Mechanism of salutary effects of melatonin-mediated liver protection after trauma-hemorrhage: p38 MAPK-dependent iNOS/HIF-1α pathway

Trauma-hemorrhage resulted in a significant decrease in liver p38 MAPK activation and increase in inducible nitrite oxide synthase (iNOS) and hypoxia-inducible factor (HIF)-1α expression. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression, which was abolished by coadministration of SB203580 or luzindole. Melatonin prevents trauma-hemorrhage-induced liver injury in rats via the melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway.