title: Protective effects of the bioactive natural product N-trans-Caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin.
abstract: In our searching for novel antioxidants from natural sources, N-trans-Caffeoyldopamine which was from natural product was found to be a potential compound for its remarkable antioxidant activity. Isoniazid (INH) and Rifampicin (RFP) is widely used for the treatment of Tuberculosis (TB) as the first line drugs, have been known to be potentially hepatotoxic and may lead to drug-induced liver injury. Oxidative stress has been regarded as the major mechanism of the hepatotoxicity. Therefore, in this study, the possible protective effects of N-trans-Caffeoyldopamine was investigated in the hepatotoxicity caused by INH and RFP in rats. Results showed that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and hepatic malondialdehyde (MDA) content were reduced dramatically, and hepatic superoxide dismutase (SOD) activity and glutathione (GSH) content were restored remarkably by N-trans-Caffeoyldopamine co-administration, as compared to the INH-RFP treated rats (p<0.01). Moreover, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly ameliorated by the treatment. It is therefore suggested that N-trans-Caffeoyldopamine can provide a definite protective effect against acute hepatic injury caused by INH and RFP in rats, which may mainly be associated with its antioxidative effect. Mechanisms studies indicated that it inhibited the lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation.
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Wu
authors.affiliation: The First Hospital of Lanzhou University, People's Republic of China.
authors.forename: Zhong-Tian
authors.initials: ZT
authors.lastname: Bai
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Yang
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: De-Juan
authors.initials: DJ
authors.lastname: Zhi
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Du
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China. Electronic address: wuzhrong@163.com.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Li
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry* / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007538:Isoniazid / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D015394:Molecular Structure; D051381:Rats; D012293:Rifampin / Q000633:toxicity*
chemical_list: D001688:Biological Products; D002109:Caffeic Acids; C506152:N-caffeoyldopamine; D007538:Isoniazid; D012293:Rifampin; D004298:Dopamine
keywords: Antioxidant activity; CYP2E1; Hepatoprotective effect; INH and RFP; N-trans-Caffeoyldopamine