

Conclusion: Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.

目的:阿片类药物引起的不良反应(adr)存在个体差异。我们的目的是探讨基因多态性与阿片类药物引起的不良反应之间的关系。方法:对阿片类药物引起的不良反应相关基因进行循证医学数据分析,选择靶基因。选取服用阿片类药物(吗啡、可待因、羟考酮)后出现不良反应的癌性疼痛患者60例作为实验组,服用阿片类药物后无不良反应的患者60例作为对照组。然后,我们使用聚合酶链反应(PCR)或原位杂交检测目标基因。结合年龄、性别、用药剂量、用药时间等临床资料,统计分析基因多态性对患者服用阿片类药物后不良反应的影响。结果:基于数据库检索和循证医学数据,我们确定了CYP2D6*10、CYP3A5*3、ABCB1和OPRM1作为检测的靶基因。统计分析结果显示,实验组与对照组基因型分布差异无统计学意义(p > 0.05)。然而,如果选择32例羟考酮后发生不良反应的患者和32例对照组进行比较,SPSS22.0和SNPStats遗传模型显示ABCB1 (062rs1045642) CT和TT基因型与不良反应的发生相关(p)。ABCB1 (062rs1045642)多态性与羟考酮引起的不良反应有关,且随着等位基因t的增加,不良反应的发生率更高,ABCB1多态性有望成为羟考酮不良反应的临床预测指标,ABCB1 (062rs1045642) CT和TT基因型患者发生严重不良反应的情况应引起重视。
{"title":"Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case-control study.","authors":"Jing Yang, Ying-Zi Sun, Qun-Fang Li, Zheng Fu, Yu-Yao Guan, Chao Song, Lei Zheng","doi":"10.1186/s40360-023-00708-4","DOIUrl":"10.1186/s40360-023-00708-4","url":null,"abstract":"<p><strong>Objective: </strong>Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.</p><p><strong>Methods: </strong>Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.</p><p><strong>Results: </strong>Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.</p><p><strong>Conclusion: </strong>Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"64"},"PeriodicalIF":2.9,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bisdemethoxycurcumin alleviates LPS-induced acute lung injury via activating AMPKα pathway. 双去甲氧基姜黄素通过激活AMPKα通路减轻lps诱导的急性肺损伤。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-20 DOI: 10.1186/s40360-023-00698-3
Huifang Li, Qi Zou, Xueming Wang

Objective: Inflammation and oxidative stress contribute to the pathogenesis of acute lung injury (ALI), and subsequently result in rapid deterioration in health. Considering the indispensable role of bisdemethoxycurcumin (BDMC) in inflammation and oxidative stress, the present study aims to examine the effect of BDMC on sepsis-related ALI.

Methods: C57BL/6 mice were administered with BDMC (100 mg/kg) or an equal volume of vehicle, and then injected with lipopolysaccharides (LPS) to induce ALI. We assessed the parameters of lung injury, inflammatory response and oxidative stress in lung tissues. Consistently, the macrophages with or without BDMC treatment were exposed to LPS to verify the effect of BDMC in vitro.

Results: BDMC suppressed LPS-induced lung injury, inflammation and oxidative stress in vivo and in vitro. Mechanistically, BDMC increased the phosphorylation of AMPKα in response to LPS stimulation, and AMPK inhibition with Compound C almost completely blunted the protective effect of BDMC in LPS-treated mice and macrophages. Moreover, we demonstrated that BDMC activated AMPKα via the cAMP/Epac pathway.

Conclusion: Our study identifies the protective effect of BDMC against LPS-induced ALI, and the underlying mechanism may be related to the activation of cAMP/Epac/AMPKα signaling pathway.

