Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury.
- Author:
In Chul LEE
1
;
Sang Min LEE
;
Je Won KO
;
Sung Hyeuk PARK
;
In Sik SHIN
;
Changjong MOON
;
Sung Ho KIM
;
Jong Choon KIM
Author Information
- Publication Type:Original Article
- Keywords: 1,3-dichloro-2-propanol; hepatotoxicity; MAPKs; NF-κB
- MeSH: Animals; Bilirubin; Blood Glucose; Body Weight; Caspase 3; Cholesterol; Cytokines; Glutathione; Humans; Liver; Male; Malondialdehyde; Mitogen-Activated Protein Kinases*; Oxidative Stress; Phosphorylation; Rats; Transaminases
- From:Laboratory Animal Research 2016;32(1):24-33
- CountryRepublic of Korea
- Language:English
- 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.
