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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 Medicine 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。
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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 Medicine 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。
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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 Medicine 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。
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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 Medicine 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":null,"pages":null},"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
GHB toxicokinetics and renal monocarboxylate transporter expression are influenced by the estrus cycle in rats. GHB毒代动力学和肾脏单羧酸转运蛋白的表达受大鼠发情周期的影响。
IF 2.9 3区 医学 Q2 Medicine Pub Date : 2023-11-02 DOI: 10.1186/s40360-023-00700-y
Hao Wei, Jieyun Cao, Tyler Fallert, Su Yeo, Melanie A Felmlee

Background: The illicit use and abuse of gamma-hydroxybutyric acid (GHB) occurs due to its sedative/hypnotic and euphoric effects. Currently, there are no clinically available therapies to treat GHB overdose, and care focuses on symptom treatment until the drug is eliminated from the body. Proton- and sodium-dependent monocarboxylate transporters (MCTs (SLC16A) and SMCTs (SLC5A)) transport and mediate the renal clearance and distribution of GHB. Previously, it has been shown that MCT expression is regulated by sex hormones in the liver, skeletal muscle and Sertoli cells. The focus of the current study is to evaluate GHB toxicokinetics and renal monocarboxylate transporter expression over the estrus cycle in females, and in the absence of male and female sex hormones.

Methods: GHB toxicokinetics and renal transporter expression of MCT1, SMCT1 and CD147 were evaluated in females over the estrus cycle, and in ovariectomized (OVX) female, male and castrated (CST) male rats. GHB was administered iv bolus (600 and 1000 mg/kg) and plasma and urine samples were collected for six hours post-dose. GHB concentrations were quantified using a validated LC/MS/MS assay. Transporter mRNA and protein expression was quantified by qPCR and Western Blot.

Results: GHB renal clearance and AUC varied between sexes and over the estrus cycle in females with higher renal clearance and a lower AUC in proestrus females as compared to males (intact and CST), and OVX females. We demonstrated that renal MCT1 membrane expression varies over the estrus cycle, with the lowest expression observed in proestrus females, which is consistent with the observed changes in GHB renal clearance.

Conclusions: Our results suggest that females may be less susceptible to GHB-induced toxicity due to decreased exposure resulting from increased renal clearance, as a result of decreased renal MCT1 expression.

背景:γ-羟基丁酸(GHB)的非法使用和滥用是由于其镇静/催眠和欣快作用。目前,没有临床上可用的治疗GHB过量的疗法,护理重点是症状治疗,直到药物从体内清除。质子和钠依赖性单羧酸盐转运蛋白(MCTs(SLC16A)和SMCT(SLC5A))转运并介导GHB的肾脏清除和分布。此前,已经表明MCT的表达受到肝脏、骨骼肌和支持细胞中性激素的调节。当前研究的重点是评估雌性发情周期中以及在缺乏雄性和雌性性激素的情况下GHB毒代动力学和肾脏单羧酸转运蛋白的表达。方法:在发情期雌性大鼠以及去卵巢(OVX)雌性、雄性和去势(CST)雄性大鼠中,评估GHB毒代动力学和MCT1、SMCT1和CD147的肾转运蛋白表达。GHB静脉推注(600和1000mg/kg),并在给药后6小时内收集血浆和尿液样本。GHB浓度使用经验证的LC/MS/MS测定法进行定量。通过qPCR和Western Blot对转运蛋白mRNA和蛋白表达进行定量。结果:与雄性(完整和CST)和OVX雌性相比,雌性发情前期的GHB肾脏清除率和AUC较高,而AUC较低,在不同性别和整个发情周期内,GHB肾脏清理率和AUC各不相同。我们证明,肾脏MCT1膜表达在发情周期内变化,在发情前期雌性中观察到的表达最低,这与观察到的GHB肾脏清除率的变化一致。结论:我们的研究结果表明,女性可能不太容易受到GHB诱导的毒性的影响,因为肾脏MCT1表达减少,导致肾脏清除率增加,暴露量减少。
{"title":"GHB toxicokinetics and renal monocarboxylate transporter expression are influenced by the estrus cycle in rats.","authors":"Hao Wei,&nbsp;Jieyun Cao,&nbsp;Tyler Fallert,&nbsp;Su Yeo,&nbsp;Melanie A Felmlee","doi":"10.1186/s40360-023-00700-y","DOIUrl":"10.1186/s40360-023-00700-y","url":null,"abstract":"<p><strong>Background: </strong>The illicit use and abuse of gamma-hydroxybutyric acid (GHB) occurs due to its sedative/hypnotic and euphoric effects. Currently, there are no clinically available therapies to treat GHB overdose, and care focuses on symptom treatment until the drug is eliminated from the body. Proton- and sodium-dependent monocarboxylate transporters (MCTs (SLC16A) and SMCTs (SLC5A)) transport and mediate the renal clearance and distribution of GHB. Previously, it has been shown that MCT expression is regulated by sex hormones in the liver, skeletal muscle and Sertoli cells. The focus of the current study is to evaluate GHB toxicokinetics and renal monocarboxylate transporter expression over the estrus cycle in females, and in the absence of male and female sex hormones.</p><p><strong>Methods: </strong>GHB toxicokinetics and renal transporter expression of MCT1, SMCT1 and CD147 were evaluated in females over the estrus cycle, and in ovariectomized (OVX) female, male and castrated (CST) male rats. GHB was administered iv bolus (600 and 1000 mg/kg) and plasma and urine samples were collected for six hours post-dose. GHB concentrations were quantified using a validated LC/MS/MS assay. Transporter mRNA and protein expression was quantified by qPCR and Western Blot.</p><p><strong>Results: </strong>GHB renal clearance and AUC varied between sexes and over the estrus cycle in females with higher renal clearance and a lower AUC in proestrus females as compared to males (intact and CST), and OVX females. We demonstrated that renal MCT1 membrane expression varies over the estrus cycle, with the lowest expression observed in proestrus females, which is consistent with the observed changes in GHB renal clearance.</p><p><strong>Conclusions: </strong>Our results suggest that females may be less susceptible to GHB-induced toxicity due to decreased exposure resulting from increased renal clearance, as a result of decreased renal MCT1 expression.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420467","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
Correction: Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells. 更正:胰高血糖素样肽受体激动剂可减轻大鼠系膜细胞中晚期糖基化终产物诱导的炎症。
IF 2.9 3区 医学 Q2 Medicine Pub Date : 2023-10-27 DOI: 10.1186/s40360-023-00688-5
Jui-Ting Chang, Yao-Jen Liang, Chia-Yu Hsu, Chao-Yi Chen, Po-Jung Chen, Yi-Feng Yang, Yen-Lin Chen, Dee Pei, Jin-Biou Chang, Jyh-Gang Leu
{"title":"Correction: Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells.","authors":"Jui-Ting Chang,&nbsp;Yao-Jen Liang,&nbsp;Chia-Yu Hsu,&nbsp;Chao-Yi Chen,&nbsp;Po-Jung Chen,&nbsp;Yi-Feng Yang,&nbsp;Yen-Lin Chen,&nbsp;Dee Pei,&nbsp;Jin-Biou Chang,&nbsp;Jyh-Gang Leu","doi":"10.1186/s40360-023-00688-5","DOIUrl":"10.1186/s40360-023-00688-5","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61560773","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
Oxidative stress induction by narasin augments doxorubicin's efficacy in osteosarcoma. narasin的氧化应激诱导增强了阿霉素治疗骨肉瘤的疗效。
IF 2.9 3区 医学 Q2 Medicine Pub Date : 2023-10-20 DOI: 10.1186/s40360-023-00695-6
Zhaoming Han, Juguang Yang, Ping Wang, Feng Bian, Jiguang Jia

Complications and fata toxicity induced by chemotherapy are the main challenge for clinical management of osteosarcoma. The identification of agents that can augment the efficacy of chemotherapy at lower doses may represent an alternative therapeutic strategy. Narasin is a polyether antibiotic widely used in veterinary medicine. In this study, we show that narasin is active against osteosarcoma cells at the same concentrations that are less toxic to normal cells. This effect is achieved by growth inhibition and apoptosis induction, which is mediated by oxidative stress and damage, and mitochondrial dysfunction. The antioxidant N-acetyl-l-cysteine (NAC) abolishes the anti-osteosarcoma activity. Importantly, narasin significantly augments doxorubicin's efficacy in both osteosarcoma cell culturing system and subcutaneous implantation mouse model. The combination of narasin and doxorubicin at non-toxic doses completely arrests osteosarcoma growth in mice. Our results suggest that the concurrent administration of doxorubicin and narasin could present a viable alternative therapeutic approach for osteosarcoma.

