Melatonin Mitigates Abamectin-Induced Subacute Hematotoxicity and Hepato-Renal Toxicity in Rats by Regulating Oxidative Stress, Inflammatory Responses, and Apoptosis

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hatice Karaboduk, Caglar Adiguzel, Meltem Uzunhisarcikli, Fatma Gokce Apaydin, Yusuf Kalender
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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.

Abstract Image

褪黑素通过调节氧化应激、炎症反应和细胞凋亡减轻阿巴菌素诱导的大鼠亚急性血液毒性和肝肾毒性
阿维菌素具有很强的驱虫杀虫活性和对非靶生物的毒性作用,是一种广泛使用的农药。在这项研究中,通过生化、氧化应激、免疫组织化学、组织病理学和细胞病理学研究,评估褪黑素(10 mg/kg体重)对大鼠阿维菌素(0.5 mg/kg体重)的亚急性肝肾毒性具有有效的抗炎、抗凋亡和抗氧化作用。阿维菌素处理大鼠肝肾组织中MDA和8-OHdG水平、总氧化状态和氧化应激指数显著升高。内源抗氧化酶活性和总抗氧化能力显著降低。组织中乙酰胆碱酯酶活性、TNF-α和caspase-3免疫阳性细胞以及白细胞介素-17水平均显著降低。阿维菌素导致红细胞、血红蛋白、红细胞压积和血小板计数显著减少,白细胞计数显著增加。此外,阿维菌素增加了ALT、AST、ALP和LDH的活性,以及总胆固醇、甘油三酯、肌酐、尿酸、尿素和BUN的水平,这些被评估为血液肝肾组织的生物标志物。同时,它引起总蛋白和白蛋白水平的下降。此外,这些生化参数的改变还伴随着肝肾组织的细胞病理学和组织病理学改变。然而,外源性褪黑素的补充减少了阿维菌素引起的大鼠氧化应激,使肝肾组织的病理变化更为轻微。它还逆转了血液参数和肝肾指标的变化。总之,本研究提示外源性褪黑素补充可能通过抗炎、抗氧化和抗凋亡机制显著改善阿巴菌素诱导的大鼠肝肾损伤。
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
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.
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