Lab Anim Res.  2016 Mar;32(1):24-33. 10.5625/lar.2016.32.1.24.

Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury

Affiliations
  • 1BK21 Plus Team, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea. toxkim@jnu.ac.kr

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.

Keyword

1,3-dichloro-2-propanol; hepatotoxicity; MAPKs; NF-κB

MeSH Terms

Animals
Bilirubin
Blood Glucose
Body Weight
Caspase 3
Cholesterol
Cytokines
Glutathione
Humans
Liver
Male
Malondialdehyde
Mitogen-Activated Protein Kinases*
Oxidative Stress
Phosphorylation
Rats
Transaminases
Bilirubin
Caspase 3
Cholesterol
Cytokines
Glutathione
Malondialdehyde
Mitogen-Activated Protein Kinases
Transaminases
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