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阿托伐他汀对链脲佐菌素诱导的糖尿病大鼠氧化应激的保护作用与其降脂作用无关。

Protective effect of atorvastatin on oxidative stress in streptozotocin-induced diabetic rats independently their lipid-lowering effects.

机构信息

Department of Pharmacology, Faculty of Pharmacy, İnönü University, Malatya, Turkey.

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İnönü University, Malatya, Turkey.

出版信息

J Biochem Mol Toxicol. 2019 May;33(5):e22295. doi: 10.1002/jbt.22295. Epub 2019 Jan 18.

Abstract

In the present study, we investigate the effects of atorvastatin on the lipid profile, oxidative stress, and liver enzyme markers, and its protective activity against diabetic complications, in streptozotocin (STZ)-induced diabetic rats. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high-density lipoprotein (HDL) levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, were measured 7 weeks after the administration of STZ and atorvastatin. Thiobarbituric acid reactive substances (TBARS), non-protein associated sulfhydryl (NP-SH), total sulfhydryl (T-SH), and nitric oxide (NO) levels were measured to evaluate oxidative stress. Atorvastatin was found to inhibit ALT and AST activities and to reduce FBG levels in rats with STZ-induced diabetes. Moreover, atorvastatin treatment significantly reduced lipid peroxidation in kidney, heart, and eye tissues (P < 0.001, for all), and resulted in a significant increase in NP-SH levels in brain tissues (P < 0.001). Total NO and nitrate levels increased significantly after atorvastatin treatment (P < 0.01). Our results revealed that atorvastatin has a protective effect against STZ-induced oxidative damage by reducing TBARS levels and increasing NP-SH levels, has a hepatoprotective effect by decreasing ALT and AST activities. It also shows the antihyperglycemic activity by lowering FBG levels.

摘要

在本研究中,我们研究了阿托伐他汀对血脂谱、氧化应激和肝酶标志物的影响,以及其对链脲佐菌素(STZ)诱导的糖尿病大鼠糖尿病并发症的保护作用。在给予 STZ 和阿托伐他汀 7 周后,测量空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)和高密度脂蛋白(HDL)水平,以及丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)酶活性。测量硫代巴比妥酸反应物质(TBARS)、非蛋白结合巯基(NP-SH)、总巯基(T-SH)和一氧化氮(NO)水平,以评估氧化应激。阿托伐他汀被发现可抑制 STZ 诱导的糖尿病大鼠的 ALT 和 AST 活性,并降低 FBG 水平。此外,阿托伐他汀治疗可显著降低肾脏、心脏和眼部组织中的脂质过氧化(P<0.001,全部),并导致脑组织中 NP-SH 水平显著增加(P<0.001)。阿托伐他汀治疗后总 NO 和硝酸盐水平显著增加(P<0.01)。我们的结果表明,阿托伐他汀通过降低 TBARS 水平和增加 NP-SH 水平对 STZ 诱导的氧化损伤具有保护作用,通过降低 ALT 和 AST 活性具有肝保护作用。它还通过降低 FBG 水平表现出抗高血糖活性。

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