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牛磺酸和 N-乙酰半胱氨酸对氟虫腈诱导损伤的肝肾保护作用:大鼠的抗氧化状态和凋亡标志物表达。

Hepatorenal protective effects of taurine and N-acetylcysteine against fipronil-induced injuries: The antioxidant status and apoptotic markers expression in rats.

机构信息

Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.

Department of Pathology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.

出版信息

Sci Total Environ. 2019 Feb 10;650(Pt 2):2063-2073. doi: 10.1016/j.scitotenv.2018.09.313. Epub 2018 Sep 25.

Abstract

Fipronil (FPN), a commonly used phenylpyrazole pesticide can induce oxidative tissue damage following hazard usage. Due to the extensive household and commercial usage of FPN, its toxic effects on mammals received considerable attention. Finding the proper antioxidant that can overcome FPN-induced damage is essential. Therefore, the present study aimed to assess the hepatorenal ameliorative outcomes of N-acetyl cysteine (NAC) and taurine (TAU) against hepatorenal damage induced by FPN in male Wistar rats. Compared to control rats, oral FPN (at a dose of 19.4 mg kg BW for five successive days) significantly increased serum activities (p ≤ 0.05) of alkaline phosphatase, lactate dehydrogenase and transaminases, in addition to total cholesterol, urea and creatinine levels. Moreover, FPN provoked oxidative damage indicated by increased malondialdehyde and nitric oxide formation and decreased glutathione concentration and activities of enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and catalase) in the hepatic and renal tissues. Furthermore, FPN administration induced overexpression of the proapoptotic (Bax), while it downregulated the expression of the anti-apoptotic (Bcl-2) protein. Interestingly, oral administration of TAU (50 mg Kg BW) and NAC (50 mg Kg BW), alone or in combination, five days prior to and five days along with FPN administration, significantly ameliorated (p ≤ 0.05) and normalized the harmful effects of FPN on serum biomarkers of hepatorenal injury, lipid peroxidation and tissue antioxidants. In conclusion, TAU and NAC, alone or in combination, provided significant hepatorenal protection against oxidative stress and apoptosis induced by FPN.

摘要

氟虫腈(FPN)是一种常用的苯吡唑类农药,在危险使用后会引起氧化组织损伤。由于 FPN 在家庭和商业中的广泛使用,其对哺乳动物的毒性作用受到了相当多的关注。寻找可以克服 FPN 诱导损伤的合适抗氧化剂是至关重要的。因此,本研究旨在评估 N-乙酰半胱氨酸(NAC)和牛磺酸(TAU)对 FPN 诱导雄性 Wistar 大鼠肝肾功能损伤的改善作用。与对照组大鼠相比,连续 5 天口服 FPN(剂量为 19.4mg/kgBW)显著增加了血清碱性磷酸酶、乳酸脱氢酶和转氨酶的活性(p≤0.05),以及总胆固醇、尿素和肌酐水平。此外,FPN 引起了氧化损伤,表现为丙二醛和一氧化氮形成增加,谷胱甘肽浓度和肝肾功能酶抗氧化剂(超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶)活性降低。此外,FPN 给药诱导了促凋亡蛋白(Bax)的过度表达,同时下调了抗凋亡蛋白(Bcl-2)的表达。有趣的是,在 FPN 给药前 5 天和给药期间连续 5 天口服 TAU(50mg/kgBW)和 NAC(50mg/kgBW),单独或联合使用,显著改善(p≤0.05)并使 FPN 对肝肾功能损伤、脂质过氧化和组织抗氧化剂的有害影响正常化。总之,TAU 和 NAC 单独或联合使用,对 FPN 诱导的氧化应激和细胞凋亡提供了显著的肝肾功能保护作用。

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