Endogenous nitric oxide and exogenous nitric oxide supplementation in hepatic ischemia-reperfusion injury in the rat.
BACKGROUND
Although nitric oxide (NO) is thought to be beneficial in hepatic ischemia-reperfusion (I/R), the mechanisms for this effect are not well established.


METHODS
To investigate the effects of endogenous NO and exogenous NO supplementation on hepatic I/R injury and their pathogenic mechanisms, serum ALT and hyaluronic acid (endothelial cell damage), and hepatic malondialdehyde and H2O2 (oxidative stress), myeloperoxidase activity (leukocyte accumulation), and endothelin (vasoconstrictor peptide opposite to NO) were determined at different reperfusion periods in untreated rats and rats receiving L-NAME, L-NAME+L-arginine, and spermine NONOate (exogenous NO donor).


RESULTS
After reperfusion every parameter increased in untreated animals. Endogenous NO synthesis inhibition by L-NAME increased hepatocyte and endothelial damage as compared to untreated rats, which was reverted and even improved by the addition of L-arginine. Spermine NONOate also improved this damage. However, different mechanisms account for the beneficial effect of endogenous and exogenous NO. Oxidative stress decreased by both L-NAME and L-NAME+L-arginine, but remained unmodified by spermine NONOate. Myeloperoxidase increased by L-NAME and this effect was reverted by the addition of L-arginine, whereas no change was observed with spermine NONOate. Endothelin levels were not modified by L-NAME and L-NAME+L-arginine, but decreased with spermine NONOate.


CONCLUSIONS
These results suggest that, although both endogenous and exogenous NO exert a protective role in experimental hepatic I/R injury, the mechanisms of the beneficial effect of the two sources of NO are different.
Peralta
C
C
Department of Medical Bioanalysis, IIBB-CSIC, Hospital Clínic, University of Barcelona, Villarroel, Spain.
Rull
R
R
Rimola
A
A
Deulofeu
R
R
Roselló-Catafau
J
J
Gelpí
E
E
Rodés
J
J
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019587:Dietary Supplements; D016232:Endothelins / Q000378:metabolism; D006820:Hyaluronic Acid / Q000032:analysis; D008099:Liver / Q000098:blood supply* / Q000737:chemistry; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology*; D018709:Statistics, Nonparametric; D013481:Superoxides / Q000032:analysis
D016232:Endothelins; D013481:Superoxides; D009569:Nitric Oxide; D008315:Malondialdehyde; D006820:Hyaluronic Acid; D009195:Peroxidase; D000410:Alanine Transaminase