目的:炎症和氧化应激参与急性肺损伤(ALI)的发病机制,并导致健康状况迅速恶化。考虑到双去甲氧基姜黄素(BDMC)在炎症和氧化应激中不可或缺的作用,本研究旨在探讨BDMC对败血症相关性ALI的影响。方法:给C57BL/6小鼠灌胃BDMC (100 mg/kg)或等体积的载药,再注射脂多糖(LPS)诱导ALI。我们评估肺损伤、炎症反应和肺组织氧化应激的参数。与此一致的是,将处理过或未处理过BDMC的巨噬细胞暴露于LPS,以验证BDMC在体外的作用。结果:BDMC在体内外均能抑制lps诱导的肺损伤、炎症和氧化应激。在机制上,BDMC增加了AMPKα对LPS刺激的磷酸化反应,化合物C抑制AMPK几乎完全减弱了BDMC对LPS处理小鼠和巨噬细胞的保护作用。此外,我们证明了BDMC通过cAMP/Epac途径激活AMPKα。结论:本研究确定了BDMC对lps诱导的ALI的保护作用,其机制可能与激活cAMP/Epac/AMPKα信号通路有关。
{"title":"Bisdemethoxycurcumin alleviates LPS-induced acute lung injury via activating AMPKα pathway.","authors":"Huifang Li, Qi Zou, Xueming Wang","doi":"10.1186/s40360-023-00698-3","DOIUrl":"10.1186/s40360-023-00698-3","url":null,"abstract":"<p><strong>Objective: </strong>Inflammation and oxidative stress contribute to the pathogenesis of acute lung injury (ALI), and subsequently result in rapid deterioration in health. Considering the indispensable role of bisdemethoxycurcumin (BDMC) in inflammation and oxidative stress, the present study aims to examine the effect of BDMC on sepsis-related ALI.</p><p><strong>Methods: </strong>C57BL/6 mice were administered with BDMC (100 mg/kg) or an equal volume of vehicle, and then injected with lipopolysaccharides (LPS) to induce ALI. We assessed the parameters of lung injury, inflammatory response and oxidative stress in lung tissues. Consistently, the macrophages with or without BDMC treatment were exposed to LPS to verify the effect of BDMC in vitro.</p><p><strong>Results: </strong>BDMC suppressed LPS-induced lung injury, inflammation and oxidative stress in vivo and in vitro. Mechanistically, BDMC increased the phosphorylation of AMPKα in response to LPS stimulation, and AMPK inhibition with Compound C almost completely blunted the protective effect of BDMC in LPS-treated mice and macrophages. Moreover, we demonstrated that BDMC activated AMPKα via the cAMP/Epac pathway.</p><p><strong>Conclusion: </strong>Our study identifies the protective effect of BDMC against LPS-induced ALI, and the underlying mechanism may be related to the activation of cAMP/Epac/AMPKα signaling pathway.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"63"},"PeriodicalIF":2.9,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). FDA不良事件报告系统(FAERS)中与帕妥珠单抗相关的不良事件的不成比例分析。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-13 DOI: 10.1186/s40360-023-00702-w
Shu-Peng Zou, Hai-Yun Yang, Meng-Ling Ouyang, Qian Cheng, Xuan Shi, Ming-Hui Sun

Background: Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present.

Methods: In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs.

Results: From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC025 (information component). The potential strong signals (IC025 > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy.

Conclusion: Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases.

背景:帕妥珠单抗被广泛用于治疗HER2 +乳腺癌。但它在现实世界中的安全性应该受到持续监控。因此,我们基于FDA不良事件报告系统(FAERS)的相关不良事件(ae),通过药物警戒分析来评估帕妥珠单抗的安全性,并确定是否存在潜在或不确定的不良事件。方法:在歧化分析中,采用四种算法检测2012年至2022年FAERS中帕妥珠单抗的信号。此外,我们还使用MYSQL 8.0、Navicat Premium 15和Microsoft EXCEL 2019分析了帕妥珠单抗的潜在和高ror(报告优势比)信号。我们还收集了帕妥珠单抗相关ae的发病时间。结果:2012年1月至2022年12月,FAERS数据库共报告了39,190,598例ae,其中14,707例ae将帕妥珠单抗列为“主要疑似(PS)”药物。总共保留了符合四种算法的115个(46个潜在的)显著歧化首选项(PTs)。最后,我们检测到pertuzumab诱导的ae发生在12个器官系统中。对于帕妥珠单抗,发现了意外且显著的ae PTs,包括但不限于以下PTs:血液毒性、心脏毒性、心肌病、二尖瓣功能不全、心动过速、肠穿孔、痔疮、丹毒、脱水、肺炎、皮肤毒性、甲状瘤、发绀和循环衰竭。根据IC025(信息分量),我们发现有9个强信号(5个安全隐患信号)和68个中强度信号(21个安全隐患信号)。潜在的强信号(IC025 > 3.0)为骨髓抑制、心脏毒性、心功能障碍、射血分数下降、间质性肺疾病和软骨发育。排除未报告或不合理的发病时间报告,2016例ae报告的发病时间和中位发病时间为117天(4,96),为中位数(Q1, Q3)。值得注意的是,大多数ae (n = 1133, 56%)和心脏相关事件(n = 405, 53%)都发生在帕妥珠单抗治疗后一个月内。结论:FAERS数据分析确定了与帕妥珠单抗相关的ae,我们的研究结果支持持续的临床监测、药物警戒和进一步的帕妥珠单抗研究。发现帕妥珠单抗与一些潜在不良事件之间存在显著关联,应谨慎对待。我们必须重视帕妥珠单抗治疗后的第一个月,并准备应急措施,特别是对老年人和心血管疾病患者。
{"title":"A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS).","authors":"Shu-Peng Zou, Hai-Yun Yang, Meng-Ling Ouyang, Qian Cheng, Xuan Shi, Ming-Hui Sun","doi":"10.1186/s40360-023-00702-w","DOIUrl":"10.1186/s40360-023-00702-w","url":null,"abstract":"<p><strong>Background: </strong>Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present.</p><p><strong>Methods: </strong>In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs.</p><p><strong>Results: </strong>From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC<sub>025</sub> (information component). The potential strong signals (IC<sub>025</sub> > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy.</p><p><strong>Conclusion: </strong>Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"62"},"PeriodicalIF":2.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
In vitro evaluation of cell viability and expression profile of growth factors in mouse Sertoli cells exposed to Delta-9-tetrahydrocannabinol: a mechanistic insight into the cannabinoid-induced testicular toxicity. 暴露于Delta-9-四氢大麻素的小鼠支持细胞中细胞活力和生长因子表达谱的体外评估:大麻素诱导睾丸毒性的机制研究。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-09 DOI: 10.1186/s40360-023-00704-8
Shadi Mohammadpour-Asl, Shiva Roshan-Milani, Amin Abdollahzade Fard, Ali Golchin

The potentially adverse effects of cannabis (marijuana), a common leisure compound, on male reproductive performance are a reason for concern. δ-9-tetrahydrocannabinol (THC), the primary active component of marijuana alters testicular cells' proliferation and function which affects male fertility and causes testicular cells dysfunction and apoptosis. The main objective of this study was to investigate the possible mechanism underlying the toxic effects of THC with a mechanistic insight into Sertoli cell-based reproductive dysfunction. The Mus musculus Sertoli cell line (TM4) was cultured and exposed to different concentrations of THC and, MTT (3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was then performed for evaluating cell viability. The expression of caspase-3 gene and genes related to growth factors were analyzed by real-time RT-PCR. Western blotting was performed for evaluating protein expression level. THC concentration-dependently decreased the TM4 viability with a significant effect starting at concentration of 1 μM and reaching about 75% of the control level at the concentration of 50 μM (IC25). Moreover, caspase-3 mRNA expression levels significantly increased while growth factors mRNA levels decreased in THC-exposed cells compared to unexposed cells. There was also a significant reduction in related protein levels in THC group. Administration of the THC promotes cytotoxic and apoptotic effects on TM4 cells partly through down-regulation of growth factors expression. Increased apoptosis, over expression of caspase-3, and down-regulation of growth factors expression in Sertoli cells exposed to THC may be a reflection of THC-induced testicular toxicity, which may be partly involved in infertility associated with marijuana smoking or medical cannabis use.

大麻(大麻)是一种常见的休闲化合物,对男性生殖能力的潜在不利影响令人担忧。大麻的主要活性成分δ-9-四氢大麻酚(THC)会改变睾丸细胞的增殖和功能,从而影响男性生育能力,并导致睾丸细胞功能障碍和凋亡。本研究的主要目的是通过对支持细胞生殖功能障碍的机制深入研究四氢大麻酚毒性作用的可能机制。培养支持肌细胞系(TM4)并将其暴露于不同浓度的THC,然后进行MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物)测定以评估细胞活力。实时RT-PCR检测半胱氨酸蛋白酶-3基因及生长因子相关基因的表达。进行蛋白质印迹以评估蛋白质表达水平。THC浓度依赖性地降低TM4的活力,从1 μM,浓度为50时达到对照水平的75%左右 μM(IC25)。此外,与未暴露的细胞相比,THC暴露的细胞中胱天蛋白酶-3 mRNA表达水平显著增加,而生长因子mRNA水平降低。THC组的相关蛋白质水平也显著降低。THC的施用部分通过下调生长因子的表达来促进对TM4细胞的细胞毒性和凋亡作用。在暴露于四氢大麻酚的支持细胞中,细胞凋亡增加、胱天蛋白酶-3过度表达和生长因子表达下调可能反映了四氢大麻酸诱导的睾丸毒性,这可能在一定程度上与吸食大麻或医用大麻相关的不孕有关。
{"title":"In vitro evaluation of cell viability and expression profile of growth factors in mouse Sertoli cells exposed to Delta-9-tetrahydrocannabinol: a mechanistic insight into the cannabinoid-induced testicular toxicity.","authors":"Shadi Mohammadpour-Asl, Shiva Roshan-Milani, Amin Abdollahzade Fard, Ali Golchin","doi":"10.1186/s40360-023-00704-8","DOIUrl":"10.1186/s40360-023-00704-8","url":null,"abstract":"<p><p>The potentially adverse effects of cannabis (marijuana), a common leisure compound, on male reproductive performance are a reason for concern. δ-9-tetrahydrocannabinol (THC), the primary active component of marijuana alters testicular cells' proliferation and function which affects male fertility and causes testicular cells dysfunction and apoptosis. The main objective of this study was to investigate the possible mechanism underlying the toxic effects of THC with a mechanistic insight into Sertoli cell-based reproductive dysfunction. The Mus musculus Sertoli cell line (TM4) was cultured and exposed to different concentrations of THC and, MTT (3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was then performed for evaluating cell viability. The expression of caspase-3 gene and genes related to growth factors were analyzed by real-time RT-PCR. Western blotting was performed for evaluating protein expression level. THC concentration-dependently decreased the TM4 viability with a significant effect starting at concentration of 1 μM and reaching about 75% of the control level at the concentration of 50 μM (IC<sub>25</sub>). Moreover, caspase-3 mRNA expression levels significantly increased while growth factors mRNA levels decreased in THC-exposed cells compared to unexposed cells. There was also a significant reduction in related protein levels in THC group. Administration of the THC promotes cytotoxic and apoptotic effects on TM4 cells partly through down-regulation of growth factors expression. Increased apoptosis, over expression of caspase-3, and down-regulation of growth factors expression in Sertoli cells exposed to THC may be a reflection of THC-induced testicular toxicity, which may be partly involved in infertility associated with marijuana smoking or medical cannabis use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"61"},"PeriodicalIF":2.9,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10636832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sericin alleviates motor dysfunction by modulating inflammation and TrkB/BDNF signaling pathway in the rotenone-induced Parkinson's disease model. 在鱼藤酮诱导的帕金森病模型中,丝氨酸通过调节炎症和TrkB/BDNF信号通路减轻运动功能障碍。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-07 DOI: 10.1186/s40360-023-00703-9
Zahra Salari, Ghorbangol Ashabi, Ali Fartoosi, Ahmad Fartoosi, Marjan Shariatpanahi, Mehdi Aghsami, Hamed Montazeri, Afshin Kheradmand

