Drug and Chemical Toxicology最新文献_第5页

Curcumin and quercetin can ameliorate arsenic and smokeless tobacco induced reproductive toxicity in female mice. 姜黄素和槲皮素可改善砷和无烟烟草引起的雌性小鼠生殖毒性。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-08-18 DOI: 10.1080/01480545.2025.2547660

Sweety Nath Barbhuiya, Dharmeswar Barhoi, Pubali Dey, Anirudha Giri, Sarbani Giri

{"title":"Curcumin and quercetin can ameliorate arsenic and smokeless tobacco induced reproductive toxicity in female mice.","authors":"Sweety Nath Barbhuiya, Dharmeswar Barhoi, Pubali Dey, Anirudha Giri, Sarbani Giri","doi":"10.1080/01480545.2025.2547660","DOIUrl":"10.1080/01480545.2025.2547660","url":null,"abstract":"Arsenic contamination of ground water is a global problem. Consumption of smokeless tobacco called 'sadagura' is a common lifestyle practice in Assam, India. As a result, the population is more vulnerable to health outcomes with regard to female reproductive anomalies. Phytochemicals are abundant in antioxidants, the current study examined the protective effects of quercetin (Qc) and curcumin (Cur) against the toxicity caused by smokeless tobacco and arsenic. Female Swiss albino mice (N = 66) were randomly divided into eleven different groups viz., Control, Positive control (DMSO), Sodium arsenite (SA), Sadagura(SG), SA+SG, SA+Qc, SG+Qc, SA+SG+Qc, SA+Cur, SG+Cur, and SA+SG+Cur. Estrous cycle; ovarian and uterine histopathological changes were recorded. Utilizing the comet assay, the DNA damage of tissues was examined, and biochemical analysis was performed to determine oxidative stress level. The study of estrous cycle showed that changes in different phases of estrous cycle was altered by both As and SG exposure. However, Qc and Cur exposure showed a significant notable recovery. It was observed that Qc and Cur lowered the DNA damage induced by As and SG. Histological examinations showed abnormal tissue architecture in mice treated with SG and SA that is restored by administration of curcumin and quercetin. In contrast to As and SG treatment, quercetin and curcumin supplementation significantly increased GSH and SOD activity in experimental mice. According to the current study, curcumin and quercetin lowered the induced oxidative stress. Therefore, these phytochemicals can act as a protective mediator against the female reproductive toxicity caused by smokeless tobacco and arsenic coexposure.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-15"},"PeriodicalIF":1.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871971","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}

引用次数: 0

Synergistic effect of piperine on curcumin in cisplatin-induced nephrotoxicity through DNA fragmentation and cytokines gene expressions. 胡椒碱通过DNA片段化和细胞因子基因表达对姜黄素在顺铂所致肾毒性中的协同作用。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-08-11 DOI: 10.1080/01480545.2025.2543421

Sohail Hussain, Mohammad Ashafaq, Saeed Alshahrani, Marwa Qadri, Amani Khardali, Wedad Mawkili, Dalin A Hassan, Mohammad Intakhab Alam, Yosif Almoshari, Manal Mohammed Elhassan Taha, Rahimullah Siddiqui

{"title":"Synergistic effect of piperine on curcumin in cisplatin-induced nephrotoxicity through DNA fragmentation and cytokines gene expressions.","authors":"Sohail Hussain, Mohammad Ashafaq, Saeed Alshahrani, Marwa Qadri, Amani Khardali, Wedad Mawkili, Dalin A Hassan, Mohammad Intakhab Alam, Yosif Almoshari, Manal Mohammed Elhassan Taha, Rahimullah Siddiqui","doi":"10.1080/01480545.2025.2543421","DOIUrl":"https://doi.org/10.1080/01480545.2025.2543421","url":null,"abstract":"Cisplatin (Cis) is an anticancer drug commonly used to treat solid tumors. However, because of its nephrotoxicity, its use is limited. Our goal was to evaluate the effects of curcumin (Cur) and piperine (Pip) administered separately versus combined on Cis-induced nephrotoxicity in rats. Significant adverse physiological, biochemical, and histological effects, such as decreased body weight, renal damage indices in serum and kidney tissue of indicated nephrotoxicity are caused by Cis (6 mg/kg, intraperitoneally i.p.). Cis also altered histological changes, DNA damage, renal oxidative stress, and several pro-inflammatory cytokines. By reducing proinflammatory and apoptotic mediators and enhancing antioxidant competence in the renal tissues of Cis-treated rats by supplementation with either Cur (200 mg/kg o.p.) or Pip (20 mg/kg o.p.) administered singly for 12 days, notably reduced the negative renal effects of Cis. In all the parameters, the ameliorative effect was greatly increased when Cur and Pip were administered together.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":1.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820904","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}

引用次数: 0

Co-administered chitosan and ivy leaf extract reduce deltamethrin-induced testicular toxicity. 壳聚糖和常青藤叶提取物共同施用可降低溴氰菊酯引起的睾丸毒性。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-08-08 DOI: 10.1080/01480545.2025.2543420

Asmaa Mohammad Moawad, Fatma Shaban, Abla Abdelmeguid Attia, Marwa Abdelgwad, Sara Adel Hosny, Basma Kamal Ibrahim

{"title":"Co-administered chitosan and ivy leaf extract reduce deltamethrin-induced testicular toxicity.","authors":"Asmaa Mohammad Moawad, Fatma Shaban, Abla Abdelmeguid Attia, Marwa Abdelgwad, Sara Adel Hosny, Basma Kamal Ibrahim","doi":"10.1080/01480545.2025.2543420","DOIUrl":"https://doi.org/10.1080/01480545.2025.2543420","url":null,"abstract":"Deltamethrin, a synthetic pesticide, is toxic to both mammalian and nonmammalian animal species. Despite its widespread use in agriculture, food safety, and disease vector control, it poses a threat to a variety of organisms. The current study was designed to investigate the potential protective effects of chitosan, ivy leaf extract, or both on testicular toxicity when coadministered with the pesticide deltamethrin. Forty-eight rats were divided into eight groups of six each. All the animals were subjected to intragastric incubation for 90 days and received either saline (the control) or one of the following substances: the polysaccharide chitosan, ivy leaf extract, a combination of these two substances, deltamethrin alone, or a combination of deltamethrin with chitosan and ivy leaf extract. After the rats were euthanized, blood was drawn for biochemical assessment, and the testes were dissected for histological and immunohistochemical assessment. This study revealed that deltamethrin toxicity in rats resulted in reduced body weight, decreased sex hormones, increased oxidative activity, and decreased antioxidant defenses. Histopathological analysis revealed abnormal seminiferous tubules and damaged spermatogenic cells. The coadministration of chitosan and ivy leaf extract with deltamethrin reversed these effects by increasing body weight, reducing oxidative stress, and preventing histologic damage.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":1.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798491","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}

引用次数: 0

Identification of the chemical constituents of Juglans regia ethanol extract by L-MS/MS and its effects on 5-FU-induced autophagy, oxidative stress, and apoptosis. L-MS/MS法鉴定核桃乙醇提取物的化学成分及其对5- fu诱导的自噬、氧化应激和细胞凋亡的影响。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-08-08 DOI: 10.1080/01480545.2025.2543419

Hamit Uslu, Gözde Atila Uslu, Taha Abdulkadir Çoban, Mustafa Özkaraca, Ali Sefa Mendil, Hasan Can

{"title":"Identification of the chemical constituents of Juglans regia ethanol extract by L-MS/MS and its effects on 5-FU-induced autophagy, oxidative stress, and apoptosis.","authors":"Hamit Uslu, Gözde Atila Uslu, Taha Abdulkadir Çoban, Mustafa Özkaraca, Ali Sefa Mendil, Hasan Can","doi":"10.1080/01480545.2025.2543419","DOIUrl":"https://doi.org/10.1080/01480545.2025.2543419","url":null,"abstract":"5-fluorouracil (5-FU) is an important chemotherapeutic agent that has been used alone or in combination with other chemotherapeutics for years in the treatment of various malignancies. However, as with other chemotherapeutic agents, the disadvantage of 5-FU is that it damages healthy cells as well as cancer cells. Natural compounds are the first option that comes to mind to reduce and/or prevent undesirable side effects of chemotherapeutics. In this study, we aimed to determine the effects of Juglans regia extract (JR), whose antioxidant, anti-inflammatory, anti-diabetic, and antimicrobial effects were previously determined, on 5-FU-induced autophagy, oxidative stress, and apoptosis after its constituents were determined by LC-MS/MS. Experimental groups were formed as Control (C), JR, 5-FU, and JR + 5-FU. Rats were pretreated with JR at a dose of 200 mg/kg for seven days, and on the eighth day, a single dose of 100 mg/kg 5-FU was administered intraperitoneally to the JR + 5-FU and 5-FU groups. 5-FU disturbed the oxidant-antioxidant balance by increasing Keap1, TOS, and 8-OHdG levels and decreasing TAS levels and triggered cellular autophagy and apoptosis by increasing LC3B, Bax, and Caspase-3 levels and decreasing Bcl-2. JR pretreatment was shown to have modulating effects on the Keap1/Nrf2 pathway in the reorganization of the oxidant-antioxidant balance, to show anti-apoptotic activity, and to partially alleviate autophagy. JR's bioactive components were shown to alleviate oxidative stress and associated DNA damage via Keap1/Nrf2 and also attenuate fluorouracil-induced kidney damage by reducing autophagy and apoptosis, two important forms of programmed cell death, and have a promising potential against nephrotoxicity.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":1.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798492","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}

引用次数: 0

Phenolic profile, in vitro antioxidant and safety evaluation of extract obtained from Citrus maxima Burm. Merr. seeds. 柑橘提取物的酚类特征、体外抗氧化性及安全性评价。稳定。种子。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-08-07 DOI: 10.1080/01480545.2025.2541653

Arnab Sarkar, Akash De, Tanmoy Banerjee, Avishek Mandal, Rudranil Bhowmik, Md Adil Shaharyar, Nilanjan Ghosh, Sanmoy Karmakar

{"title":"Phenolic profile, in vitro antioxidant and safety evaluation of extract obtained from Citrus maxima Burm. Merr. seeds.","authors":"Arnab Sarkar, Akash De, Tanmoy Banerjee, Avishek Mandal, Rudranil Bhowmik, Md Adil Shaharyar, Nilanjan Ghosh, Sanmoy Karmakar","doi":"10.1080/01480545.2025.2541653","DOIUrl":"https://doi.org/10.1080/01480545.2025.2541653","url":null,"abstract":"Citrus maxima (Burm). Merr. (CM) has been extensively documented worldwide for its diversified ethno-pharmacological activities. Although the seeds have been previously evaluated for their anxiolytic, analgesic and anti-inflammatory properties, they have not been extensively studied, unlike other plant parts. This study investigates the phytochemical composition and oral toxicity profile of ethanolic seed extract of CM (EESCM) in male and female balb/c mice. TPC and HPLC analyses confirmed the presence of phytoconstituents like naringin, caffeic acid, and hesperidin. Acute toxicity testing involved oral administration of EESCM at 1000, 2000, and 3000 mg/kg body weight (B.W.) over 14 days, revealing no observable toxicity signs. In the subacute study, mice received doses of 300, 600, and 900 mg/kg for 28 days. No significant alterations were observed in food and water intake or most hematological and biochemical parameters, except AST elevation in both sexes. There were no major histological manifestations of tissue damage in 300 and 600 mg/kg, but some changes were detected in the liver, kidney, and spleen at 900 mg/kg. The findings suggested that EESCM is reasonably nontoxic in mice. This effect could be due to the presence of potent antioxidants, which could be beneficial for providing therapeutic activities for the seeds in the future.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-18"},"PeriodicalIF":1.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798493","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}

