Pharmacological induction of heme-oxygenase-1 inhibits iNOS and oxidative stress in renal ischemia-reperfusion injury
Articolo
Data di Pubblicazione:
2007
Citazione:
Pharmacological induction of heme-oxygenase-1 inhibits iNOS and oxidative stress in renal ischemia-reperfusion injury / L. Volti G, V. Sorrenti, P. Murabito, F. Galvano, M. Veroux, A. Gullo, R. Acquaviva, A. Stacchiotti, F. Bonomini, L. Vanella, D. Giacomo C. - In: TRANSPLANTATION PROCEEDINGS. - ISSN 0041-1345. - 39:10(2007), pp. 2986-2991.
Abstract:
Nitric oxide (NO), produced by nitric oxide synthase, is implicated in the pathophysiology of renal ischemia/reperfusion (I/R) injury. This study sought to elucidate the impact of pharmacological induction of heme oxygenase-1 (HO-1) on renal I/R injury. Rats were subjected to 45 minutes of renal ischemia followed by various times of reperfusion (30 minutes, 1 hour, or 3 hours). Plasma from sacrificed rats was obtained, and the kidneys processed for the expression of iNOS, cleaved caspase-3, p38MAPK and for immunohistochemical analysis. Furthermore, we determined renal and plasma levels of lipid hydroperoxides, total thiol groups, and plasmatic NO2-/NO3- formation. Our results showed a time-dependent increase in iNOS expression, which was also confirmed by increased plasma formation of NO2-/NO3- Interestingly, this effect was reversed by pretreatment (12 hours) with SnCl2, a potent and specific inducer of renal HO-1 expression and activity, or by intraperitoneal injection of biliverdin (10 mg/kg). Furthermore, we observed a concomitant reduction in plasma and renal LOOH formation, a normalization of renal total thiol content, a reduction of caspase-3-mediated apoptosis, and a significant increase in p38MAPK phosphoration. Taken together, these results suggested that HO-1 and its byproduct biliverdin play major roles in the pathophysiological. cascade leading to renal I/R injury.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Protein-kinase pathway; carbon-monoxide; risk-factors; rat-kidney; failure; expression
Elenco autori:
L. Volti G, V. Sorrenti, P. Murabito, F. Galvano, M. Veroux, A. Gullo, R. Acquaviva, A. Stacchiotti, F. Bonomini, L. Vanella, D. Giacomo C
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