Pharmacological Induction of Heme Oxygenase-1 Inhibits iNOS and Oxidative Stress in Renal Ischemia-Reperfusion Injury

Volti, Giovanni Li; Sorrenti, Valeria; Murabito, Paolo; Galvano, Fabio; Veroux, Massimiliano; Gullo, Antonino; Acquaviva, Rosaria; Stacchiotti, Alessandra; Bonomini, Francesca; Vanella, Luca; Giacomo, Claudia Di

doi:10.1016/j.transproceed.2007.09.047

Cited by 57 publications

(41 citation statements)

References 18 publications

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“…The present work, in agreement with previous studies, clearly demonstrated that increased lipid peroxidation, depletion of antioxidant defense mechanisms and the release of pro-inflammatory mediators are greatly responsible for renal injury mediated by ischemia/reperfusion [4,5,22] . In the present study, telmisartan pre-treatment for 7 consecutive days, at a non-hypotensive dose, effectively protected against acute ischemia/reperfusion-induced renal injury as indicated by the significant improvement in the disturbed biochemical parameters and marked amelioration of renal tissue damage observed by light and electron microscopic examinations.…”

Section: Discussionsupporting

confidence: 93%

Nephroprotective Effect of Telmisartan in Rats with Ischemia/Reperfusion Renal Injury

Fouad¹,

Qureshi²,

Al-Sultan³

et al. 2010

Pharmacology

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We investigated the protective effect of telmisartan, an angiotensin II receptor antagonist, against ischemia/reperfusion renal injury in rats. Bilateral ischemia was induced by clamping both renal vascular pedicles for 45 min followed by reperfusion for 3 h. Untreated rats exposed to ischemia/reperfusion showed significant elevations in blood urea nitrogen and serum creatinine levels, renal tissue levels of malondialdehyde, tumor necrosis factor-α and nitric oxide, and caspase-3 activity. This was associated with significant decreases in renal reduced glutathione level, catalase and superoxide dismutase activities. Also, significant increases in serum and renal tissue levels of homocysteine were detected following ischemia/reperfusion. Pre-ischemic treatment with telmisartan (0.3 mg/kg/day, i.p.) for 7 consecutive days significantly attenuated the increases in blood urea nitrogen, serum creatinine, renal malondialdehyde, tumor necrosis factor-α, nitric oxide, caspase-3 activity, and serum and renal homocysteine levels, and significantly restored the renal antioxidant defenses. In addition, light and electron microscopic examinations revealed that telmisartan pre-treatment markedly ameliorated ischemia/reperfusion-induced renal tissue damage. It was concluded that telmisartan, through its antioxidant, anti-inflammatory and antiapoptotic effects, can be considered a potential candidate to protect against acute ischemia/reperfusion renal injury.

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Section: Discussionsupporting

confidence: 93%

Nephroprotective Effect of Telmisartan in Rats with Ischemia/Reperfusion Renal Injury

Fouad¹,

Qureshi²,

Al-Sultan³

et al. 2010

Pharmacology

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“…2,[25][26][27] In this study, pretreatment with fenofibrate alone and in combination with telmisartan for two consecutive weeks effectively protected against Table 2. Renal MDA, GSH, NO, and MPO levels of all experimental groups.…”

Section: Discussionmentioning

confidence: 51%

“…This can be explained by rapid upregulation of mRNA for TNF-a and inducible nitric oxide synthase observed during I/R. 2,27,29 Excess NO exerts toxicological effects such as vasodilation, edema, cytotoxicity, and mediation of cytokine-dependent processes. It reacts with superoxide anion to generate the peroxynitrite radical that causes further cell damage.…”

Section: Discussionmentioning

confidence: 99%

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

et al. 2010

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It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.

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“…These HO-1 enzyme-generated products exhibit free radical scavenging, vasodilating, anti-inflammatory, and anti-apoptotic proprieties. 1,38,39 Indeed, it has been demonstrated that HO-1 induction by pharmacologic preconditioning can prevent cold I/R induced injury in renal graft. 38 Li Volti and his coworkers 39 demonstrated that pharmacologic induction of HO-1 attenuates renal warm I/R injury via inhibiting apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

et al. 2014

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Renal ischemia reperfusion (I/R) injury, which occurs during renal surgery or transplantation, is the major cause of acute renal failure. Trimetazidine (TMZ), an anti-ischemic drug, protects kidney against the deleterious effects of I/R. However its protective mechanism remains unclear. The aim of this study is to examine the relevance of Akt, endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor-1a (HIF-1a) on TMZ induced protection of kidneys against I/R injury. Wistar rats were subjected to 60 min of warm renal ischemia followed by 120 min of reperfusion, or to intraperitoneal injection of TMZ (3 mg/kg) 30 min before ischemia. In sham operated group renal pedicles were only dissected. Compared to I/R, TMZ treatment decreased lactate dehydrogenase (845 ± 13 vs. 1028 ± 30 U/L). In addition, creatinine clearance and sodium reabsorption rates reached 105 ± 12 versus 31 ± 11 mL/min/g kidney weight and 95 ± 1 versus 68 ± 5%, respectively. Besides, we noted a decrease in malondialdehyde concentration (0.33 ± 0.01 vs. 0.59 ± 0.03 nmol/mg of protein) and an increase in glutathione concentration (2.6 ± 0.2 vs. 0.93 ± 0.16 mg GSH/mg of protein), glutathione peroxidase (95 ± 4 vs. 61 ± 3 mg GSH/min/mg of protein), and superoxide dismutase (25 ± 3 vs. 11 ± 2 U/mg of protein) and catalase (91 ± 12 vs. 38 ± 9 mmol/min/mg of protein) activities. Parallely, we noted a significant increase in p-Akt, eNOS, nitrite and nitrate (18 ± 2 vs. 8 ± 0.1 pomL/mg of protein), HIF-1a (333 ± 48 vs. 177 ± 14 mg/mg of protein) and heme oxygenase-1 (HO-1) levels regarding I/R. TMZ treatment improves renal tolerance to warm I/R. Such protection implicates an activation of Akt/eNOS signaling pathway, HIF-1a stabilization and HO-1 activation.

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Pharmacological Induction of Heme Oxygenase-1 Inhibits iNOS and Oxidative Stress in Renal Ischemia-Reperfusion Injury

Cited by 57 publications

References 18 publications

Nephroprotective Effect of Telmisartan in Rats with Ischemia/Reperfusion Renal Injury

Nephroprotective Effect of Telmisartan in Rats with Ischemia/Reperfusion Renal Injury

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

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