title: Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China. daichongshan@163.com.
authors.forename: Chongshan
authors.initials: C
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China. lidaowen123.fff@163.com.
authors.forename: Daowen
authors.initials: D
authors.lastname: Li
authors.affiliation: Sport Science Research Center, Beijing Sport University, 48 Xinxi Road, Haidian District, Beijing 100084, China. argun@126.com.
authors.forename: Lijing
authors.initials: L
authors.lastname: Gong
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China. xiaoxilong1958@163.com.
authors.forename: Xilong
authors.initials: X
authors.lastname: Xiao
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China. tssfj@cau.edu.cn.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D005664:Furazolidone / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D005664:Furazolidone; D013482:Superoxide Dismutase; D005978:Glutathione; D003474:Curcumin
keywords: DNA damage; curcumin; furazolidone; mitochondrial pathway; oxidative stress