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

Abstract 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 dose of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 μg/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 α (TNF-α) 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-GalN induced elevation of plasma TNF-α 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-α production and/or increasing IL-10 production.