引用次数: 0

A comprehensive review of artesunate-induced organ toxicity: mechanisms, resistance, biomarkers, and protective strategies. 青蒿琥酯诱导的器官毒性：机制、耐药性、生物标志物和保护策略的综合综述。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-08-07 DOI: 10.1080/01480545.2025.2543422

Sudip Prasad Jena, Sabina Evan Prince

{"title":"A comprehensive review of artesunate-induced organ toxicity: mechanisms, resistance, biomarkers, and protective strategies.","authors":"Sudip Prasad Jena, Sabina Evan Prince","doi":"10.1080/01480545.2025.2543422","DOIUrl":"https://doi.org/10.1080/01480545.2025.2543422","url":null,"abstract":"This paper provides a comprehensive analysis of artesunate (ART), highlighting its dual role as a highly effective antimalarial agent and its potential to induce organ toxicity under certain conditions, particularly with prolonged use over an extended period. This review highlights the favorable pharmacological properties of ART and its derivatives, while also addressing growing concerns over their associated adverse effects. It provides an in-depth exploration of the underlying mechanisms of ART-induced toxicity and discusses potential protective strategies and mitigation approaches aimed at minimizing these toxicities. This systematic review compiles recent studies on ART-induced organ toxicity, with a particular focus on key underlying mechanisms, including oxidative stress, inflammation, and apoptotic signaling pathways. It also explores the various diagnostic methods used to assess toxicity, providing insight into how organ damage related to ART is identified and evaluated. Overall, this paper underscores the need for more comprehensive research, including well-designed clinical trials, to better understand and manage the potential toxic effects of ART. Strengthening this knowledge is essential to ensure that the risk of organ damage does not compromise the life-saving benefits of malaria treatment.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":1.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793715","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}

引用次数: 0

Evidence of non-carcinogenicity of rhubarb extract: a 2-year feeding study in SD rats. 大黄提取物无致癌性的证据：SD大鼠2年喂养研究。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-29 DOI: 10.1080/01480545.2025.2536525

Liwen Zhou, Ji Liu, Wenxiang Yang, Yanhua Zheng, Jingjing Qu, Xiaoqiao Tang, Hong Bai, Chunxia Liu, Bolin Fan

{"title":"Evidence of non-carcinogenicity of rhubarb extract: a 2-year feeding study in SD rats.","authors":"Liwen Zhou, Ji Liu, Wenxiang Yang, Yanhua Zheng, Jingjing Qu, Xiaoqiao Tang, Hong Bai, Chunxia Liu, Bolin Fan","doi":"10.1080/01480545.2025.2536525","DOIUrl":"https://doi.org/10.1080/01480545.2025.2536525","url":null,"abstract":"This study evaluated the carcinogenicity and determined the no observed adverse effect level (NOAEL) of rhubarb extract in Sprague-Dawley (SD) rats over two years.SD rats (104 per group, equal males/females) were randomly assigned to a control (0 mg/kg BW) and three treatment groups (101, 405, and 1620 mg/kg BW). The extract was administered via diet for 104 weeks. Body weight, food consumption, urinalysis, hematology, organ-to-body weight ratios, and histopathology were analyzed. The 1620 mg/kg group showed significantly lower weight gain. Urinalysis revealed elevated ketones, nitrites, and reduced pH in1620 mg/kg BW group. Alkaline phosphatase (ALP) increased in 1620 mg/kg BW dose group of females, and blood glucose rose in 1620 mg/kg BW dose group of males. Activated partial thromboplastin time (APTT) was prolonged at 405 and 1620 mg/kg. Significant tubular pigment deposition was observed in kidneys at 405 and 1620 mg/kg, but no significant differences in tumor incidence were noted. The no observed adverse effect level (NOAEL) for rhubarb extract was 101 mg/kg BW, while the lowest observed adverse effect level (LOAEL) was 405 mg/kg BW. The liver and kidneys were primary toxicity targets. Rhubarb extract exhibited no carcinogenic potential in SD rats.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":1.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728744","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}

引用次数: 0

Evaluation of toxicological profile of omeprazole degradation impurities in an intravenous drug product: omeprazole-sulfone and omeprazole-N-oxide. 静脉注射药品奥美拉唑-砜和奥美拉唑- n -氧化物中奥美拉唑降解杂质的毒理学评价。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-28 DOI: 10.1080/01480545.2025.2537262

Engin Sumer, Muhammed Hamitoğlu, Gulcin Tugcu, Gülşah Esen, Ayşe Gökçen Kılıç, Alev Cumbul, Sinem Helvacıoğlu Akyüz, Ahmet Aydın

{"title":"Evaluation of toxicological profile of omeprazole degradation impurities in an intravenous drug product: omeprazole-sulfone and omeprazole-N-oxide.","authors":"Engin Sumer, Muhammed Hamitoğlu, Gulcin Tugcu, Gülşah Esen, Ayşe Gökçen Kılıç, Alev Cumbul, Sinem Helvacıoğlu Akyüz, Ahmet Aydın","doi":"10.1080/01480545.2025.2537262","DOIUrl":"https://doi.org/10.1080/01480545.2025.2537262","url":null,"abstract":"Omeprazole (OMZ) is a widely used proton pump inhibitor for the treatment of acid-related gastrointestinal disorders. Degradation during the manufacture and storage of the drug substance or drug product may lead to the formation of impurities. When these impurities exceed the qualification threshold defined by ICH Q3B(R2), toxicological evaluation becomes essential. This study aimed to assess the genotoxic and systemic toxicity potential of OMZ-sulfone (impurity D) and OMZ-N-oxide (impurity E), which are OMZ degradation impurities and are formed during the manufacturing and storage of the drug product using an integrated in silico, in vitro, and in vivo approach. Alternative qualification strategies, such as the use of metabolism data and compendial limits, were considered but found insufficient to confirm the safety of the impurities. In silico predictions using multiple QSAR platforms classified OMZ-sulfone as non-mutagenic (class 4 impurity), while OMZ-N-oxide exhibited structural alerts not found in the parent compound, necessitating further testing as a class 3 impurity. Ames test results confirmed that OMZ-N-oxide was non-mutagenic in five S. typhimurium strains up to 1000 µg/plate. A 14-day repeated-dose toxicity study in rats receiving an OMZ product containing both impurities showed no mortality, clinical signs, or adverse effects on hematological, biochemical, or histopathological parameters. These findings indicate that OMZ-N-oxide does not pose a genotoxic or systemic toxicity risk under the tested conditions. OMZ-sulfone was also predicted to be non-mutagenic. Overall, both impurities may be considered safe when present above the qualification threshold, supporting their continued monitoring and control in OMZ-containing pharmaceutical products.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728743","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}

引用次数: 0

Pubertal atrazine exposure promotes adipocyte hypertrophy and hepatic steatosis in adult mice on a high-fat diet. 青春期接触阿特拉津会促进高脂肪饮食的成年小鼠的脂肪细胞肥大和肝脏脂肪变性。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-18 DOI: 10.1080/01480545.2025.2534714

Jakeline Liara Teleken, Isabela Carolina Menoncin Conte, Gabriel Schorr, Larissa Glugoski, Laura Bergenthal, Jean Luca Alves, Viviane Nogaroto Vicari, Marcelo Ricardo Vicari, Rosane Aparecida Ribeiro, Maria Lúcia Bonfleur

