Drug Discov Ther. 2011;5(1):32-40. (DOI: 10.5582/ddt.v5.1.32)

A comparative study of protective mechanisms of glycine and L-arginine against cisplatin-induced nephrotoxicity in rat renal cortical slices.

Mahran YFK, Khalifa AE, El-Demerdash E


Amino acids exert nephroprotective effects in various forms of acute renal injury depending on their renal hemodynamic effects. The present study was designed to elucidate and compare the role of non hemodynamic mechanisms in protective actions afforded by glycine and L-arginine against cisplatin (CDDP)-induced nephrotoxicity using rat renal cortical slices (RCS). We have investigated the possible modulatory effect of glycine and L-arginine on oxidative stress and necrosis induced by CDDP as well as on CDDP uptake by kidney. After 4 h of incubation with 2 mM CDDP, nephrotoxicity was demonstrated by significant increased lactate dehydrogenase leakage, decreased ability of the slices to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, increased lipid peroxides and depleted reduced glutathione. Also, CDDP significantly inhibited pyruvate-stimulated gluconeogenesis. Histopathological examination of RCS confirmed the occurrence of tubular coagulative necrosis in cortex and corticomedullary regions. Preincubation of RCS with 1 mM glycine or L-arginine 1 h before CDDP addition significantly attenuated the oxidative stress and tubular necrotic effects of CDDP. L-Arginine showed greater antioxidant properties while glycine showed a greater antinecrotic effect. Moreover, the nephroprotective effect was mediated through lowering the platinum uptake by RCS. However, they could not counteract the inhibition of gluconeogenesis induced by CDDP. In conclusion, the present study sheds light on the mechanisms involved in glycine and L-arginine nephroprotection.

KEYWORDS: Cisplatin (CDDP), nephrotoxicity, glycine, L-arginine, renal cortical slices (RCS), lactate dehydrogenase (LDH)

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