Open AccessProtective effects of coffee‐derived compounds on lipopolysaccharide/d‐galactosamine induced acute liver injury in rats
Author(s) -
Akashi Iwao,
Kagami Keisuke,
Hirano Toshihiko,
Oka Kitaro
Publication year - 2009
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/jpp.61.04.0009
Subject(s) - lipopolysaccharide , galactosamine , liver injury , pharmacology , chemistry , medicine , anesthesia , biochemistry , glucosamine
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.