Intrarenal Administration of Molsidomine, a Molecule Releasing Nitric Oxide, Reduces Renal Ischemia-Reperfusion Injury in Rats

Abstract

Ischemia reperfusion (I-R)-induced renal damage isreduced by systemic administration of the NOdependent vasodilator molsidomine. The aim of this study was to estimate the effect of direct intrarenal molsidomine administration on renal dysfunction and inflammatory reaction after experimental I-R in rats, in order to assess only renal NO effects and to obviate its systemic hemodynamic action. Ischemia was induced by renal pedicle ligation (60 min) followed by reperfusion and contralateral nephrectomy. Molsidomine (4 mg/kg) was infused into the renal artery 15 min before reperfusion and its effects were compared with those of the NO-independent vasodilator hydralazine (2 mg/kg). Survival rates after 7 days were 100% in the sham-operated group and 75% in the I-R rats. Molsidomine treatment almost completely prevented the I-R-induced renal dysfunction, and survival reached 100%. Molsidomine prevented an I-R-induced increase in superoxide anion and reduced plasma levels of pro-inflammatory cytokines (TNF-a , IL-1b and IFN-c ), whereas it enhanced anti-inflammatory cytokines (IL-6 and IL-10). Inflammatory cell infiltration and celladhesion molecules (ICAM-1, PECAM-1, VCAM-1 and P-selectin) were lower in the molsidomine-treated kidneys than in the untreated animals. All these protective effects were not observed after hydralazine administration. In conclusion, intrarenal administration of molsidomine before reperfusion improved renal function and decreased inflammatory responses after I-R.

Protective effects of molsidomine against doxorubicin-induced renal damage in rats

“…MLS treatment (before and after DOX) ameliorated the histopathological damage caused by DOX; however, treatment with MLS before DOX injection was more effective than treatment with MLS after DOX injection, with respect to protection of tubular structures (p<0.05). Thus, our histopathological results are in agreement both with our biochemical findings and with previously published data [11,12,39,40].…”

“…We focused especially on the antioxidant properties of MLS, rather than the anti-inflammatory effects [9,11]. The analysis of kidney histology used a semiquantitative (vs. quantitative) method involving grading of the anti-inflammatory effects of MLS (Table 3).…”

“…MLS was recently shown to have antioxidant and anti-inflammatory properties [6,8]. Studies demonstrated that the systemic administration of MLS improves survival rates and reduces the renal damage induced by renal ischemia-reperfusion (I-R) in rats, suggesting that it could be a useful agent to protect renal function [9][10][11]. Chander and Chopra [12] recently reported that MLS showed renoprotective effects against ischemia-reperfusion induced renal damage.…”

Activation of Parenchymal CD47 Promotes Renal Ischemia-Reperfusion Injury

“…[8][9][10] Organs subjected to IRI demonstrate suppression of NO, 11 and therapies that supplement NO have been shown to mitigate IRI. [12][13][14][15] In this study, we tested the hypothesis that renal tissue-expressed CD47 promotes IRI. We demonstrate for the first time that TSP1 and CD47 are significantly induced in IRI.…”

The Protective Role of Molsidomine on the Cisplatin-Induced Ototoxicity

“…They suggested that the beneficial effects of MOL may be due to the decreasing of neutrophil infiltration. Rodriguez-Pena et al showed MOL reduced plasma levels of pro-inflammatory cytokines however it increases the levels of antiinflammatory cytokines in rats [26]. Taking into consideration the reduced oxidative damage caused by MOL treatment, all investigators attributed the protective actions of MOL to its antioxidative and anti-inflammatory activities [27].…”