Resveratrol Mitigates Acetamiprid-Induced Cardiotoxicity in Rats via Modulation of Jak/Stat, p38 Mapk and mTOR Signaling Pathways

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-05-27 DOI:10.1002/jbt.70321

Rehab E. Abdelrahman, Mohamed S. Hassan, Ashraf M. Morgan, Marwa A. Ibrahim, Eman I. Hassanen

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Abstract

Acetamiprid (ACP) is a novel neonicotinoid insecticide used frequently to eradicate insect pests. Resveratrol (RSV) is a polyphenol used as a potential antioxidant, anti-inflammatory and antiapoptotic compound. The current research aimed to investigate the modulation of Jak/Stat, p38 Mapk, and mTOR signaling pathways by RSV in ACP-induced cardiotoxicity. Four equal groups of male rats (10 rats each) were treated daily for 90 days via oral intubation. Group 1 was the control; Group 2 received ACP (25 mg/kg b. wt); Group 3 received RSV (20 mg/kg b. wt); and Group 4 received both ACP and RSV. Gene expression and tissue proteins were analyzed in the heart while biochemical changes were estimated in serum. Histopathological and histochemical alterations of the cardiac tissues were also investigated. ACP administration showed elevations of mRNA expression of the inflammation-related genes (Jak, Stat, NF-κB, p38 Mapk) and tissue proteins (mTOR and TNF-α) in the myocardium. Significant serum high sensitivity C-reactive protein (hs-CRP) level and lactate dehydrogenase (LDH) activity were also recorded. Histopathology and immunohistochemistry showed myocardial infarction and inflammatory cell infiltration besides increased IL-6 protein expression. On the other hand, RSV treatment alleviated ACP-induced cardiotoxic actions and modulated the expression levels of the inflammation-related genes signaling pathways.

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白藜芦醇通过调节Jak/Stat， p38 Mapk和mTOR信号通路减轻对乙酰米虫啉诱导的大鼠心脏毒性

啶虫脒（Acetamiprid， ACP）是一种常用的新型新烟碱类杀虫剂。白藜芦醇（RSV）是一种多酚，被用作潜在的抗氧化、抗炎和抗凋亡化合物。本研究旨在探讨RSV在acp诱导的心脏毒性中对Jak/Stat、p38 Mapk和mTOR信号通路的调节作用。4组雄性大鼠，每组10只，每日口服插管治疗90 d。第一组为对照组；2组给予ACP (25 mg/kg b. wt)；3组注射RSV (20 mg/kg b. wt)；第4组同时给予ACP和RSV治疗。分析心脏基因表达和组织蛋白，测定血清生化变化。并观察了心脏组织的组织病理学和组织化学变化。ACP组心肌炎症相关基因（Jak、Stat、NF-κB、p38 Mapk）和组织蛋白（mTOR、TNF-α） mRNA表达升高。血清高敏c反应蛋白（hs-CRP）水平和乳酸脱氢酶（LDH）活性均有显著差异。组织病理学和免疫组化检查显示心肌梗死、炎症细胞浸润，IL-6蛋白表达升高。另一方面，RSV治疗减轻acp诱导的心脏毒性作用，并调节炎症相关基因信号通路的表达水平。

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来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

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.