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三唑酮对雄性 Wistar 大鼠肾脏的氧化应激、DNA 损伤和凋亡诱导作用。

Oxidative stress, DNA damage and apoptosis induced by tebuconazole in the kidney of male Wistar rat.

机构信息

University of Monastir, Faculty of Dental Medicine of Monastir, Laboratory for Research on Biologically Compatible Compounds, LR01SE17, Rue Avicenne, 5000, Monastir, Tunisia.

University of Monastir, Faculty of Dental Medicine of Monastir, Laboratory for Research on Biologically Compatible Compounds, LR01SE17, Rue Avicenne, 5000, Monastir, Tunisia; University of Sousse, Faculty of Medicine of Sousse, Rue Mohamed Karoui, 4000, Tunisia.

出版信息

Chem Biol Interact. 2020 Oct 1;330:109114. doi: 10.1016/j.cbi.2020.109114. Epub 2020 Jul 28.

DOI:10.1016/j.cbi.2020.109114
PMID:32735800
Abstract

Tebuconazole (TEB) is a broad-spectrum conazole fungicide that has been used in agriculture in the control of foliar and soil-borne diseases of many crops. The present study has investigated the adverse effects of subchronic exposure to TEB on the kidney of male rats. Animals were divided into four equal groups and treated with TEB at increasing doses 0.9, 9 and 27 mg/kg body weight for 28 consecutive days. The results showed that TEB induced oxidative stress in the kidney demonstrated by an increase in malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP) levels and DNA damage, as compared to the controls. Furthermore, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities were increased in the renal tissue of treated rats. Moreover, significant decrease in reduced glutathione (GSH) content in TEB-treated rats was observed, while oxidized glutathione (GSSG) levels were increased, thus a marked fall in GSH/GSSG ratio was registered in the kidney. Glutathione reductase (GR) activity showed a significant increase after TEB exposure. Moreover, TEB down-regulated the expression of Bcl2 and up-regulated the expression of Bax and caspase 3, which triggered apoptosis via the Bax/Bcl2 and caspase pathway. Also, TEB administration resulted in altered biochemical indicators of renal function and varying lesions in the overall histo-architecture of renal tissues. Taken together, our findings brought into light the renal toxicity induced by TEB, which was found to be significant at low doses.

摘要

戊唑醇(TEB)是一种广谱唑类杀菌剂,已在农业中用于防治许多作物的叶面和土壤病害。本研究调查了亚慢性接触 TEB 对雄性大鼠肾脏的不良影响。动物分为四组,分别用 0.9、9 和 27mg/kg 体重的 TEB 连续 28 天处理。结果表明,TEB 诱导肾脏氧化应激,丙二醛(MDA)、蛋白质羰基(PC)、高级氧化蛋白产物(AOPP)水平和 DNA 损伤增加,与对照组相比。此外,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)在处理大鼠的肾组织中活性增加。此外,在 TEB 处理的大鼠中观察到还原型谷胱甘肽(GSH)含量显著下降,而氧化型谷胱甘肽(GSSG)水平升高,因此肾脏中 GSH/GSSG 比值明显下降。谷胱甘肽还原酶(GR)活性在 TEB 暴露后显著增加。此外,TEB 下调 Bcl2 的表达,上调 Bax 和 caspase 3 的表达,通过 Bax/Bcl2 和 caspase 途径引发细胞凋亡。此外,TEB 给药导致肾功能生化指标改变和肾脏组织整体组织学结构的不同病变。总之,我们的研究结果揭示了 TEB 引起的肾脏毒性,在低剂量时就发现其具有显著作用。

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