Melatonin Mitigates Abamectin-Induced Subacute Hematotoxicity and Hepato-Renal Toxicity in Rats by Regulating Oxidative Stress, Inflammatory Responses, and Apoptosis
{"title":"Melatonin Mitigates Abamectin-Induced Subacute Hematotoxicity and Hepato-Renal Toxicity in Rats by Regulating Oxidative Stress, Inflammatory Responses, and Apoptosis","authors":"Hatice Karaboduk, Caglar Adiguzel, Meltem Uzunhisarcikli, Fatma Gokce Apaydin, Yusuf Kalender","doi":"10.1002/jbt.70512","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Abamectin is a widely used pesticide due to its strong anthelmintic and insecticidal activity and has toxic effects on nontarget organisms. In this study, melatonin (10 mg/kg body weight), which has potent anti-inflammatory, antiapoptotic, and antioxidant effects against subacute hepato-renal toxicity of abamectin (0.5 mg/kg body weight) in rats, was evaluated for its potential to alleviate organ damage by biochemical, oxidative stress, immunohistochemical, histopathological, and cytopathological studies. In hepato-renal tissues of abamectin-treated rats, MDA and 8-OHdG levels, total oxidant status, and oxidative stress index significantly increased. In contrast, endogenous antioxidant enzyme activities and total antioxidant status decreased significantly. A significant decrease in acetylcholinesterase activity, TNF-α and caspase-3 immunopositive cells, and interleukin-17 levels were also detected in the tissues. Abamectin caused a substantial reduction in red blood cell, hemoglobin, hematocrit, and platelet counts and significantly increased white blood cell count. In addition, abamectin increased the activities of ALT, AST, ALP, and LDH, and the levels of total cholesterol, triglyceride, creatinine, uric acid, urea, and BUN, which are evaluated as biomarkers of blood hepato-renal tissues. At the same time, it caused a decrease in the levels of total protein and albumin. In addition, these changing biochemical parameters are accompanied by cytopathological and histopathological changes in hepato-renal tissues. However, exogenous melatonin supplementation reduced the oxidative stress caused by abamectin in rats and caused the pathological changes in hepato-renal tissues to be observed more mildly. It also reversed the changes in blood parameters and hepato-renal markers. In conclusion, this study suggests that exogenous melatonin supplementation may help significantly ameliorate abamectin-induced hepato-renal injury in rats through anti-inflammatory, antioxidant, and antiapoptotic mechanisms.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70512","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abamectin is a widely used pesticide due to its strong anthelmintic and insecticidal activity and has toxic effects on nontarget organisms. In this study, melatonin (10 mg/kg body weight), which has potent anti-inflammatory, antiapoptotic, and antioxidant effects against subacute hepato-renal toxicity of abamectin (0.5 mg/kg body weight) in rats, was evaluated for its potential to alleviate organ damage by biochemical, oxidative stress, immunohistochemical, histopathological, and cytopathological studies. In hepato-renal tissues of abamectin-treated rats, MDA and 8-OHdG levels, total oxidant status, and oxidative stress index significantly increased. In contrast, endogenous antioxidant enzyme activities and total antioxidant status decreased significantly. A significant decrease in acetylcholinesterase activity, TNF-α and caspase-3 immunopositive cells, and interleukin-17 levels were also detected in the tissues. Abamectin caused a substantial reduction in red blood cell, hemoglobin, hematocrit, and platelet counts and significantly increased white blood cell count. In addition, abamectin increased the activities of ALT, AST, ALP, and LDH, and the levels of total cholesterol, triglyceride, creatinine, uric acid, urea, and BUN, which are evaluated as biomarkers of blood hepato-renal tissues. At the same time, it caused a decrease in the levels of total protein and albumin. In addition, these changing biochemical parameters are accompanied by cytopathological and histopathological changes in hepato-renal tissues. However, exogenous melatonin supplementation reduced the oxidative stress caused by abamectin in rats and caused the pathological changes in hepato-renal tissues to be observed more mildly. It also reversed the changes in blood parameters and hepato-renal markers. In conclusion, this study suggests that exogenous melatonin supplementation may help significantly ameliorate abamectin-induced hepato-renal injury in rats through anti-inflammatory, antioxidant, and antiapoptotic mechanisms.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.