{"title":"Pubertal atrazine exposure promotes adipocyte hypertrophy and hepatic steatosis in adult mice on a high-fat diet.","authors":"Jakeline Liara Teleken, Isabela Carolina Menoncin Conte, Gabriel Schorr, Larissa Glugoski, Laura Bergenthal, Jean Luca Alves, Viviane Nogaroto Vicari, Marcelo Ricardo Vicari, Rosane Aparecida Ribeiro, Maria Lúcia Bonfleur","doi":"10.1080/01480545.2025.2534714","DOIUrl":"https://doi.org/10.1080/01480545.2025.2534714","url":null,"abstract":"The herbicide atrazine (ATZ) has been implicated in metabolic disruptions. This study investigated the long-term consequences of pubertal ATZ-based herbicide exposure on the development of obesity in mice fed a high-fat diet (HFD) in adulthood. Male and female C57Bl/6 mice received ATZ (5 mg/kg) or water (control group) from postnatal day (PND) 30 to 60. Following puberty, all mice were fed a HFD for 90 days. Pubertal ATZ-based herbicide exposure increases food intake, specifically in male mice. While body weight, subcutaneous adiposity, and white adipose tissue (WAT) weights remained unchanged, ATZ-exposed male mice showed worsened adipocyte hypertrophy and upregulation of genes involved fat metabolism (Srebp-2, Ppar-γ, Cd36, and Adrp) in perigonadal WAT. Additionally, pubertal ATZ exposure exacerbated hepatic steatosis in both sexes, with increased ectopic fat accumulation in females correlating with increases in genes involved in fatty acid uptake and exportation (fatty acid transport protein 5 and microsomal triglyceride transfer protein). These findings provide new insights into the long-term metabolic consequences of pubertal exposure to ATZ, including exacerbated HFD-induced adiposity and hepatic steatosis. The observed sex-specific effects underscore the importance of considering pubertal windows of susceptibility to environmental disruptors and their potential impacts on adult health.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658698","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}

引用次数: 0

Topiramate exacerbates liver damage: a study on NAFLD, nitrosative stress and apoptosis. 托吡酯加重肝损伤：NAFLD、亚硝化应激和细胞凋亡的研究。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-07-18 DOI: 10.1080/01480545.2025.2533252

Sevtap Kılınç, Pelin Şahin, Zeynep Yığman, Müşerref Şeyma Ceyhan, Ayşe Meltem Sevgili

{"title":"Topiramate exacerbates liver damage: a study on NAFLD, nitrosative stress and apoptosis.","authors":"Sevtap Kılınç, Pelin Şahin, Zeynep Yığman, Müşerref Şeyma Ceyhan, Ayşe Meltem Sevgili","doi":"10.1080/01480545.2025.2533252","DOIUrl":"https://doi.org/10.1080/01480545.2025.2533252","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of obesity. Topiramate (TPM) is an anti-obesity drug. Previously, TPM showed oxidative effect to the liver. On the other hand, its effect on nitrosative stress, inflammation, and apoptosis in healthy and fatty livers remains unclear. Therefore, we aim to fill this gap. Twenty-four male Wistar albino rats were randomly assigned to four groups: Control, Diet, TPM, and Diet + TPM. The diet groups received a high-fat diet for six weeks to induce NAFLD. The TPM groups administered orally (100 mg/kg/d) for an additional 21 days. Rat livers were analyzed for NO, nitrotyrosine, TNF-α, IL-10, caspase 3 and 9, and cytochrome-c (Cyt-c). Liver sections were evaluated immunohistochemically for BAX and BCL-2 expressions. Caspase-3, Caspase-9, and Cyt-c levels were increased, and IL-10 levels were decreased in both the diet and TPM groups. When applied together, Co-administration of a high-fat diet and TPM further elevated Caspase-9 and Cyt-c levels in the Diet + TPM group. Although TNF-α levels were higher in both the diet and TPM groups, statistical significance was attained only in the diet + TPM group. TPM also increased NO and nitrotyrosine levels in both standard and high-fat diet groups. TPM causes liver tissue nitrosative stress, and increased apoptosis regardless of NAFLD. Due to the high occurrence of NAFLD in obese people, it is important to carefully evaluate using TPM as an anti-obesity medicine.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658699","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}

引用次数: 0