Laboraroty Animal Research

Korean Association for Laboratory Animal Science (한국실험동물학회)
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Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury

  • Lee, In-Chul (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University) ;
  • Lee, Sang-Min (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University) ;
  • Ko, Je-Won (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University) ;
  • Park, Sung-Hyeuk (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University) ;
  • Shin, In-Sik (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University) ;
  • Moon, Changjong (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Ho (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Jong-Choon (BK21 Plus Team, College of Veterinary Medicine, Chonnam National University)
  • Received : 2016.02.16
  • Accepted : 2016.03.03
  • Published : 2016.03.30
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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.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea, Animal Medical Institute of Chonnam National University

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