化疗引起的并发症和脂肪毒性是骨肉瘤临床治疗的主要挑战。鉴定能够在较低剂量下增强化疗疗效的药物可能代表一种替代治疗策略。Narasin是一种广泛应用于兽医学的聚醚类抗生素。在这项研究中,我们发现narasin在对正常细胞毒性较小的相同浓度下对骨肉瘤细胞具有活性。这种作用是通过氧化应激和损伤以及线粒体功能障碍介导的生长抑制和细胞凋亡诱导来实现的。抗氧化剂N-乙酰基-1-半胱氨酸(NAC)消除了抗骨肉瘤的活性。重要的是,narasin显著增强了阿霉素在骨肉瘤细胞培养系统和皮下植入小鼠模型中的疗效。narasin和阿霉素在无毒剂量下的组合完全阻止了小鼠骨肉瘤的生长。我们的研究结果表明,同时给予阿霉素和纳拉辛可以为骨肉瘤提供一种可行的替代治疗方法。
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引用次数: 0
Correction: Core decompression combined with local DFO administration loaded on polylactic glycolic acid scaffolds for the treatment of osteonecrosis of the femoral head: a pilot study. 更正:核心减压联合负载在聚乳酸-乙醇酸支架上的局部DFO给药治疗股骨头坏死:一项初步研究。
IF 2.9 3区 医学 Q2 Medicine Pub Date : 2023-10-17 DOI: 10.1186/s40360-023-00691-w
Kaveh Gharanizadeh, Ali Mohammad Sharifi, Hamed Tayyebi, Razieh Heidari, Shayan Amiri, Sajad Noorigaravand
{"title":"Correction: Core decompression combined with local DFO administration loaded on polylactic glycolic acid scaffolds for the treatment of osteonecrosis of the femoral head: a pilot study.","authors":"Kaveh Gharanizadeh, Ali Mohammad Sharifi, Hamed Tayyebi, Razieh Heidari, Shayan Amiri, Sajad Noorigaravand","doi":"10.1186/s40360-023-00691-w","DOIUrl":"10.1186/s40360-023-00691-w","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232192","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
Acute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats. AT-533和AT-533凝胶在Sprague-Dawley大鼠中的急性毒理学评价。
IF 2.9 3区 医学 Q2 Medicine Pub Date : 2023-10-13 DOI: 10.1186/s40360-023-00696-5
Lishan Zhong, Yanting Wu, Chen Huang, Kaisheng Liu, Cui-Fang Ye, Zhe Ren, Yifei Wang

Background: AT-533 is a novel heat shock protein 90 inhibitor that exerting anti-inflammatory, antiviral, and antitumor efficacy. Furthermore, the gel made of AT-533 as raw material named AT-533 gel has the function of repairing keratitis and dermatitis caused by herpes virus infection. However, the acute safety evaluation of AT-533 and AT-533 gel has not been conducted.

Methods and results: Herein, we performed acute toxicological studies of AT-533 and AT-533 gel in Sprague-Dawley rats. Fifteen-day acute toxicity study of AT-533 was conducted in both male and female Sprague-Dawley rats at doses of 5, 50, 250 and 500 mg/kg and AT-533 gel at 5 g/kg in the study. During experiment, food consumption and mortality were observed and body weight, hematology, serum biochemistry and histopathological assessment of rats were carried out. No abnormal changes were observed in rats percutaneously treated with AT-533 at 5 mg/kg and 50 mg/kg and AT-533 gel. However, loss of appetite and body weight, adverse reactions, toxicologically relevant alterations in hematology and biochemistry were found in rats percutaneously treated with AT-533 at 250 mg/kg and 500 mg/kg during 15-day acute dermic toxicity study.

Conclusions: The aforementioned results suggested that the LD50 of AT-533 is 228.382 mg/kg and the LD50 of AT-533 gel is greater than 5 g/kg. These findings indicated that AT-533 is non-toxic in rats when the dose less than 50 mg/kg and AT-533 gel can be considered a gel with no toxicity at doses less than 5 g/kg.