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of nigrostriatal dopaminergic neurons and movement impairment. Based on theories, neuroinflammatory processes may be vital in the etiology of PD and other neurodegenerative diseases. Reports show that rotenone has neurotoxic, inflammatory, and motor impairment effects in PD. Sericin is a natural polymer with effective properties, such as neuroprotective and anti-inflammatory. Therefore, this study aimed to examine the effects of sericin administration on motor dysfunction by modulating inflammation and tyrosine kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathway in the rotenone-induced PD model.

Methods: Wistar male rats (3-months-old) were treated with rotenone (2 mg/kg every 48 h for 30 days) to induce a rotenone-induced PD model. Also, sericin was administered orally at dose of 200 mg/kg every 48 h for 30 days. Rotarod and bar tests were performed for motor dysfunction. The protein levels of BDNF, c-fos, TrkB, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6) and catalase activity were evaluated in the striatum area.

Results: Results showed that sericin increased latent time in the rotarod test and decreased the time staying on the pole in the bar test compared to the PD group (P < 0.001 for both tests). Moreover, sericin treatments decreased TNF-α (P < 0.001) and IL-6 (P < 0.001) concentration levels and enhanced the levels of BDNF (P < 0.001), c-fos (P < 0.001), TrkB (P < 0.001) proteins and catalase activity (P < 0.05) in the striatum area compared to the PD group.

Conclusion: These results support a protective benefit of sericin therapy in a rotenone-induced PD paradigm by reducing motor impairment, inflammatory response, and disruption of the TrkB/BDNF signaling pathway.

背景:帕金森病(PD)是一种以黑质纹状体多巴胺能神经元变性和运动障碍为特征的进行性神经退行性疾病。根据理论,神经炎症过程可能在帕金森病和其他神经退行性疾病的病因中至关重要。据报道,鱼藤酮对帕金森病具有神经毒性、炎症和运动损伤作用。丝氨酸是一种具有神经保护和抗炎等有效特性的天然聚合物。因此,本研究旨在通过调节鱼藤酮诱导的帕金森病模型中的炎症和酪氨酸激酶B/脑源性神经营养因子(TrkB/BDNF)通路,检验丝胶给药对运动功能障碍的影响。方法:Wistar雄性大鼠(3个月大)用鱼藤酮(2mg/kg,每48小时一次,持续30天)诱导鱼藤酮诱导的PD模型。此外,丝胶以200mg/kg的剂量每48小时口服给药30天。针对运动功能障碍进行了Rotarod和bar测试。检测纹状体区BDNF、c-fos、TrkB、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和过氧化氢酶活性的蛋白水平。结果:与PD组相比,丝胶在旋转棒试验中增加了潜伏时间,在棒试验中减少了在杆上停留的时间(P 结论:这些结果支持丝胶治疗在鱼藤酮诱导的PD模型中的保护作用,通过减少运动损伤、炎症反应和TrkB/BDNF信号通路的破坏。
{"title":"Sericin alleviates motor dysfunction by modulating inflammation and TrkB/BDNF signaling pathway in the rotenone-induced Parkinson's disease model.","authors":"Zahra Salari, Ghorbangol Ashabi, Ali Fartoosi, Ahmad Fartoosi, Marjan Shariatpanahi, Mehdi Aghsami, Hamed Montazeri, Afshin Kheradmand","doi":"10.1186/s40360-023-00703-9","DOIUrl":"10.1186/s40360-023-00703-9","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of nigrostriatal dopaminergic neurons and movement impairment. Based on theories, neuroinflammatory processes may be vital in the etiology of PD and other neurodegenerative diseases. Reports show that rotenone has neurotoxic, inflammatory, and motor impairment effects in PD. Sericin is a natural polymer with effective properties, such as neuroprotective and anti-inflammatory. Therefore, this study aimed to examine the effects of sericin administration on motor dysfunction by modulating inflammation and tyrosine kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathway in the rotenone-induced PD model.</p><p><strong>Methods: </strong>Wistar male rats (3-months-old) were treated with rotenone (2 mg/kg every 48 h for 30 days) to induce a rotenone-induced PD model. Also, sericin was administered orally at dose of 200 mg/kg every 48 h for 30 days. Rotarod and bar tests were performed for motor dysfunction. The protein levels of BDNF, c-fos, TrkB, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6) and catalase activity were evaluated in the striatum area.</p><p><strong>Results: </strong>Results showed that sericin increased latent time in the rotarod test and decreased the time staying on the pole in the bar test compared to the PD group (P < 0.001 for both tests). Moreover, sericin treatments decreased TNF-α (P < 0.001) and IL-6 (P < 0.001) concentration levels and enhanced the levels of BDNF (P < 0.001), c-fos (P < 0.001), TrkB (P < 0.001) proteins and catalase activity (P < 0.05) in the striatum area compared to the PD group.</p><p><strong>Conclusion: </strong>These results support a protective benefit of sericin therapy in a rotenone-induced PD paradigm by reducing motor impairment, inflammatory response, and disruption of the TrkB/BDNF signaling pathway.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"60"},"PeriodicalIF":2.9,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of intravenous N acetylcysteine as an adjuvant therapy in the treatment of acute aluminum phosphide Poisoning: a systematic review and meta-analysis. 静脉注射N-乙酰半胱氨酸辅助治疗急性磷化铝中毒的疗效:系统综述和荟萃分析。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-03 DOI: 10.1186/s40360-023-00699-2
Heba Othman Shaker, Omar El Sayed Rageh, Maged Alnajar, Nesreen Fares Alshamaly, Walaa Abdelfattah Abdelmaged, Mohamed Abd-ElGawad

