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Updated: Apr 20, 2026
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Evaluation of l-arginine on kidney function and vascular reactivity following ischemic injury in rats: protective
Amira M Senbel1, Amal G Omar1, Lobna M Abdel-Moneim2
1Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Background:
There is an interaction between many cell types involved in the pathophysiology of ischemic acute renal failure. Nitric oxide (NO) precursors, especially l-arginine, may have protective effects on tissue ischemia/reperfusion injury (IRI); however, their molecular mechanisms are unclear. In the present study, the interaction between l-arginine, cyclo-oxygenase (COX)-2 and reactive oxygen species (ROS) in the pathogenesis of ischemic acute renal failure was investigated.
Methods:
Ischemia/reperfusion injury model in rats was used and various biochemical parameters examined. The rat isolated aortic rings served as model for hypoxia/reoxygenation where endothelium dependent and independent relaxations were exerted.
Results:
Pre-treatment of rats subjected to IRI with l-arginine (125mg/kg) significantly reduced kidney MDA levels, elevated kidney SOD activity, GSH level and total NO levels at 24 and 48h after reperfusion. Kidney COX-2 level was only different in the l-arginine-treated group 48h after reperfusion compared to the IRI group. Pre-treatment with l-arginine (10(-2)M) alone or in combination with celecoxib significantly potentiated the acetylcholine (Ach)-induced relaxations in control and hypoxic rings. The effect of the combination was synergistic only in hypoxic rings. Addition of ascorbic acid to the celecoxib-arginine combination did not produce further potentiation. Sodium nitroprusside-induced relaxations in control and hypoxic rings were potentiated by l-arginine or celecoxib-arginine combination but not by ascorbic acid.
Conclusions:
The protective effect of l-arginine may result from the interaction between NO and ROS and increased NO bioavailability. The protective effects of combined celecoxib and l-arginine against IRI could be attributed to their antioxidant activity which exceeded that of ascorbic acid.
Insights
L-arginine protects against kidney injury by increasing nitric oxide (NO) bioavailability and interacting with reactive oxygen species (ROS). Combined with celecoxib, it shows enhanced antioxidant activity against ischemia/reperfusion injury (IRI).
Area of Science:
- Nephrology
- Cardiovascular Research
- Biochemistry
Background:
- Ischemic acute renal failure involves complex cell interactions.
- Nitric oxide (NO) precursors like l-arginine may offer protection against ischemia/reperfusion injury (IRI).
- The precise molecular mechanisms of l-arginine's protective effects in IRI remain unclear.
Purpose of the Study:
- To investigate the interaction between l-arginine, cyclo-oxygenase (COX)-2, and reactive oxygen species (ROS).
- To elucidate the role of these factors in the pathogenesis of ischemic acute renal failure.
Main Methods:
- Utilized an ischemia/reperfusion injury (IRI) model in rats.
- Examined various biochemical parameters, including kidney MDA, SOD, GSH, and total NO levels.
- Employed isolated rat aortic rings to model hypoxia/reoxygenation, assessing endothelium-dependent and independent relaxations.
Main Results:
- L-arginine pre-treatment significantly reduced kidney MDA levels and increased SOD activity, GSH, and total NO levels post-IRI.
- Kidney COX-2 levels were altered in the l-arginine-treated group 48 hours post-reperfusion.
- L-arginine, alone or with celecoxib, potentiated acetylcholine-induced relaxations, with synergistic effects observed in hypoxic rings.
Conclusions:
- L-arginine's protective effect in IRI likely stems from NO-ROS interactions and enhanced NO bioavailability.
- Combined celecoxib and l-arginine demonstrated superior antioxidant activity compared to ascorbic acid in protecting against IRI.
