Olayinka Ebenezer Tunde, Ore Ayokanmi, Adeyemo Oluwatobi Adewumi, Ola Olaniyi Solomon
Biochemistry Unit, Department of Chemical Sciences, Ajayi Crowther University, Oyo, Oyo State, Nigeria.
J Xenobiot. 2016 Aug 26;6(1):6092. doi: 10.4081/xeno.2016.6092. eCollection 2016 Jun 10.
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.
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。