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. 2000 Mar 21;4(Suppl 1):P49. doi: 10.1186/cc769

Inhibition of inducible nitric oxide synthase (iNOS) reduces multi-organ failure (MOF) in the thioacetamide (TAA) rat model

TM Rahman 1, HJF Hodgson 1
PMCID: PMC3332973

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Introduction

The role of iNOS in MOF has been controversial, studies having presented contradicting results, however, the use of more specific inhibitors of iNOS may provide benefit.

Aim

To examine the effects of iNOS inhibition in our model of TAA induced MOF.

Method

MOF was induced by two intraperitoneal (IP) injections of TAA (500 mg/kg) eight hours apart. Three groups were studied, Group 1 receiving TAA only. Group 2 and 3 followed thr protocol for Group 1, however, Group 2 was pre-treated with the NO precursor L-Arginine (300 mg/kg IP) once daily and Group 3 was pre-treated with NO synthase inhibitor aminoguanidine (100 mg/kg SC) for three days.

Results

See Table. n=10 Mean ± SD.

Histology

The histological sections show markedly less organ damage in the aminoguanidine group (Group 3).

Conclusion

Inhibition of iNOS using aminoguanidine significantly improves the incidence of MOF and mortality in the TAA model of MOF.

Table.

Groups AST (iu/l) Creatinine (umol/l) Lactate mmol/l Survival %




Time (h) 24 48 24 48 24 48 96
Control   34± 10   41± 12   43± 13   51± 10 1.5± 0.3 1.4± 0.2 100
TAA 1653± 164 4045± 247 167± 22 231± 37 3.9± 0.9 6.2± 0.7 25
TAA + L-ARG 2177± 231 4475± 240 187± 14 271± 27 4.2± 0.5 7.3± 0.7 10
TAA + AMG 346± 50 1090± 188 87± 21 112± 23 2.1± 0.2 3.4± 0.3 90

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