背景:AT-533是一种新型的热休克蛋白90抑制剂,具有抗炎、抗病毒和抗肿瘤的作用。此外,以AT-533为原料制成的名为AT-533凝胶的凝胶具有修复疱疹病毒感染引起的角膜炎和皮炎的功能。然而,尚未对AT-533和AT-533凝胶进行急性安全性评估。方法和结果:本文对AT-533和AT-533凝胶在Sprague-Dawley大鼠体内进行了急性毒理学研究。AT-533的15天急性毒性研究在雄性和雌性Sprague-Dawley大鼠中进行,剂量分别为5、50、250和500 mg/kg,研究中AT-533凝胶的剂量为5 g/kg。实验期间,观察大鼠的进食量和死亡率,并对大鼠的体重、血液学、血清生化和组织病理学进行评估。在用5 mg/kg和50 mg/kg的AT-533和AT-533凝胶经皮处理的大鼠中未观察到异常变化。然而,在为期15天的急性皮肤毒性研究中,经皮给予250 mg/kg和500 mg/kg的AT-533的大鼠出现食欲和体重下降、不良反应、血液学和生物化学的毒理学相关改变。结论:AT-533的LD50为228.382mg/kg,AT-533凝胶的LD50大于5g/kg。这些发现表明,当剂量小于50mg/kg时,AT-533对大鼠无毒,并且AT-533凝胶在剂量小于5g/kg时可以被认为是无毒的凝胶。
{"title":"Acute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats.","authors":"Lishan Zhong, Yanting Wu, Chen Huang, Kaisheng Liu, Cui-Fang Ye, Zhe Ren, Yifei Wang","doi":"10.1186/s40360-023-00696-5","DOIUrl":"10.1186/s40360-023-00696-5","url":null,"abstract":"<p><strong>Background: </strong>AT-533 is a novel heat shock protein 90 inhibitor that exerting anti-inflammatory, antiviral, and antitumor efficacy. Furthermore, the gel made of AT-533 as raw material named AT-533 gel has the function of repairing keratitis and dermatitis caused by herpes virus infection. However, the acute safety evaluation of AT-533 and AT-533 gel has not been conducted.</p><p><strong>Methods and results: </strong>Herein, we performed acute toxicological studies of AT-533 and AT-533 gel in Sprague-Dawley rats. Fifteen-day acute toxicity study of AT-533 was conducted in both male and female Sprague-Dawley rats at doses of 5, 50, 250 and 500 mg/kg and AT-533 gel at 5 g/kg in the study. During experiment, food consumption and mortality were observed and body weight, hematology, serum biochemistry and histopathological assessment of rats were carried out. No abnormal changes were observed in rats percutaneously treated with AT-533 at 5 mg/kg and 50 mg/kg and AT-533 gel. However, loss of appetite and body weight, adverse reactions, toxicologically relevant alterations in hematology and biochemistry were found in rats percutaneously treated with AT-533 at 250 mg/kg and 500 mg/kg during 15-day acute dermic toxicity study.</p><p><strong>Conclusions: </strong>The aforementioned results suggested that the LD<sub>50</sub> of AT-533 is 228.382 mg/kg and the LD<sub>50</sub> of AT-533 gel is greater than 5 g/kg. These findings indicated that AT-533 is non-toxic in rats when the dose less than 50 mg/kg and AT-533 gel can be considered a gel with no toxicity at doses less than 5 g/kg.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190492","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
Retraction Note: The teratogenic effect of pregabalin on heart, liver and kidney in rats: a light microscopic, electron microscopic and immunohistochemical study. 回缩说明:普瑞巴林对大鼠心脏、肝脏和肾脏的致畸作用:光镜、电镜和免疫组织化学研究。
IF 2.9 3区 医学 Q2 Medicine Pub Date : 2023-10-13 DOI: 10.1186/s40360-023-00697-4
Omnia I Ismail, Eman S Shaltout, Nora Z Abdellah, Diab F Hetta, Wael M A Abd El-Ghani, Lobna A Abdelzaher, Ahmed Mohamed Mohamed Mahmoud, Asmaa M Hasan, Noha A Rashed, Noha Esmael Ebrahem
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引用次数: 0
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BMC Pharmacology & Toxicology
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