Counteraction of oxalate induced nitrosative stress by supplementation of l-arginine, a potent antilithic agent

Abstract

Background: Our understanding of nitrosative stress in the process of urolithiasis is far from complete. Earlier studies carried out in our laboratory demonstrate the presence of nitrated THP in stone formers, l-arginine (l-arg) a precursor of nitric oxide (NO), attenuates the endothelial dysfunction caused by reactive nitrogen species. We investigated the role of l-arg in ethylene glycol (EG)-induced urolithic rat model and observed its antilithic and antioxidative properties.

Methods: Hyperoxaluria was induced using 0.75% EG in drinking water. l-arg [1.25 g/kg body weight] was given orally for a period of 28 days.

Results: EG-treated rats showed significant loss in body weight and increase in the activities of oxalate synthesizing enzymes such as glycollic acid oxidase in liver. Lactate dehydrogenase activity in liver and kidney was increased. The activity of the free radical producing enzyme xanthine oxidase, tissue oxalate and calcium levels were significantly increased in EG-treated rats. Depletion in the antioxidant enzymes, membrane bound ATPases and thiol status was observed in these rats. l-arg co-supplementation to EG-treated rats maintained the activities of the oxalate synthesizing enzymes and free radical producing enzymes with in the normal range. Tissue oxalate and calcium levels were also maintained near normal in l-arg treated hyperoxaluric rats. l-arg, by its cytoprotective effect, maintained the thiol status, thereby preserving the activities of the membrane bound ATPases and preventing proteinuria and subsequent weight loss in EG-treated rats.

Conclusion: l-arg feeding prevents the retention of calcium oxalate crystals in hyperoxaluric rats by way of protecting the renal cells from oxidative injury and also by providing a second line of defense through the normalization of the oxalate metabolism. It reduces the risk of stone formation, by curtailing free radicals and hyperoxaluria as both of them have to work in close association to form stones.