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芬普酯亚慢性暴露通过破坏脂质谱、诱导氧化应激和 DNA 损伤,导致 Wistar 大鼠多器官毒性。

Subchronic exposure to fenpyroximate causes multiorgan toxicity in Wistar rats by disrupting lipid profile, inducing oxidative stress and DNA damage.

机构信息

Laboratory of Research on Biologically Compatible Compounds, LR01SE17, University of Monastir, Faculty of Dental Medicine, Monastir, Tunisia.

Faculty of Science of Gafsa, University of Gafsa, Gafsa, Tunisia.

出版信息

Biomarkers. 2024 Mar;29(2):68-77. doi: 10.1080/1354750X.2024.2313663. Epub 2024 Feb 5.

DOI:10.1080/1354750X.2024.2313663
PMID:38299991
Abstract

BACKGROUND

Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain in mites. Data concerning mammalian toxicity of this acaricide are limited; thus the aim of this work was to explore FEN toxicity on Wistar rats, particularly on cardiac, pulmonary, and splenic tissues and in bone marrow cells.

METHODS

rats were treated orally with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 days. After treatment, we analyzed lipid profile, oxidative stress and DNA damage in rat tissues.

RESULTS

FEN exposure increased creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, elevated total cholesterol (T-CHOL), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) concentrations, while decreasing high-density lipoprotein cholesterol (HDL-C). It inhibited acetylcholinesterase (AChE) activity, enhanced lipid peroxidation, protein oxidation, and modulated antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase). Comet assay indicated that FEN induced a dose-dependent DNA damage, contrasting with the micronucleus test showing no micronuclei formation. Nonetheless, FEN exhibited cytotoxicity to bone marrow cells, as evidenced by a reduction in the number of immature erythrocytes among total cells.

CONCLUSION

FEN appears to carry out its genotoxic and cytotoxic activities most likely through an indirect pathway that involves oxidative stress.

摘要

背景

苯氧威(FEN)是一种杀螨剂,可抑制螨虫中线粒体呼吸链复合物 I。关于这种杀螨剂对哺乳动物的毒性的数据有限;因此,本工作旨在研究 FEN 对 Wistar 大鼠的毒性,特别是对心脏、肺和脾组织以及骨髓细胞的毒性。

方法

大鼠经口给予 FEN,剂量分别为 1、2、4 和 8mg/Kg bw,连续 28 天。治疗后,分析大鼠组织中的脂质谱、氧化应激和 DNA 损伤。

结果

FEN 暴露增加肌酸磷酸激酶(CPK)和乳酸脱氢酶(LDH)的活性,升高总胆固醇(T-CHOL)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)浓度,同时降低高密度脂蛋白胆固醇(HDL-C)。它抑制乙酰胆碱酯酶(AChE)的活性,增强脂质过氧化、蛋白质氧化,并调节抗氧化酶的活性(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽 S-转移酶)。彗星试验表明 FEN 诱导了剂量依赖性的 DNA 损伤,与微核试验形成对比,微核试验未显示形成微核。尽管如此,FEN 对骨髓细胞表现出细胞毒性,这表现为幼稚红细胞在总细胞中的数量减少。

结论

FEN 似乎通过涉及氧化应激的间接途径发挥其遗传毒性和细胞毒性作用。

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