Zhang Zhigang, Gao Li, Cheng Yanyan, Jiang Jing, Chen Yan, Jiang Huijie, Yu Hongxiang, Shan Anshan, Cheng Baojing
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China.
Biomed Res Int. 2014;2014:617202. doi: 10.1155/2014/617202. Epub 2014 Jul 24.
Resveratrol (Rev) can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As2O3) is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As2O3 are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As2O3 treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As2O3-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As2O3-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As2O3-induced hepatotoxicity.
白藜芦醇(Rev)可改善细胞毒性化疗诱导的毒性和氧化应激。三氧化二砷(As2O3)是一种已知的细胞毒性环境毒物和强效化疗药物。然而,白藜芦醇保护肝脏免受As2O3细胞毒性作用的机制尚不清楚。因此,在本研究中,我们使用通过As2O3处理诱导肝毒性的猫模型,研究了白藜芦醇作用的相关机制。我们发现,采用临床可比剂量方案给予白藜芦醇预处理,可逆转As2O3诱导的形态学和肝脏参数变化,并导致肝功能显著改善。白藜芦醇治疗还提高了抗氧化酶的活性,并减轻了As2O3诱导的活性氧增加和丙二醛生成。此外,白藜芦醇减轻了As2O3诱导的还原型谷胱甘肽与氧化型谷胱甘肽比值降低以及肝脏组织中砷的潴留。这些发现有助于更好地理解白藜芦醇调节As2O3诱导的肝功能和组织形态变化的机制。它们还为临床使用白藜芦醇降低As2O3诱导的肝毒性提供了更有力的理论依据。