Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response.
The aim of the present study was to evaluate immunomodulator ginsan, a polysaccharide extracted from Panax ginseng, on carbon tetrachloride (CCl(4))-induced liver injury. BALB/c mice were injected i.p. with ginsan 24 h prior to CCl(4) administration. Serum liver enzyme levels, histology, expression of antioxidant enzymes, and several cytokines/chemokines were subsequently evaluated. Ginsan treatment markedly suppressed the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and hepatic histological necrosis increased by CCl(4) treatment. Ginsan inhibited CCl(4) induced lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation. The hepatoprotective effect of ginsan was attributed to induction of anti-oxidant protein contents, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) as well as restoration of the hepatic glutathione (GSH) concentration. The marked increase of proinflammatory cytokines (IL-1beta, IFN-gamma) and chemokines (MCP-1, MIP-2beta, KC) in CCl(4) treated mice was additionally attenuated by ginsan, thereby preventing leukocyte infiltration and local inflammation. Our results suggest that ginsan effectively prevent liver injury, mainly through downregulation of oxidative stress and inflammatory response.
Shim
Ji-Young
JY
Laboratory of Radiation Cancer Sciences, Korea Institute of Radiological & Medical Sciences, 215-4, Gongneung-dong, Nowon-ku, Seoul 139-706, Korea.
Kim
Mi-Hyoung
MH
Kim
Hyung-Doo
HD
Ahn
Ji-Yeon
JY
Yun
Yeon-Sook
YS
Song
Jie-Young
JY
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000503:physiopathology*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D018925:Chemokines / Q000187:drug effects / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects*; D005894:Panax / Q000737:chemistry*; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*
D000975:Antioxidants; D018925:Chemokines; D016207:Cytokines; D011134:Polysaccharides; C111520:ginsan; D019392:Cytochrome P-450 CYP2E1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase