Inhibiting inducible nitric oxide synthase with rutin reduces renal ischemia/reperfusion injury

Abstract

Background: Nitric oxide (NO) seems to play an important role during renal ischemia/reperfusion (I/R) injury. We investigated whether rutin inhibits inducible nitric oxide synthase (iNOS) and reduces 3-nitrotyrosine (3-NT) formation in the kidneys of rats during I/R. Methods:Wistar albino rats were nephrectomized unilaterally and, 2 weeks later, subjected to 45 minutes of left renal pedicle occlusion followed by 3 hours of reperfusion. We intraperitoneally administered L-N6-(1-iminoethyl)lysine (L-NIL; 3 mg/kg) for 30 minutes or rutin (1 g/kg) for 60 minutes before I/R. After reperfusion, kidney samples were taken for immunohistochemical analysis of iNOS and 3-NT. We measured plasma nitrite/nitrate and cyclic guanosine monophosphate (cGMP) to evaluate NO levels.Results: Ischemia/reperfusion caused plasma cGMP to increase significantly. Similarly, plasma nitrite/nitrate was elevated in the I/R group compared with the control group. Histochemical staining was positive for iNOS and 3-NT in the I/R group. Pretreatment with L-NIL or rutin significantly mitigated the elevation of plasma cGMP and nitrite/nitrate. These changes in biochemical parameters were also associated with changes in immunohistochemical appearance. Pretreatment with L-NIL or rutin significantly decreased the incidence and severity of iNOS and 3-NT formation in the kidney tissues. Conclusion:Our findings suggest that high activity of iNOS causes renal I/R injury, and that rutin exerts protective effects, probably by inhibiting iNOS.Contexte : L'oxyde nitrique (NO) semble jouer un rôle important durant la lésion d'ischémie/reperfusion (I/R) rénale. Nous avons vérifié si la rutine inhibe l'oxyde nitrique synthase inductible (iNOS) et réduit la formation de 3-nitrotyrosine (3-NT) dans les reins de rats durant l'I/R. Méthodes :Des rats albinos Wistar ont subi une néphrectomie unilatérale avant d'être soumis 2 semaines plus tard à une occlusion du pédicule rénal gauche d'une durée de 45 minutes, suivie de 3 heures de reperfusion. Nous avons administré de la L-N6-(1-iminoéthyl)lysine (L-NIL; 3 mg/kg) par voie intrapéritonéale pendant 30 minutes ou de la rutine (1 g/kg) pendant 60 minutes avant l'I/R. Après la reperfusion, des échantillons de tissu rénal ont été prélevés pour analyse immunohistochi mique de l'iNOS et de la 3-NT. Nous avons mesuré les taux plasmatiques de nitrite/nitrate et de guanosine monophosphate cyclique (cGMP) pour évaluer les taux de NO.

Bioavailability of phenolic compounds and redox state of murine liver and kidney as sex-dependent responses to phytoextracts

“…On the other hand, nitrosative stress is a deleterious condition for cells and tissues, and its modulation has been proposed in prevention of chronic diseases (37) . In the present work, extracts maintained normal levels in liver and kidney of nitrites (nitrosative markers), or even reduced them (38) . About this, antioxidant phytochemicals cause down-regulation of inducible nitric oxide synthase, which is the precursor of these markers (38) .…”

“…In the present work, extracts maintained normal levels in liver and kidney of nitrites (nitrosative markers), or even reduced them (38) . About this, antioxidant phytochemicals cause down-regulation of inducible nitric oxide synthase, which is the precursor of these markers (38) . Furthermore, nitrite decrease was related to modulation of lipid peroxidation in males, thus indicating their involvement in tissue stress, with this relation being proposed (39,40) .…”

Cerebroprotective activity of Pentapetes phoenicea on global cerebral ischemia in rats

“…Activated endothelial cells in all segments of the microcirculation produce more oxygen radicals. [10]…”

“…Juice is also applied to inflammatory glands. [10] It also alleviates psychopathy and central nervous system ailments. The presence of rutin in the hydroalcoholic extract of P. phoenicea plant was confirmed with the help of high performance thin layer chromatography studies.…”

You-gui Pill ameliorates renal tubulointerstitial fibrosis via inhibition of TGF-β/Smad signaling pathway

“…Cuscuta chinensis Lam. and its extracts, such as rutin, quercerin and cinnamic acid have been reported to attenuate renal damage induced by ischemia/reperfusion injury, experimental diabetic nephropathy and renal fibrosis in rats with UUO (Donnapee et al, 2014;Hao et al, 2012;Korkmaz and Kolankaya, 2013;Yan et al, 2014). Therefore, it is reasonable to assume that the improving effect of YGW on the TIF in our research may be caused via a synergistic effect derived from these herbs.…”