Nitric oxide release and enhancement of lipid peroxidation in regenerating rat liver.
OBJECTIVE
Clarification of the role of lipid peroxidation in the onset of liver proliferation has been hampered by the fact that both higher and lower lipid peroxidation have been reported after two-thirds partial hepatectomy. Recently, it has been shown that nitric oxide might be involved in the control of early responses after partial hepatectomy. We analysed the possible involvement of nitric oxide production in lipid peroxidation levels during liver regeneration.


METHODS
Sham-operated, hepatectomised and sham and hepatectomised rats pretreated with two inhibitors of oxide nitric synthesis (aminoguanidine or N(G)-monomethyl-L-arginine) were used throughout. Animals were killed at 1, 3, 5 and 15 h after surgery. Cytosolic superoxide dismutase and microsomal-lysosomal catalase activities were measured. Lipid peroxidation levels were measured as thiobarbituric acid-reactive substances and conjugated dienes. Cytosolic nitrate (a stable metabolic product of nitric oxide) was enzymatically determined. Inducible-type nitric oxide synthase (iNOS) was analysed in hepatic cytosol by immunoblotting. DNA synthesis 24 and 48 h after surgery was assessed by [3H]thymidine incorporation.


RESULTS
Increased lipid peroxidation was found in total homogenate, cytosol and microsomes. The hepatic cytosolic content of nitrates increased, reaching the highest values at 5 h posthepatectomy. Aminoguanidine or N(G)-monomethyl-L-arginine pretreatment blocked the rise of nitric oxide production and lipid peroxidation levels and decreased the DNA synthesis. The increase in hepatic iNOS protein expression at 5 h after partial hepatectomy disappeared with aminoguanidine pretreatment.


CONCLUSIONS
Our experiments suggest that nitric oxide plays a role in the proliferation mechanism, although it is responsible, at least in part, for the enhanced lipid peroxidation.
Carnovale
C E
CE
Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Cientificas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas (Universidad Nacional de Rosario), Argentina. ifise1@citynet.net.ar
Scapini
C
C
Alvarez
M L
ML
Favre
C
C
Monti
J
J
Carrillo
M C
MC
D000818:Animals; D002455:Cell Division; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000473:pathology / Q000502:physiology*; D008115:Liver Regeneration; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide