Pub Date : 2024-04-04eCollection Date: 2024-04-01DOI: 10.1093/toxres/tfae053
Walaa G Abdelhamid, Sarah A Elmorsy, Ahmed Muhammed, Olfat E Mostafa, Sara Saeed
Background: Poisoning-induced shock is a serious medical emergency with a high mortality rate. Hospitalized poisoned individuals experience multiple adverse cardiovascular events that could progress to cardiac arrest. This study was designed to compare the prognostic role of the admission shock index and plasma copeptin level in shocked poisoned patients and to evaluate their associations with initial patients' characteristics and outcomes.
Methods: We conducted a prospective study on acutely poisoned adult patients.
Results: A total of 41 patients were enrolled in the study. The mean age of all patients was 27.05 ± 10.99 years and most of the patients were females (n = 27, 66%). Pesticides were the most common type of poisoning (n = 18, 44%), followed by cardiovascular drugs (n = 12, 29.3%). Eleven (26.8%) patients died during the hospital stay length. The initial serum copeptin level and shock index could predict organ dysfunction indexed by sequential organ assessment score (SOFA) with area under the curve (AUCs) of 0.862 and 0.755, respectively. Initial serum copeptin and lactate levels, SOFA score, and their combination can strongly differentiate between survivors and non-survivors with an AUC of 0.944, 0.885, and 0.959, and 0.994, respectively.
Conclusion: We concluded that the shock index, serum lactate level, and SOFA score may help in risk stratifying patients and predicting outcomes in critically ill patients with poisoning-induced shock. Copeptin is superior to the shock index in predicting mortality among the studied patients. However, a combination of SOFA score, serum copeptin level, and serum lactate level can develop a more predominant prediction for overall clinical outcomes in these patients.
{"title":"Serum copeptin, lactate, and shock index as predictors of morbidity and mortality in shocked acutely poisoned patients.","authors":"Walaa G Abdelhamid, Sarah A Elmorsy, Ahmed Muhammed, Olfat E Mostafa, Sara Saeed","doi":"10.1093/toxres/tfae053","DOIUrl":"https://doi.org/10.1093/toxres/tfae053","url":null,"abstract":"<p><strong>Background: </strong>Poisoning-induced shock is a serious medical emergency with a high mortality rate. Hospitalized poisoned individuals experience multiple adverse cardiovascular events that could progress to cardiac arrest. This study was designed to compare the prognostic role of the admission shock index and plasma copeptin level in shocked poisoned patients and to evaluate their associations with initial patients' characteristics and outcomes.</p><p><strong>Methods: </strong>We conducted a prospective study on acutely poisoned adult patients.</p><p><strong>Results: </strong>A total of 41 patients were enrolled in the study. The mean age of all patients was 27.05 ± 10.99 years and most of the patients were females (n = 27, 66%). Pesticides were the most common type of poisoning (n = 18, 44%), followed by cardiovascular drugs (n = 12, 29.3%). Eleven (26.8%) patients died during the hospital stay length. The initial serum copeptin level and shock index could predict organ dysfunction indexed by sequential organ assessment score (SOFA) with area under the curve (AUCs) of 0.862 and 0.755, respectively. Initial serum copeptin and lactate levels, SOFA score, and their combination can strongly differentiate between survivors and non-survivors with an AUC of 0.944, 0.885, and 0.959, and 0.994, respectively.</p><p><strong>Conclusion: </strong>We concluded that the shock index, serum lactate level, and SOFA score may help in risk stratifying patients and predicting outcomes in critically ill patients with poisoning-induced shock. Copeptin is superior to the shock index in predicting mortality among the studied patients. However, a combination of SOFA score, serum copeptin level, and serum lactate level can develop a more predominant prediction for overall clinical outcomes in these patients.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Selenium is an important and essential trace element in organisms, but its effects on organisms are also a "double-edged sword". Selenium deficiency or excess can endanger the health of humans and animals. In order to thoroughly understand the nutritional value and toxicity hazards of selenium, researchers have conducted many studies on the model animal zebrafish. However, there is a lack of induction and summary of relevant research on which selenium acts on zebrafish. This paper provides a review of the reported studies. Firstly, this article summarizes the benefits of selenium on zebrafish from three aspects: Promoting growth, Enhancing immune function and anti-tumor ability, Antagonizing some pollutants, such as mercury. Then, three aspects of selenium toxicity to zebrafish are introduced: nervous system and behavior, reproductive system and growth, and damage to some organs. This article also describes how different forms of selenium compounds have different effects on zebrafish health. Finally, prospects for future research directions are presented.
{"title":"The beneficial and toxic effects of selenium on zebrafish. A systematic review of the literature.","authors":"Yuanshan Lin, Liyun Hu, Xinhang Li, Jie Ma, Qipeng Li, Xiaofan Yuan, Yuan Zhang","doi":"10.1093/toxres/tfae062","DOIUrl":"https://doi.org/10.1093/toxres/tfae062","url":null,"abstract":"Selenium is an important and essential trace element in organisms, but its effects on organisms are also a \"double-edged sword\". Selenium deficiency or excess can endanger the health of humans and animals. In order to thoroughly understand the nutritional value and toxicity hazards of selenium, researchers have conducted many studies on the model animal zebrafish. However, there is a lack of induction and summary of relevant research on which selenium acts on zebrafish. This paper provides a review of the reported studies. Firstly, this article summarizes the benefits of selenium on zebrafish from three aspects: Promoting growth, Enhancing immune function and anti-tumor ability, Antagonizing some pollutants, such as mercury. Then, three aspects of selenium toxicity to zebrafish are introduced: nervous system and behavior, reproductive system and growth, and damage to some organs. This article also describes how different forms of selenium compounds have different effects on zebrafish health. Finally, prospects for future research directions are presented.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140768030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nagat F Nawar, D. Beltagy, Tarek M Mohamed, E. Tousson, Mai M. El-Keey
Alzheimer's disease (ad) is a neurological condition that worsens over time and is characterized by the buildup of amyloid (Aβ) plaques in the brain parenchyma. Neuroprotection and cholinesterase inhibition have been the two primary techniques used in the creation of medications to date. In ad, a novel sort of programmed cell death known as ferroptosis takes place along with iron buildup, lipid peroxidation, and glutathione deficiency. The objective of the current investigation was to examine the neuroprotective and anti-ferroptotic role of nanocurcumin and Donepezil against model of aluminum chloride AlCl3 and D-galactose induced ad. The experiment was performed on 70 rats divided into (G1: control, G2: NCMN, G3: Donepezil, G4: ad-model, G5: Donepezil co-treatment, G6: NCMN co-treatment and G7: NCMN+Donepezil co-treatment). Hematological parameters and biochemical investigations as oxidative stress, liver function, kidney function, iron profile and plasma fibrinogen were evaluated. Treatment with Nanocurcumin alone or in combination with Donepezil improved oxidative stress, liver functions, and kidney functions, improve iron profile and decreased plasma fibrinogen.
阿尔茨海默病（AD）是一种随着时间推移而恶化的神经系统疾病，其特征是大脑实质中淀粉样蛋白（Aβ）斑块的堆积。迄今为止，神经保护和胆碱酯酶抑制一直是药物研发的两大主要技术。在广告中，伴随着铁堆积、脂质过氧化和谷胱甘肽缺乏，一种新型的程序性细胞死亡（称为铁突变）也会发生。本次研究的目的是检测纳米姜黄素和多奈哌齐对氯化铝 AlCl3 和 D-半乳糖诱导的 ad 模型的神经保护和抗铁细胞沉降作用。实验对象为 70 只大鼠，分为（G1：对照组；G2：G3：多奈哌齐；G4：广告模型；G5：多奈哌齐联合治疗；G6：多奈哌齐联合治疗；G7：多奈哌齐+多奈哌齐联合治疗）。对血液学参数和氧化应激、肝功能、肾功能、铁概况和血浆纤维蛋白原等生化指标进行了评估。单独使用或与多奈哌齐联合使用纳米姜黄素治疗可改善氧化应激、肝功能和肾功能，改善铁概况并降低血浆纤维蛋白原。
{"title":"Ameliorative anti-coagulant, anti-oxidative and anti-ferroptotic activities of nanocurcumin and donepezil on coagulation, oxidation and ferroptosis in Alzheimer's disease.","authors":"Nagat F Nawar, D. Beltagy, Tarek M Mohamed, E. Tousson, Mai M. El-Keey","doi":"10.1093/toxres/tfae054","DOIUrl":"https://doi.org/10.1093/toxres/tfae054","url":null,"abstract":"Alzheimer's disease (ad) is a neurological condition that worsens over time and is characterized by the buildup of amyloid (Aβ) plaques in the brain parenchyma. Neuroprotection and cholinesterase inhibition have been the two primary techniques used in the creation of medications to date. In ad, a novel sort of programmed cell death known as ferroptosis takes place along with iron buildup, lipid peroxidation, and glutathione deficiency. The objective of the current investigation was to examine the neuroprotective and anti-ferroptotic role of nanocurcumin and Donepezil against model of aluminum chloride AlCl3 and D-galactose induced ad. The experiment was performed on 70 rats divided into (G1: control, G2: NCMN, G3: Donepezil, G4: ad-model, G5: Donepezil co-treatment, G6: NCMN co-treatment and G7: NCMN+Donepezil co-treatment). Hematological parameters and biochemical investigations as oxidative stress, liver function, kidney function, iron profile and plasma fibrinogen were evaluated. Treatment with Nanocurcumin alone or in combination with Donepezil improved oxidative stress, liver functions, and kidney functions, improve iron profile and decreased plasma fibrinogen.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Rossetto, F. Santos, Heloina Nathalliê Mariano da Silva, Elaine Minatel, Mariana Mesquitta, Marcos José Salvador, F. Montico, V. Cagnon
Background Tempol is a redox-cycling nitroxide considered a potent antioxidant. The present study investigated the tempol effects on oxidative stress and mitochondrial markers on prostate cancer (PCa). Methods PC-3 and LnCaP cells were exposed to tempol. Cell viability test, western blot and Amplex Red analyses were performed. In vivo, five experimental groups evaluated tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol doses. Control groups received water as the vehicle. The ventral lobe of the prostate and the blood were collected and submitted to western blotting or enzymatic activity analyses. Results In vitro, tempol decreased cell viability and differentially altered the H2O2 content for PC-3 and LNCaP. Tempol increased SOD2 levels in both cell lines and did not alter Catalase protein levels. In vivo, tempol increased SOD2 levels in the early stage and did not change Catalase levels in the different PCa stages. Systemically, tempol decreased SOD2 levels in the late-stage and improved redox status in the early and late stages, which was confirmed by reduced LDH in tempol groups. Alterations on energetic metabolism and oxidative phosphorylation were observed in TRAMP model. Conclusion Tempol can be considered a beneficial therapy for PCa treatment considering its antioxidant and low toxicity properties, however the PCa progression must be evaluated to get successful therapy.
{"title":"Tempol effect on oxidative and mitochondrial markers in preclinical models for prostate cancer.","authors":"I. Rossetto, F. Santos, Heloina Nathalliê Mariano da Silva, Elaine Minatel, Mariana Mesquitta, Marcos José Salvador, F. Montico, V. Cagnon","doi":"10.1093/toxres/tfae056","DOIUrl":"https://doi.org/10.1093/toxres/tfae056","url":null,"abstract":"Background\u0000Tempol is a redox-cycling nitroxide considered a potent antioxidant. The present study investigated the tempol effects on oxidative stress and mitochondrial markers on prostate cancer (PCa).\u0000\u0000\u0000Methods\u0000PC-3 and LnCaP cells were exposed to tempol. Cell viability test, western blot and Amplex Red analyses were performed. In vivo, five experimental groups evaluated tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol doses. Control groups received water as the vehicle. The ventral lobe of the prostate and the blood were collected and submitted to western blotting or enzymatic activity analyses.\u0000\u0000\u0000Results\u0000In vitro, tempol decreased cell viability and differentially altered the H2O2 content for PC-3 and LNCaP. Tempol increased SOD2 levels in both cell lines and did not alter Catalase protein levels. In vivo, tempol increased SOD2 levels in the early stage and did not change Catalase levels in the different PCa stages. Systemically, tempol decreased SOD2 levels in the late-stage and improved redox status in the early and late stages, which was confirmed by reduced LDH in tempol groups. Alterations on energetic metabolism and oxidative phosphorylation were observed in TRAMP model.\u0000\u0000\u0000Conclusion\u0000Tempol can be considered a beneficial therapy for PCa treatment considering its antioxidant and low toxicity properties, however the PCa progression must be evaluated to get successful therapy.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Varsha Singh, Payal Mandal, S. Chauhan, Ishrat Jahan Saifi, Marhaba, P. V. Sandeep, P. Jagdale, Anjaneya Ayanur, K. Ansari
Background Zearalenone (ZEA), a natural food contaminant, is reported to act as a mycoestrogen due to its estrogen-mimicking properties. According to studies, ZEA has a greater potential for estrogenic activity compared to any other naturally occurring non-steroidal estrogen. ZEA has been found in the endometrium of individuals with reproductive problems and the serum of children facing early puberty. These studies suggested a possible link between ZEA exposure and endometrial toxicity; nonetheless, no thorough research has been done. This study assessed the endometrium's response to chronic ZEA exposure. Methods Four groups of CD-1 female mice were exposed to control, estradiol (E2), and two different doses of ZEA for 90 days. At the end of treatment, blood and uterus were collected, and samples were used for inflammatory cytokines level, immunochemical, histopathological, and biophysical analysis. Results Our data indicated that the uterus showed a change in body/organ weight ratio, while other organs did not have any notable changes. Immunochemical and histological studies showed hyperplasia and a higher number of glands in the endometrium after ZEA and E2 exposure. Similarly, proliferation markers such as proliferative cell nuclear antigen (PCNA), Ki-67, and inflammatory cytokines such as interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon-gamma (IFN-?) levels were found to be higher in the E2 and ZEA-exposed groups. Conclusion Our finding conclude that ZEA targets the uterus and cause inflammation due to increased levels of inflammatory cytokines and proliferation mediators, as well as systemic toxicity denoted by a strong binding affinity with serum proteins.
{"title":"Chronic exposure to Zearalenone leads to endometrial hyperplasia in CD-1 mice by altering the inflammatory markers.","authors":"Varsha Singh, Payal Mandal, S. Chauhan, Ishrat Jahan Saifi, Marhaba, P. V. Sandeep, P. Jagdale, Anjaneya Ayanur, K. Ansari","doi":"10.1093/toxres/tfae055","DOIUrl":"https://doi.org/10.1093/toxres/tfae055","url":null,"abstract":"Background\u0000Zearalenone (ZEA), a natural food contaminant, is reported to act as a mycoestrogen due to its estrogen-mimicking properties. According to studies, ZEA has a greater potential for estrogenic activity compared to any other naturally occurring non-steroidal estrogen. ZEA has been found in the endometrium of individuals with reproductive problems and the serum of children facing early puberty. These studies suggested a possible link between ZEA exposure and endometrial toxicity; nonetheless, no thorough research has been done. This study assessed the endometrium's response to chronic ZEA exposure.\u0000\u0000\u0000Methods\u0000Four groups of CD-1 female mice were exposed to control, estradiol (E2), and two different doses of ZEA for 90 days. At the end of treatment, blood and uterus were collected, and samples were used for inflammatory cytokines level, immunochemical, histopathological, and biophysical analysis.\u0000\u0000\u0000Results\u0000Our data indicated that the uterus showed a change in body/organ weight ratio, while other organs did not have any notable changes. Immunochemical and histological studies showed hyperplasia and a higher number of glands in the endometrium after ZEA and E2 exposure. Similarly, proliferation markers such as proliferative cell nuclear antigen (PCNA), Ki-67, and inflammatory cytokines such as interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon-gamma (IFN-?) levels were found to be higher in the E2 and ZEA-exposed groups.\u0000\u0000\u0000Conclusion\u0000Our finding conclude that ZEA targets the uterus and cause inflammation due to increased levels of inflammatory cytokines and proliferation mediators, as well as systemic toxicity denoted by a strong binding affinity with serum proteins.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140792536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meray Medhat Shokry Zaghary, Mai M Abd ElKader, Rasha Elhaddad Ali Mousa, Ahmed M Said
Background Toxicologists manage poisoning by preventing, detecting, and treating it, which requires continuous data collection and analysis of toxicological hazards. Aim of the work The study aims to report and compare the pattern and outcome of acute toxicological cases admitted to Sohag University Hospitals during the COVID-19 lockdown (2020-2021) with the year before (2019) and the year after (2022). Methods This comparative study reviewed the sociodemographic and clinical data in the medical records. The study showed that Sohag University Hospitals received 670 toxicological cases between 2019 and 2022; 105 cases in 2019, 347 cases in 2020-2021, and 218 cases in 2022. Results Most of patients were below seven years with no sex differences. Accidental poisoning was the most frequent toxicity. The oral route was the most common in the three studied periods. During the lockdown, metal phosphide was the most frequent (19.0%), while therapeutic agents were the most reported after the lockdown (23.9%). The delay time showed a significant difference between the studied periods (p-value < 0.001). In the three studied periods, complete recovery was achieved in more than 70% of cases; however, the mortality rate and the rate of complications during the lockdown period (10.4% and 9.5%, respectively) were almost twice those of the year before and the year after the pandemic with significant odds ratio of mortality during pandemic (OR) 0.07 CI 95% (0.02, 0.11). Conclusion The pandemic had a bad impact on outcomes as showed the highest percentage of mortality compared to before and after COVID-19 periods.
{"title":"Patterns and outcomes of acute toxicological cases before, during, and after COVID-19 lockdown in Sohag University hospitals, Egypt.","authors":"Meray Medhat Shokry Zaghary, Mai M Abd ElKader, Rasha Elhaddad Ali Mousa, Ahmed M Said","doi":"10.1093/toxres/tfae061","DOIUrl":"https://doi.org/10.1093/toxres/tfae061","url":null,"abstract":"Background\u0000Toxicologists manage poisoning by preventing, detecting, and treating it, which requires continuous data collection and analysis of toxicological hazards.\u0000\u0000\u0000Aim of the work\u0000The study aims to report and compare the pattern and outcome of acute toxicological cases admitted to Sohag University Hospitals during the COVID-19 lockdown (2020-2021) with the year before (2019) and the year after (2022).\u0000\u0000\u0000Methods\u0000This comparative study reviewed the sociodemographic and clinical data in the medical records. The study showed that Sohag University Hospitals received 670 toxicological cases between 2019 and 2022; 105 cases in 2019, 347 cases in 2020-2021, and 218 cases in 2022.\u0000\u0000\u0000Results\u0000Most of patients were below seven years with no sex differences. Accidental poisoning was the most frequent toxicity. The oral route was the most common in the three studied periods. During the lockdown, metal phosphide was the most frequent (19.0%), while therapeutic agents were the most reported after the lockdown (23.9%). The delay time showed a significant difference between the studied periods (p-value < 0.001). In the three studied periods, complete recovery was achieved in more than 70% of cases; however, the mortality rate and the rate of complications during the lockdown period (10.4% and 9.5%, respectively) were almost twice those of the year before and the year after the pandemic with significant odds ratio of mortality during pandemic (OR) 0.07 CI 95% (0.02, 0.11).\u0000\u0000\u0000Conclusion\u0000The pandemic had a bad impact on outcomes as showed the highest percentage of mortality compared to before and after COVID-19 periods.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140774733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongliang Xie, Aolin Zhang, Junwei Li, Xuanting Mou, Tao He, Tsz Ching Yeung, Clara Bik-San Lau, Zhong Zuo, Ping Li, E. J. Kennelly, Ping Chung Leung, Yu Tang, Xiaohui Fan, C. Wang, Lu Li
Objective The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR. Methods The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms. Conclusions Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.
目的白术（菊科植物）的根茎被称为白术根茎，传统名称为白术。(白术（Atractylodes macrocephala Koidz）（菊科），又名白术根茎，传统名称为白术，是一种常用的预防流产的中药材。然而，我们之前的研究发现，在怀孕期间服用大剂量的白术根茎可导致胚胎毒性，但具体的胚胎毒性成分及其内在机制仍不清楚。本研究旨在筛选和鉴定AMR中潜在的胚胎毒性成分。方法采用薄层色谱法分析AMR提取物和子馏分，然后通过体外小鼠肢芽显微质谱和小鼠全胚培养生物测定进行筛选。利用怀孕小鼠模型对 AMR 的胚胎毒性馏分进行了进一步的体内评估。利用基质辅助激光解吸/电离串联飞行时间质谱（MALDI-TOF/TOF-MS）分析了潜在胚胎毒性成分的结构。结果体外和体内生物测定显示，AMR 富含苷类的亚馏分（AMR-A-IIa 和 AMR-A-IIb）具有潜在的胚胎毒性。妊娠动物服用这些亚馏分后，会增加死胎和先天性肢体畸形的发生率。质谱分析确定了这两种亚馏分中的环黄酮衍生物，表明它们可能在观察到的肢体畸形中起了作用。结论我们的研究为 AMR 的药理毒性提供了重要的科学依据，这对于妊娠期常用中药的安全临床应用非常重要。
{"title":"Cycasin derivative: a potential embryotoxic component of Atractylodes macrocephala rhizome for limb malformation.","authors":"Hongliang Xie, Aolin Zhang, Junwei Li, Xuanting Mou, Tao He, Tsz Ching Yeung, Clara Bik-San Lau, Zhong Zuo, Ping Li, E. J. Kennelly, Ping Chung Leung, Yu Tang, Xiaohui Fan, C. Wang, Lu Li","doi":"10.1093/toxres/tfae057","DOIUrl":"https://doi.org/10.1093/toxres/tfae057","url":null,"abstract":"Objective\u0000The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR.\u0000\u0000\u0000Methods\u0000The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS).\u0000\u0000\u0000Results\u0000In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms.\u0000\u0000\u0000Conclusions\u0000Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140789640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-31eCollection Date: 2024-04-01DOI: 10.1093/toxres/tfae052
Rou-Jun Wang, Guang-Chao Ma, Shun Yu, Mei Zhang, Shi-Biao Pu
Objective: Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy.
Methods: We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA).
Results: Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels.
Conclusions: This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.
目的：中风是导致全球数百万人死亡和残疾的主要原因，其中 80% 为缺血性中风（IS）。近来，传统中药因其毒副作用小、安全性高而在治疗缺血性中风方面受到广泛关注。步阳黄芩汤（BHD）是一味经典名方，用于治疗中风致残已有数百年历史。然而，它的内在机制仍是一个谜：方法：我们首先通过大脑中动脉闭塞（MCAO）建立了一个 IS 模型。方法：我们首先通过大脑中动脉闭塞（MCAO）构建了一个 IS 模型，然后使用 UHPLC-QTOF/MS 对血清样本进行了代谢组学研究，随后进行了多变量数据分析，包括主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）：结果：PCA的代谢谱分析表明，BHD能将MCAO引起的代谢紊乱调节到正常水平，这与神经行为学评估结果一致。在 OPLS-DA 中，有 12 种代谢物被筛选为参与 MCAO 诱导的 IS 的潜在生物标记物。三个代谢途径被认为是最相关的途径，分别涉及叶酸的一个碳库、鞘脂代谢和磷酸肌醇代谢。BHD能明显逆转7种代谢物的异常，使其恢复到正常水平：这是首次从代谢物水平研究 BHD 对 IS 的影响，并揭示 BHD 的内在机制，这与神经行为评估是相辅相成的。从广义上讲，本研究为评价中药的疗效、解释中药的作用机制提供了新颖而有价值的见解，为临床实践中进一步研究中药的治疗机制提供了理论依据。
{"title":"UPLC-MS based metabonomics revealed the protective effects of Buyang Huanwu decoction on ischemic stroke rats.","authors":"Rou-Jun Wang, Guang-Chao Ma, Shun Yu, Mei Zhang, Shi-Biao Pu","doi":"10.1093/toxres/tfae052","DOIUrl":"https://doi.org/10.1093/toxres/tfae052","url":null,"abstract":"<p><strong>Objective: </strong>Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy.</p><p><strong>Methods: </strong>We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA).</p><p><strong>Results: </strong>Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels.</p><p><strong>Conclusions: </strong>This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28eCollection Date: 2024-04-01DOI: 10.1093/toxres/tfae050
Aliaa M Radwan, Doaa T Gebreel, Sahar Allam, Afaf El-Atrash, Ehab Tousson
Background: Ehrlich ascites carcinoma (EAC) is a rapidly growing and undifferentiated tumor that can prompt oxidative stress and liver toxicity, whereas chitosan and Grifola Frondosa have widely recognized biological qualities. Therefore, our study designed to assess the potential ameliorative ability of chitosan nanoparticles (CS NPs) and Grifola Frondosa nanoparticles (GF-loaded casein NPs) on EAC-induced hepatic injury in mice.
Methods: A total of 60 female albino mice were segregated into 6 groups (10 mice each), G1, control group; G2, CS NPs group; G3, GF-loaded casein NPs group; G4, EAC group; G5, EAC treated with CS NPs; G6, EAC treated with GF-loaded casein NPs.
Results: According to the findings, EAC considerably increased serum activities of ALT, AST, ALP as well as LDL, cholesterol, and triglycerides levels coincided with marked decrease in albumin and total protein content in liver tissue. At the same time, it drastically lowered GSH levels and catalase activity while significantly elevating MDA levels. In addition, EAC caused DNA damage and apoptosis by decreasing Bcl-2 while increasing p53 expressions. However, either CS NPs or GF-loaded casein NPs therapy improved liver architecture and functioning, increased antioxidant parameters, and prevented hepatocyte death in EAC mice.
Conclusions: Our findings concluded that CS NPs and GF-loaded casein NPs have insulating functions against EAC-induced hepatic damage in mice.
{"title":"Chitosan and <i>Grifola Frondosa</i> nanoparticles insulate liver dysfunction in EAC-bearing mice.","authors":"Aliaa M Radwan, Doaa T Gebreel, Sahar Allam, Afaf El-Atrash, Ehab Tousson","doi":"10.1093/toxres/tfae050","DOIUrl":"10.1093/toxres/tfae050","url":null,"abstract":"<p><strong>Background: </strong>Ehrlich ascites carcinoma (EAC) is a rapidly growing and undifferentiated tumor that can prompt oxidative stress and liver toxicity, whereas chitosan and <i>Grifola Frondosa</i> have widely recognized biological qualities. Therefore, our study designed to assess the potential ameliorative ability of chitosan nanoparticles (CS NPs) and Grifola Frondosa nanoparticles (GF-loaded casein NPs) on EAC-induced hepatic injury in mice.</p><p><strong>Methods: </strong>A total of 60 female albino mice were segregated into 6 groups (10 mice each), G1, control group; G2, CS NPs group; G3, GF-loaded casein NPs group; G4, EAC group; G5, EAC treated with CS NPs; G6, EAC treated with GF-loaded casein NPs.</p><p><strong>Results: </strong>According to the findings, EAC considerably increased serum activities of ALT, AST, ALP as well as LDL, cholesterol, and triglycerides levels coincided with marked decrease in albumin and total protein content in liver tissue. At the same time, it drastically lowered GSH levels and catalase activity while significantly elevating MDA levels. In addition, EAC caused DNA damage and apoptosis by decreasing Bcl-2 while increasing p53 expressions. However, either CS NPs or GF-loaded casein NPs therapy improved liver architecture and functioning, increased antioxidant parameters, and prevented hepatocyte death in EAC mice.</p><p><strong>Conclusions: </strong>Our findings concluded that CS NPs and GF-loaded casein NPs have insulating functions against EAC-induced hepatic damage in mice.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28eCollection Date: 2024-04-01DOI: 10.1093/toxres/tfae034
Walaa A Moselhy, Marwa A Ibrahim, Ahlam G Khalifa, El-Shaymaa El-Nahass, Nour El-Houda Y Hassan
Introduction: Metal oxide nanoparticles are currently used widely in many aspects of human and animal life with broad prospects for biomedical purposes. The present work was carried out to investigate the effects of orally administrated TiO2NPs, ZnONPs, IONs and Al2O3NPs on the mRNA expression level of CYP 1A1 and NBN in the rat liver.
Materials and methods: Four groups of male Albino rats were given their respective treatment orally for 60 days in a dose of 1/20 of the LD50 TiO2NPs (600 mg/Kg b.wt/day), ZnONPs (340 mg/Kg b.wt/day), IONs (200 mg/kg b.wt/day) and Al2O3NPs (100 mg/Kg b.wt/day) and a fifth group served as a control group.
Rresults: The mRNA level of CYP 1A1 and NBN showed up-regulation in all the NPs-treated groups relative to the control group. ZnONPs group recorded the highest expression level while the TiO2NPs group showed the lowest expression level transcript. Conclusion:The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide, iron oxide nanoparticles and titanium dioxide, respectively.
{"title":"The effects of TiO2, ZnO, IONs and Al2O3 metallic nanoparticles on the <i>CYP1A1</i> and <i>NBN</i> transcripts in rat liver.","authors":"Walaa A Moselhy, Marwa A Ibrahim, Ahlam G Khalifa, El-Shaymaa El-Nahass, Nour El-Houda Y Hassan","doi":"10.1093/toxres/tfae034","DOIUrl":"10.1093/toxres/tfae034","url":null,"abstract":"<p><strong>Introduction: </strong>Metal oxide nanoparticles are currently used widely in many aspects of human and animal life with broad prospects for biomedical purposes. The present work was carried out to investigate the effects of orally administrated TiO2NPs, ZnONPs, IONs and Al<sub>2</sub>O<sub>3</sub>NPs on the mRNA expression level of CYP 1A1 and <i>NBN</i> in the rat liver.</p><p><strong>Materials and methods: </strong>Four groups of male Albino rats were given their respective treatment orally for 60 days in a dose of 1/20 of the LD50 TiO2NPs (600 mg/Kg b.wt/day), ZnONPs (340 mg/Kg b.wt/day), IONs (200 mg/kg b.wt/day) and Al<sub>2</sub>O<sub>3</sub>NPs (100 mg/Kg b.wt/day) and a fifth group served as a control group.</p><p><strong>Rresults: </strong>The mRNA level of CYP 1A1 and <i>NBN</i> showed up-regulation in all the NPs-treated groups relative to the control group. ZnONPs group recorded the highest expression level while the TiO2NPs group showed the lowest expression level transcript. Conclusion:The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide, iron oxide nanoparticles and titanium dioxide, respectively.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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