title: Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury.
abstract: In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by an increase in serum aminotransferases, total cholesterol, and total bilirubin levels and a decrease in serum glucose concentration in a dose-dependent manner with corresponding histopathological changes in the hepatic tissues. The significant increase in malondialdehyde content and the significant decrease in glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro-2-propanol-induced hepatic damage was mediated through oxidative stress, which caused a dose-dependent increase of hepatocellular apoptotic changes in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical analysis for caspase-3. The phosphorylation of mitogen-activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2-propanol induced an inflammatory response through activation of nuclear factor-kappa B signaling that coincided with the induction of pro-inflammatory mediators or cytokines in a dose-dependent manner. Taken together, these results demonstrate that hepatotoxicity may be related to oxidative stress-mediated activation of mitogen-activated protein kinases and nuclear factor-kappa B-mediated inflammatory response.
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Lee
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Je-Won
authors.initials: JW
authors.lastname: Ko
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Sung-Hyeuk
authors.initials: SH
authors.lastname: Park
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Shin
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
keywords: 1,3-dichloro-2-propanol; MAPKs; NF-κB; hepatotoxicity