Background: Aluminum phosphide toxicity is a serious problem in many countries. Unfortunately, there is no specific antidote. N-acetylcysteine has been used in some studies as adjuvant therapy depending on to its antioxidant properties. We hypothesized that IV N-acetylcysteine is effective in reducing mortality rate compared to supportive treatment alone.

Methods: We searched in PubMed, Scopus, Web of Science, and Cochrane Library databases. We only included randomized controlled trials that assessed the efficacy of IV N-acetylcysteine and supportive treatment versus supportive treatment alone in acute aluminum phosphide poisoning. Four investigators independently screened the studies' results and designed the data extraction sheet. The primary and secondary outcomes were mortality and the need for mechanical ventilation rates. Random effects estimators with weights were used to result in the pooled risk ratios.

Results: We included four randomized controlled trials with 177 patients. 91 patients were distributed in N-acetylcysteine group and 86 patients in the control group. Mortality rates in N-acetylcysteine group and in the control group were 43.95% 66.27% respectively. There was a statistically significant reduction in mortality rate after leave out test (pooled risk ratio, 0.5; 95% confidence interval, 0.32-0.77). Regarding the need for mechanical ventilation, it was measured only in three RCTs. It was assessed in 67 patients in N-acetylcysteine group and 60 patients in the control group. 24 patients were ventilated in N-acetylcysteine group (35.8%) and 29 patients in the control group (48.3%). But it was statistically nonsignificant (pooled risk ratio, 0.71; 95% confidence interval, 0.48-1.04).

Conclusion: Our meta-analysis revealed that IV N-acetylcysteine may be effective in reducing mortality of severe aluminum phosphide poisoning cases.

Trial registration: Registration number in Prospero CRD42022375344 on 25 NOVEMBER 2022, retrospectively registered.

