Exogenous and Endogenous Nitric Oxide but Not iNOS Inhibition Improves Function and Survival of Ischemically Injured Livers
The role of nitric oxide (NO) in liver ischemia/reperfusion I/R) injury remains controversial and few works have shed more information regarding the effect of exogenous (EX) and/or endogenous NO (EN) under conditions of I/R of the liver. We investigated the role of exogenous and endogenous NO and in...
Gespeichert in:
Veröffentlicht in: | Journal of investigative surgery 2001, Vol.14 (5), p.267-273 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | The role of nitric oxide (NO) in liver ischemia/reperfusion I/R) injury remains controversial and few works have shed more information regarding the effect of exogenous (EX) and/or endogenous NO (EN) under conditions of I/R of the liver. We investigated the role of exogenous and endogenous NO and inducible nitric oxide synthase (iNOS) inhibition in liver function, neutrophil infiltration, and animal survival after liver I/R. Sprague-Dawley rats were subjected to total hepatic ischemia for 90 min using an extracorporeal porto-systemic shunt. The animals were divided into five groups, including the sham porto-systemic shunt with no ischemia, the control ischemic group, the L-arginine-treated group, the sodium nitroprusside (SNP or NaNP)-treated group, and the L- N 6 -(1-iminoethyl) lysine hydrochloride (L-NIL) (selective iNOS inhibitor)-treated group. The animal survival was followed for 7 days. Liver injury tests, tissue myeloperoxidase (MPO), and histology were analyzed at 6 h postreperfusion. L-Arginine- and sodium nitroprusside-treated groups demonstrated significant improvement in 7 days survival in comparison to the control (20%) ( p < .05). The best overall survival was obtained with SNP (70%), followed by survival in the L-arginine treated group (60%). The iNOS inhibitor group (40%) did not show any statistical significance when compared to the control group ( p > .05). Liver injury tests and histology scores in the SNP- and L-arginine-treated groups showed significant improvement when compared to the control group ( p < .01 and p < .05, respectively). The iNOS group demonstrated only a slight improvement in these parameters. The liver MPO (as a measurement of neutrophil migration into the liver parenchyma) was significantly decreased only in the SNP and L-arginine groups ( p < .05) but not in the iNOS group ( p > .5). We conclude that NO exogenous donors and substrates for the endogenous pathway are beneficial for the liver after severe I/R and could be important therapeutic targets to prevent damage following this phenomenon. |
---|---|
ISSN: | 0894-1939 1521-0553 |
DOI: | 10.1080/089419301753170048 |