Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats

Objectives 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 close of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 mu g/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. Key findings 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-GaIN 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 hi, 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 call 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.