Dai Chongshan, Li Daowen, Gong Lijing, Xiao Xilong, Tang Shusheng
College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
Sport Science Research Center, Beijing Sport University, 48 Xinxi Road, Haidian District, Beijing 100084, China.
Molecules. 2016 Aug 22;21(8):1061. doi: 10.3390/molecules21081061.
Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications.
呋喃唑酮(FZD)是一种合成的硝基呋喃衍生物,已被广泛用作抗菌和抗原虫药物。最近,FZD的潜在毒性引起了关注,但其机制仍不清楚。本研究旨在探讨姜黄素对FZD诱导的人肝细胞L02细胞毒性的保护作用及其潜在机制。结果表明,姜黄素预处理显著改善了FZD诱导的氧化应激,表现为活性氧(ROS)和丙二醛生成减少,超氧化物歧化酶、过氧化氢酶活性和谷胱甘肽含量增加。此外,姜黄素预处理显著改善了FZD引起的线粒体膜电位丧失、半胱天冬酶-9和-3的激活以及细胞凋亡。碱性彗星试验表明,姜黄素以剂量依赖的方式显著降低了FZD诱导的DNA损伤。姜黄素预处理持续且显著下调了p53、Bax、半胱天冬酶-9和-3的mRNA表达水平,并上调了Bcl-2的mRNA表达水平。综上所述,这些结果表明姜黄素通过抑制氧化应激和线粒体途径来保护细胞免受FZD诱导的DNA损伤和细胞凋亡。我们的研究表明,姜黄素可能是一种有前途的与FZD联合使用的药物,可在临床应用中降低FZD相关的毒性。