Protective Effects of L‐Arginine against Cisplatin‐Induced Renal Oxidative Stress and Toxicity: Role of Nitric Oxide

Abstract

Nephrotoxicity is a dose-limiting factor in clinical use of cisplatin. The changes in renal haemodynamics were suggested to play a role in cisplatin-induced nephrotoxicity. The aim of the present study was to investigate the effect of modulation of nitric oxide on the severity of cisplatin-induced nephrotoxicity using an experimental rat model. A nitric oxide precursor, L-arginine and an inhibitor of nitric oxide synthase, L-NAME were used. After six days of cisplatin injection, acute nephrotoxicity was demonstrated by a marked increase in serum creatinine and blood urea nitrogen. Histological examination of the kidneys confirmed the occurrence of renal damage. Moreover, cisplatin induced an increase in the level of lipid peroxides and oxidized glutathione and a depletion of reduced glutathione. The activities of the antioxidant enzymes glutathione peroxidase and superoxide dismutase were also lowered. Besides, there was a reduction in the kidney total nitrate/nitrite levels. L-arginine significantly attenuated the oxidative stress and nephrotoxic effect of cisplatin. On the other hand, L-NAME was found to aggravate cisplatin nephrotoxicity. In conclusion, the decrease in the kidney nitric oxide level contributes, at least in part, in the mechanism underlying the nephrotoxicity of cisplatin. Furthermore, L-arginine shows nephroprotective effects and might be useful in improving the therapeutic index of cisplatin

Protective Effect of Lactoferrin on Cisplatin-Induced Nephrotoxicity in Rats

“…Hayashida et al [11] reported that bLf causes a nitric oxide (NO)-dependent relaxation of smooth muscle in the rat's aorta, suggesting that bLf can affect the blood circulation in individual organs. The involvement of NO in the renoprotective effect in cisplatin-injected rats was supported by a treatment with L-arginine resulting in NO modulation [22]. Hydration with saline also has a renoprotective effect on cisplatin-injected rats [23].…”

Protective Role of Aerobic Exercise Against Cisplatin-Induced Nephrotoxicity in Rats

“…It is reported that appropriate exercise increases antioxidant enzymes (37) and decreases MDA level (20,38). Furthermore, treatment with antioxidants reduces CP-induced nephrotoxicity (13,14,27,30,36,39). It seems that the positive effect of aerobic exercise on antioxidant defense system can reduce CP-induced nephrotoxicity.…”

Protective Effects of Vitamin C on Cisplatin-Induced Renal Damage: A Light and Electron Microscopic Study

“…These data are corroborated by previous studies. [7,9,19,28] Blisard et al noted that the cells in the interstitial tissue are both mononuclear and polymorphonuclear cells, [8] while el-Shazly et al [9] and Guinee et al [28] observed that these cells are lymphocytes.…”

“…[1] The exact cellular mechanism of cisplatin-induced nephrotoxicity is insufficiently known. [6,7] Thus, the effect of cisplatin has been studied in animals with the aim of understanding mechanisms of toxicity. [5,8,9] The mechanism by which cisplatin induces renal injury is not well understood.…”