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Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Melatonin attenuates renal ischemia-reperfusion injury in nitric oxide synthase inhibited rats
Esra Deniz1, Neriman Colakoglu, Aysel Sari
1Department of Pharmacology, Faculty of Medicine, Firat University, 23119 Elazig, Turkey.
Abstract:
Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.48+/-0.2mg/l serum) than in the control group (2.69+/-0.2mg/l serum). L-NAME (40 mgkg(-1) for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.
Insights
Melatonin effectively lowers blood pressure and reduces kidney damage from ischemia/reperfusion (I/R) injury, even in rats with inhibited nitric oxide synthase (NOS). This antioxidant effect protects against oxidative stress and structural damage in the kidneys.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Research
Background:
- Melatonin is known to reduce blood pressure and ischemia/reperfusion (I/R) injury.
- Nitric oxide synthase (NOS) inhibition can exacerbate I/R-induced damage.
- Investigating melatonin's protective effects in a model of NOS-inhibited hypertension is crucial.
Purpose of the Study:
- To evaluate the renoprotective effects of melatonin against renal I/R injury in rats treated with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME).
- To assess melatonin's impact on blood pressure and oxidative stress markers in this experimental model.
Main Methods:
- Rats underwent right nephrectomy followed by left renal ischemia/reperfusion (I/R) for 60 minutes and 24 hours of reperfusion.
- Animals were treated with L-NAME to induce hypertension and NOS inhibition.
- Melatonin was administered to assess its effects on blood pressure, malondialdehyde (MDA) levels, and kidney histology.
Main Results:
- Melatonin significantly reduced blood pressure in L-NAME-treated hypertensive rats.
- I/R injury increased malondialdehyde (MDA) levels, a marker of lipid peroxidation.
- L-NAME treatment further elevated MDA levels, but melatonin administration significantly reduced these values, mitigating oxidative stress.
- Melatonin attenuated structural kidney damage induced by I/R, particularly in the presence of L-NAME.
Conclusions:
- Melatonin demonstrates significant blood pressure-lowering effects in NOS-inhibited hypertensive rats.
- Melatonin effectively reduces renal ischemia/reperfusion injury by combating oxidative stress and preserving kidney structure.
- These findings highlight melatonin's therapeutic potential in managing renal injury associated with hypertension and impaired nitric oxide signaling.
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