背景:磷化铝的毒性在许多国家都是一个严重的问题。不幸的是,没有特效药。N-乙酰半胱氨酸由于其抗氧化特性,在一些研究中被用作辅助治疗。我们假设静脉注射N-乙酰半胱氨酸与单独的支持性治疗相比能有效降低死亡率。方法:检索PubMed、Scopus、Web of Science和Cochrane Library数据库。我们只纳入了随机对照试验,这些试验评估了静脉注射N-乙酰半胱氨酸和支持性治疗与单独支持性治疗急性磷化铝中毒的疗效。四名研究人员对研究结果进行了独立筛选,并设计了数据提取表。主要和次要结果是死亡率和需要机械通气率。使用具有权重的随机效应估计量来得出合并风险比。结果:我们纳入了四项随机对照试验,共177名患者。N-乙酰半胱氨酸组91例,对照组86例。N-乙酰半胱氨酸组和对照组的死亡率分别为43.95%和66.27%。遗漏试验后死亡率有统计学意义的降低(合并风险比为0.5;95%置信区间为0.32-0.77)。关于机械通气的必要性,仅在三项随机对照试验中进行了测量。在N-乙酰半胱氨酸组的67名患者和对照组的60名患者中进行了评估。N-乙酰半胱氨酸组24例(35.8%)和对照组29例(48.3%)进行了通气。但这在统计学上并不显著(合并风险比为0.71;95%置信区间为0.48-1.04)。结论:我们的荟萃分析显示,静脉注射N-乙酰半胱氨酸可能有效降低严重磷化铝中毒病例的死亡率。试验注册:2022年11月25日在Prospero CRD42022375344中的注册号,追溯注册。
{"title":"Efficacy of intravenous N acetylcysteine as an adjuvant therapy in the treatment of acute aluminum phosphide Poisoning: a systematic review and meta-analysis.","authors":"Heba Othman Shaker,&nbsp;Omar El Sayed Rageh,&nbsp;Maged Alnajar,&nbsp;Nesreen Fares Alshamaly,&nbsp;Walaa Abdelfattah Abdelmaged,&nbsp;Mohamed Abd-ElGawad","doi":"10.1186/s40360-023-00699-2","DOIUrl":"https://doi.org/10.1186/s40360-023-00699-2","url":null,"abstract":"<p><strong>Background: </strong>Aluminum phosphide toxicity is a serious problem in many countries. Unfortunately, there is no specific antidote. N-acetylcysteine has been used in some studies as adjuvant therapy depending on to its antioxidant properties. We hypothesized that IV N-acetylcysteine is effective in reducing mortality rate compared to supportive treatment alone.</p><p><strong>Methods: </strong>We searched in PubMed, Scopus, Web of Science, and Cochrane Library databases. We only included randomized controlled trials that assessed the efficacy of IV N-acetylcysteine and supportive treatment versus supportive treatment alone in acute aluminum phosphide poisoning. Four investigators independently screened the studies' results and designed the data extraction sheet. The primary and secondary outcomes were mortality and the need for mechanical ventilation rates. Random effects estimators with weights were used to result in the pooled risk ratios.</p><p><strong>Results: </strong>We included four randomized controlled trials with 177 patients. 91 patients were distributed in N-acetylcysteine group and 86 patients in the control group. Mortality rates in N-acetylcysteine group and in the control group were 43.95% 66.27% respectively. There was a statistically significant reduction in mortality rate after leave out test (pooled risk ratio, 0.5; 95% confidence interval, 0.32-0.77). Regarding the need for mechanical ventilation, it was measured only in three RCTs. It was assessed in 67 patients in N-acetylcysteine group and 60 patients in the control group. 24 patients were ventilated in N-acetylcysteine group (35.8%) and 29 patients in the control group (48.3%). But it was statistically nonsignificant (pooled risk ratio, 0.71; 95% confidence interval, 0.48-1.04).</p><p><strong>Conclusion: </strong>Our meta-analysis revealed that IV N-acetylcysteine may be effective in reducing mortality of severe aluminum phosphide poisoning cases.</p><p><strong>Trial registration: </strong>Registration number in Prospero CRD42022375344 on 25 NOVEMBER 2022, retrospectively registered.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"59"},"PeriodicalIF":2.9,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
BMC Pharmacology & Toxicology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1