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...

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Published in:Toxicology and applied pharmacology 2010-02, Vol.242 (3), p.318-325
Main Authors: Shim, Ji-Young, Kim, Mi-Hyoung, Kim, Hyung-Doo, Ahn, Ji-Yeon, Yun, Yeon-Sook, Song, Jie-Young
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Alanine transaminase
Alanine Transaminase - metabolism
ANIMALS
ANTIOXIDANTS
Antioxidants - metabolism
Aspartate Aminotransferases - metabolism
Biological and medical sciences
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBON TETRACHLORIDE
Carbon Tetrachloride Poisoning - physiopathology
CATALASE
Chemical and Drug Induced Liver Injury - prevention & control
CHEMICAL REACTIONS
Chemokine
Chemokines - drug effects
Chemokines - metabolism
CHLORINATED ALIPHATIC HYDROCARBONS
Cytochrome P-450 CYP2E1 - genetics
Cytokine
Cytokines - drug effects
Cytokines - metabolism
DIGESTIVE SYSTEM
DISEASES
Down-Regulation - drug effects
DRUGS
ENZYMES
GLANDS
GLUTATHIONE
GROWTH FACTORS
HALOGENATED ALIPHATIC HYDROCARBONS
HISTOLOGY
INFLAMMATION
Inflammation - chemically induced
Inflammation - prevention & control
INJURIES
LEUKOCYTES
Leukocytes - drug effects
Leukocytes - metabolism
Lipid Peroxidation - drug effects
LIVER
LYMPHOKINES
Male
MAMMALS
MATERIALS
Medical sciences
MICE
Mice, Inbred BALB C
MITOGENS
NECROSIS
Necrosis - chemically induced
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
OXIDATION
Oxidative stress
Oxidative Stress - drug effects
OXIDOREDUCTASES
Panax - chemistry
Panax ginseng
PATHOLOGICAL CHANGES
PEPTIDES
PEROXIDASES
POLYPEPTIDES
Polysaccharides - isolation & purification
Polysaccharides - pharmacology
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
RODENTS
SUPEROXIDE DISMUTASE
SYMPTOMS
Toxicology
VERTEBRATES
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Summary: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-1β, IFN-γ) and chemokines (MCP-1, MIP-2β, 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.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2009.11.005