Effects of CH-100, a chinese herbal medicine, on acute concanavalin A-mediated hepatitis in control and alcohol-fed rats.
BACKGROUND
Administration of concanavalin A (Con A) leads to acute hepatitis that involves T-cell activation and inflammatory mediator production in mice and rats. We examined the role of CH-100, a Chinese herbal medicine previously trialed in human hepatitis C, in the prevention of Con A-related, T-cell-mediated, acute liver injury in rats.


METHODS
Female Wistar rats were fed 40% ethanol, 2% sucrose, or isocaloric sucrose for 8 weeks. At the same time, these animals were fed either the Chinese herbal medicine CH-100 (4 tablets/kg body weight/ day) or placebo in chow daily. Blood from the tail vein was collected for endotoxin (lipopolysaccharide) assay at 0, 4, and 8 weeks of ethanol consumption. Twenty-four hours after injection of Con A (20 mg/kg body weight) or phosphate-buffered saline, blood from the tail vein was collected for alanine aminotransferase and tumor necrosis factor (TNF)-alpha assays. Liver-associated CD4+ T cells were isolated from liver perfusates and then cultured with Con A (5 microg/ml) at 37 degrees C for 24 hr. Supernatants were harvested for TNF-alpha assay. The proportion of CD4+ T cells in blood and liver perfusates was measured. Liver samples were collected for histopathological analysis.


RESULTS
Lipopolysaccharide levels were significantly reduced in CH-100-treated ethanol-fed rats compared with placebo-treated rats. After Con A injection, alanine aminotransferase levels were lower at 12 and 24 hr in herb-treated rats compared with placebo-treated rats. Furthermore, serum TNF-alpha levels were lower in ethanol-fed rats on herbal treatment. A significant decrease in TNF-alpha production by liver-associated CD4+ T cells in culture was observed in CH-100-treated ethanol-fed rats. CH-100 treatment was associated with a decreased percentage of CD4+ cells in both blood and liver perfusate in all groups. Herb-treated rats displayed markedly less hepatic necrosis and a reduced CD4+ T-cell infiltrate in portal areas than did placebo-fed rats.


CONCLUSIONS
The results demonstrate that CH-100 modified the T-cell response to Con A injection. The effect was more marked in ethanol-fed rats, which suggests a possible role for CH-100 in treating alcoholic liver disease.
Batey
R
R
Department of Gastroenterology, John Hunter Hospital Newcastle, NSW, Australia.
Cao
Q
Q
Pang
G
G
Clancy
R L
RL
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000009:adverse effects; D003208:Concanavalin A; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D006520:Hepatitis, Animal / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D002492:Central Nervous System Depressants; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D000431:Ethanol; D000410:Alanine Transaminase