Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.
Department of Genetics, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.
J Biochem Mol Toxicol. 2023 May;37(5):e23326. doi: 10.1002/jbt.23326. Epub 2023 Feb 19.
Our experimental objective was to investigate the hepatotoxic effect of vincristine (VCR) administration in rats and determined whether combined therapy with Quercetin (Quer) ensured protection. Five groups with seven rats each were used for this purpose, and experimental groups were formulated as follows: Control group; Quer group; VCR group; VCR plus Quer 25 group; VCR plus Quer 50 group. The results showed that VCR significantly increased the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes. Besides, VCR caused considerable increases in the malondialdehyde (MDA) contents, along with significant decreases in reduced glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase enzyme activities in the rat livers. Quer treatment in VCR toxicity markedly decreased the activity of ALT, AST, ALP enzymes, and MDA contents and enhanced the activities of antioxidant enzymes. The results also showed that VCR significantly increased the levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3 and decreased the expression of Bcl2 and levels of Nrf2, HO-1, SIRT1, and PGC-1α. Compared to the VCR group, Quer treatment exhibited significantly lower levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3, and higher levels of Nrf2, HO-1, SIRT1, and PGC-1α. In conclusion, our study demonstrated that Quer could alleviate the harmful effects of VCR via activation of NRf2/HO-1 and SIRT1/PGC-1α pathways, and via attenuation of oxidative stress, apoptosis, autophagy, and NF-kB/STAT3 pathways.
我们的实验目的是研究长春新碱（VCR）给药对大鼠的肝毒性作用，并确定槲皮素（Quer）联合治疗是否能确保保护作用。为此，我们使用了五组，每组有七只大鼠，实验组的配方如下：对照组；Quer 组；VCR 组；VCR+Quer 25 组；VCR+Quer 50 组。结果表明，VCR 显著增加了丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）的活性。此外，VCR 导致丙二醛（MDA）含量显著增加，同时降低了还原型谷胱甘肽水平、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶在大鼠肝脏中的活性。Quer 在 VCR 毒性中的治疗显著降低了 ALT、AST、ALP 酶的活性和 MDA 含量，并增强了抗氧化酶的活性。结果还表明，VCR 显著增加了 NF-kB、STAT3 的水平以及 caspase 3、Bax 和 MAP LC3 的表达，并降低了 Bcl2 的表达和 Nrf2、HO-1、SIRT1 和 PGC-1α 的水平。与 VCR 组相比，Quer 治疗表现出 NF-kB、STAT3 以及 caspase 3、Bax 和 MAP LC3 的表达明显降低，而 Nrf2、HO-1、SIRT1 和 PGC-1α 的水平明显升高。总之，我们的研究表明，Quer 可以通过激活 NRf2/HO-1 和 SIRT1/PGC-1α 途径以及通过减轻氧化应激、凋亡、自噬和 NF-kB/STAT3 途径来减轻 VCR 的有害作用。
