Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats.
OBJECTIVE
The protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced acute liver injury in rats were investigated.


METHODS
Wistar rats were orally administered saline (control) or one of the test compounds (caffeine, chlorogenic acid, trigonelline, nicotinic acid or eight pyrazinoic acids) at a dose of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 mug/kg)/D-GalN (250 mg/kg) 1 h after administration of the test compounds. Blood samples were collected up to 12 h after LPS/D-GalN injection, followed by determination of plasma aspartate aminotransferase, alanine aminotransferase, tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) levels.


RESULTS
Plasma aspartate aminotransferase and alanine aminotransferase levels were significantly increased after LPS/D-GalN-treatment, but were suppressed by pretreatment with caffeine (n = 5), nicotinic acid, non-substituted pyrazinoic acid or 5-methylpyrazinoic acid (n = 6, respectively) 12 h after LPS/D-GalN-treatment (P < 0.01, respectively). Moreover, the animals pretreated with these test compounds showed significantly higher survival rates (83-100%) compared with the control (23%). Only pretreatment with caffeine significantly suppressed the LPS/D-GalN induced elevation of plasma TNF-alpha levels 1 and 2 h after LPS/D-GalN-treatment (P < 0.01, respectively). Pretreatment with caffeine, nicotinic acid or non-substituted pyrazinoic acid activated the LPS/D-GalN induced elevation of plasma IL-10 levels at 1 and 2 h, although there were no statistically significant differences in IL-10 levels between control and nicotinic acid or non-substituted pyrazinoic acid treated rats.


CONCLUSIONS
The results suggest that caffeine, nicotinic acid, non-substituted pyrazinoic acid and 5-methylpyrazinoic acid can protect against LPS/D-GalN induced acute liver injury, which may be mediated by the reduction of TNF-alpha production and/or increasing IL-10 production.
Akashi
Iwao
I
Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Kagami
Keisuke
K
Hirano
Toshihiko
T
Oka
Kitaro
K
D000410:Alanine Transaminase / Q000097:blood; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury; D002726:Chlorogenic Acid / Q000494:pharmacology; D003069:Coffee / Q000737:chemistry*; D005688:Galactosamine; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides; D008107:Liver Diseases / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D009525:Niacin / Q000494:pharmacology; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000470:Alkaloids; D003069:Coffee; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009525:Niacin; D011718:Pyrazinamide; C005296:pyrazinoic acid; D002726:Chlorogenic Acid; D002110:Caffeine; C009560:trigonelline; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase