Mechanistic insights into acetamiprid-induced genotoxicity on the myocardium and potential ameliorative role of resveratrol

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2024-08-05 DOI:10.1016/j.etap.2024.104526

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

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Abstract

The current study aimed to explore the genotoxic impacts of the insecticide acetamiprid (ACP) on the myocardium and assess the ameliorative role of resveratrol (RSV). Male rats (10/group) were treated via oral route for 90 days: control; ACP (25 mg/kg); RSV (20 mg/kg); ACP+RSV. Peripheral blood micronucleus test, oxidative stress analysis, comet assay, 8-hydroxydeoxyguanosine and gene expression assessment were performed. The findings revealed that ACP has myocardial genotoxic effects, as demonstrated by increased micronucleus and 8-hydroxydeoxyguanosine formation and increased all comet parameters. Oxidative stress analysis demonstrated that ACP elevated H₂O₂ and NO levels while decreasing catalase and GST activities. Acetamiprid dysregulated the expression of genes related to oxidative stress and DNA damage response. However, RSV co-treatment resulted in significant protection against these genotoxic impacts. Resveratrol reduced DNA damage and restored the oxidative balance in the myocardium. Moreover, RSV modulated the Nrf2/HO-1 and Atm/P53 pathways, potentiating antioxidant defense and DNA repair.

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啶虫脒对心肌基因毒性的机理揭示以及白藜芦醇的潜在改善作用

本研究旨在探讨杀虫剂啶虫脒（ACP）对心肌的遗传毒性影响，并评估白藜芦醇（RSV）的改善作用。雄性大鼠（10 只/组）经口服接受为期 90 天的治疗：对照组；ACP（25 毫克/千克）；RSV（20 毫克/千克）；ACP+RSV。实验中进行了外周血微核试验、氧化应激分析、彗星试验、8-羟基脱氧鸟苷和基因表达评估。研究结果表明，ACP 有心肌基因毒性作用，表现为微核和 8-羟基脱氧鸟苷形成增加以及所有彗星参数增加。氧化应激分析表明，ACP 提高了 H2O2 和 NO 的水平，同时降低了过氧化氢酶和 GST 的活性。啶虫脒使氧化应激和 DNA 损伤反应相关基因的表达失调。然而，RSV 协同处理可显著防止这些基因毒性影响。白藜芦醇减少了 DNA 损伤，恢复了心肌的氧化平衡。此外，RSV 还调节了 Nrf2/HO-1 和 Atm/P53 通路，增强了抗氧化防御和 DNA 修复能力。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.