Navid Omidifar, Ahmad Gholami, Mansoureh Shokripour, Mohammad Ali Nourani, Milad Mohkam, Seyyed Mojtaba Mousavi, Seyyed Alireza Hashemi, Bagher Khorram, Amir Nili Ahmadabadi, Mahintaj Dara
{"title":"黄嘌呤衍生物对三氧化二砷诱导的小鼠肝脏和肾脏组织氧化应激的保护作用","authors":"Navid Omidifar, Ahmad Gholami, Mansoureh Shokripour, Mohammad Ali Nourani, Milad Mohkam, Seyyed Mojtaba Mousavi, Seyyed Alireza Hashemi, Bagher Khorram, Amir Nili Ahmadabadi, Mahintaj Dara","doi":"10.1055/a-2247-5232","DOIUrl":null,"url":null,"abstract":"<p><p>In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"133-144"},"PeriodicalIF":1.7000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.\",\"authors\":\"Navid Omidifar, Ahmad Gholami, Mansoureh Shokripour, Mohammad Ali Nourani, Milad Mohkam, Seyyed Mojtaba Mousavi, Seyyed Alireza Hashemi, Bagher Khorram, Amir Nili Ahmadabadi, Mahintaj Dara\",\"doi\":\"10.1055/a-2247-5232\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.</p>\",\"PeriodicalId\":11451,\"journal\":{\"name\":\"Drug Research\",\"volume\":\" \",\"pages\":\"133-144\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1055/a-2247-5232\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/a-2247-5232","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
本研究探讨了作为黄嘌呤衍生物的喷托塞林(PTX)对三氧化二砷(ATO)诱导的小鼠肝肾损伤的保护作用。研究人员将 36 只小鼠分为 6 组,分别腹腔注射生理盐水、ATO、PTX 或其组合,为期四周。对血样进行血清生化分析,同时对肝组织进行组织病理学变化检查,并通过实时 PCR 评估氧化应激标记物和抗氧化基因的表达。暴露于 ATO 会明显增加血清指标(肌酐、谷丙转氨酶、尿素氮、谷草转氨酶、谷草转氨酶),并诱发肝脏组织病理学变化。此外,它还会升高肾脏和肝脏的一氧化氮(NO)和脂质过氧化(LPO)水平,降低抗氧化酶(CAT、GSR、GPx、MPO、SOD)、总硫醇基团(TTGs)和总抗氧化能力(TAC)的表达。相反,PTX 治疗可有效降低血清肝脏和肾脏指标,改善抗氧化指标,并诱导组织病理学改变。值得注意的是,PTX 对肾脏和肝脏的 NO 水平没有明显影响。这些研究结果表明,PTX 在减轻各种损伤(包括暴露于 ATO)引起的肝脏和急性肾脏损伤方面具有治疗潜力。
Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.
In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.
期刊介绍:
Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.