Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress in renal ischemia-reperfusion injury

被引：73

作者：

Volti, G. Li ^{[1
]}

Sorrenti, V. ^{[1
]}

Murabito, P. ^{[1
]}

Galvano, F. ^{[1
]}

Veroux, M. ^{[1
]}

Gullo, A. ^{[1
]}

Acquaviva, R. ^{[1
]}

Stacchiotti, A. ^{[1
]}

Bonomini, F. ^{[1
]}

Vanella, L. ^{[1
]}

Di Giacomo, C. ^{[1
]}

机构：

[1] Univ Catania, Dept Biol Chem, Catania, Italy

来源：

TRANSPLANTATION PROCEEDINGS | 2007年 / 39卷 / 10期

关键词：

D O I：

10.1016/j.transproceed.2007.09.047

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：2986 / 2991

页数：6

共 20 条

[1] THE PHYSIOLOGICAL SIGNIFICANCE OF HEME OXYGENASE [J].