ALL-TRANS-RETINOIC ACID SUPPRESSES LIVER-INJURY INDUCED BY PROPIONIBACTERIUM-ACNES AND LIPOPOLYSACCHARIDE IN RATS

All-traits retinoic acid (ATRA) has been reported to exert major effec ts on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage -associated liver injury induced by Propionibacterium acnes and lipopo lysaccharide (LPS) in rats. All-traits retinoic acid administration al leviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h afte r, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134 +/- 119 IU/L and 7 2.7%) compared with the control group (713 +/- 411 IU/L and 18.2%; P < 0.05). Histological findings supported these results. These effects m ay be due to suppression of tumour necrosis factor-alpha (TNF-alpha) a nd superoxide anions produced by activated macrophages. Serum levels o f TNF-alpha 1 h after LPS administration were significantly lower in t he ATRA-treated group (60.5 +/- 7.0 ng/mL) as compared with the contro l group (105.2 +/- 39.3 ng/mL; P < 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, a lso suggested suppression of the release of superoxide anions from hep atic macrophages. These results suggest that ATRA acts as an immunomod ulator in liver injury by suppressing the activation of liver macropha ges.