Differences in iNOS inhibition in an animal model of acute hepatic and multi-organ failure

Introduction

iNOS inhibition in AHF is controversial, fuelled by conflicting results from studies using varieties of pharmacological agents, animal models and temporal protocols.

Methods

We have previously described a robust model of acute hepatic and multi-organ failure in the Wistar rat. AHF was induced by two i.p. injections (500 mg/kg, 8 hours apart) of thioacetamide (TAA). Six groups were studied (n = 5). Group 1 received TAA alone. Groups 2, 3 & 4 followed protocol for Group 1, however, Groups 2 & 3 were pre-treated and Groups 4 & 5 post-TAA treated with iNOS inhibitors AMG (100 mg/kg s.c.) and L-NAME (100 mg/kg s.c.) for 5 days.

Results

See Table

Table 1

Conclusion

AMG is a more selective iNOS inhibitor, significantly reducing parameters of AHF compared L-NAME. Beneficial effects are, however, negated if iNOS inhibitors are administered after TAA, exacerbating hepatic injury, increasing mortality, and thus demonstrating temporal constraints.