Nitric oxide in an acute liver injury model

Abstract

We investigated whether a high level of nitric oxide (NO) is protective or injurious in acute liver injury. An acute phase ICR mice model was used by injecting CC1, with or without NO inhibitors (SMT and L-NIL) and NO donor (SNP). Blood and liver tissues were collected. Immunocytochemistry, RT-PCR, Western Blotting, EMSA, semm ALT and total 8-isoprostane analyses were performed. Our results showed high levels of ALT with liver cells necrosis, increased total 8-isoprostane and nitrotyrosine protein after CC4 administration. NO inhibitors and SNP abrogated these effects. Protein and mRNA levels in CCL-treated mice demonstrated upregulation of TNF-a, iNOS, and COX-2. NO inhibitors with CC4 diminished the expression of these proinflammatory mediators. NF-KB was also upregulated in CC4 treated mice but was reversed in NO inhibitors pretreated mice. CCl4 with SNP showed slightly lower expression of COX-2 when compared with CC14 treated mice but not for TNF-a, iNOS and NF-KB activity. Partial protection of SNP from lipid peroxidation and oxidative stress is due to its scavenging action. We conclude that high level of NO is detrimental in acute liver injury and can he ameliorated by decreasing the NO level with NO inhibitors and NO donor.