The exact functional role of nitric oxide
(NO) in liver injury is currently a source of controversy.
NO is enzymatically synthesized by nitric oxide
synthase (NOS). In this study, we assessed the role of
inducible NOS (iNOS) in carbon tetrachloride (CCl4)-
induced acute liver injury using inhibitors of iNOS, and
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hemisulfate [SMT] and l-N6-(1-iminoethyl)-lysine [LNIL])
and an NO donor (Sodium Nitroprusside [SNP]).
Blood and liver tissues were collected for analysis.
Immunohistochemistry (IHC), serum alanine
aminotransferase (ALT), serum total 8-isoprostane
analysis, RT-PCR, Western Blotting (WB) and EMSA
were done. Our results showed increased levels of ALT,
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these effects but the effect was more pronounced with
SMT and L-NIL. RT-PCR, WB and IHC in CCl4–treated
mice demonstrated upregulation of TNF-a, iNOS, and
COX-2. The administration of iNOS inhibitors with
CCl4 diminished the expression of these
proinflammatory mediators. NF-kB was also
upregulated in CCl4-treated mice and was reversed in
mice pretreated with iNOS inhibitors. SNP pretreated
mice also showed a lower expression of COX-2 when
compared with CCl4 treated mice but TNF-a, iNOS and NF-kB activity were unaffected. We propose that a high
level of nitric oxide is associated with CCl4-induced
acute liver injury and the liver injury can be ameliorated
by decreasing the NO level with iNOS inhibitors and an NO donor with the former more effective in reducing
CCl4-induced liver injury