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没食子酸对甲氨蝶呤诱导的大鼠肝毒性和肾毒性的改善作用

Ameliorative Effect of Gallic Acid on Methotrexate-Induced Hepatotoxicity and Nephrotoxicity in Rat.

作者信息

Olayinka Ebenezer Tunde, Ore Ayokanmi, Adeyemo Oluwatobi Adewumi, Ola Olaniyi Solomon

机构信息

Biochemistry Unit, Department of Chemical Sciences, Ajayi Crowther University, Oyo, Oyo State, Nigeria.

出版信息

J Xenobiot. 2016 Aug 26;6(1):6092. doi: 10.4081/xeno.2016.6092. eCollection 2016 Jun 10.

Abstract

We investigated the protective effect of gallic acid (GA) against methotrexate (MTX)-induced hepatotoxicity and nephrotoxicity. Male Wistar rats were randomized into five groups ( = 6/group): I, control; II, MTX-treated for seven days; III, pre-treated with GA for seven days, followed by MTX for seven days; IV, co-treated with MTX and GA for seven days and V, GA for seven days. MTX caused a significant increase (P<0.05) in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (Bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase) when compared with control. Furthermore, MTX caused a significant decrease in the activities of hepatic enzymic antioxidants (superoxide dismutase, catalase, glutathione S-transferase) and nonenzymic antioxidants (Vitamin C and glutathione), followed by a significant increase in hepatic malondialdehyde content. However, pre-treatment and co-treatment with gallic acid ameliorated the MTX-induced biochemical changes observed. Taken together, GA protected against MTX-induced hepatotoxicity and nephrotoxicity in rats, by reducing the impact of oxidative damage to tissues.

摘要

我们研究了没食子酸(GA)对甲氨蝶呤(MTX)诱导的肝毒性和肾毒性的保护作用。将雄性Wistar大鼠随机分为五组(每组n = 6):I组,对照组;II组,用MTX处理7天;III组,先用GA预处理7天,然后用MTX处理7天;IV组,MTX与GA联合处理7天;V组,用GA处理7天。与对照组相比,MTX导致肾毒性(尿素、肌酐)和肝毒性(胆红素、碱性磷酸酶、天冬氨酸转氨酶、丙氨酸转氨酶、γ-谷氨酰转移酶)的血浆生物标志物显著增加(P<0.05)。此外,MTX导致肝脏酶促抗氧化剂(超氧化物歧化酶、过氧化氢酶、谷胱甘肽S-转移酶)和非酶促抗氧化剂(维生素C和谷胱甘肽)的活性显著降低,随后肝脏丙二醛含量显著增加。然而,用没食子酸预处理和联合处理改善了所观察到的MTX诱导的生化变化。综上所述,GA通过减少氧化损伤对组织的影响,保护大鼠免受MTX诱导的肝毒性和肾毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9cd/6324488/254d2209d33b/xeno-6-1-6092-g001.jpg

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