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. 2011 Nov;16(11):1389-96.

The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model

Fatemeh Eshraghi-Jazi  1 , Mehdi Nematbakhsh, Hamid Nasri, Ardeshir Talebi, Maryam Haghighi, Zahra Pezeshki, Tahereh Safari, Farzaneh Ashrafi
Affiliations

The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model

Fatemeh Eshraghi-Jazi et al. J Res Med Sci. 2011 Nov.

Abstract

Background: Cisplatin (CP) as a potential drug for solid tumors produces nephrotoxicity and disturbs endothelial function. CP induced nephrotoxicity may be gender related. Nitric oxide plays a pivotal role in endothelial function and L-arginine as endogenous NO donor promotes endothelial function. The role of L-arginine in CP induced nephrotoxicity model and its gender related was investigated in this study.

Methods: Thirty three Wistar rats were randomly assigned to four groups. The groups 1 (male, n = 6) and 2 (female, n = 11) received a single dose of L-arginine (300 mg/kg, ip), and the day after, they received a single dose of CP (7 mg/kg). The group 3 (male, n = 9) and 4 (female, n = 7) were assigned to the same regimen except for saline instead of L-arginine. All animals were sacrificed one week after CP administration. The levels of blood urea nitrogen (BUN), creatinine and nitrite were measured. The kidneys were also removed for pathological investigations.

Results: Five animals died. All CP treated animals lost weight. The normalized weigh loss was significantly different between male and female in CP+L-arginine treated animals (p < 0.05). BUN and creatinine were increased significantly in male treated with CP and in female treated with CP+L-arginine (p < 0.05). L-arginine reduced BUN in male (not in female) when compared with control groups (p < 0.05). The level of nitrite was increased significantly in L-arginine treated animals. Kidney tissue damage score and normalized kidney weight were greater in females treated with CP+ L-arginine than female received CP alone (p < 0.05).

Conclusions: L-arginine may protect against CP induced nephrotoxicity in male, but it promotes the induced damage in female. The exact mechanism need to be defined.

Keywords: Cisplatin; Gender; L-arginine; Nephrotoxicity; Rat.

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Conflict of interest statement

Conflict of Interests Authors have no conflict of interests.

Figures

Figure 1
Figure 1
The change of normalized weight in four groups of experiment. The weight was normalized with respect to animal weight on the first day of experiment. M, F, LA and CP stand for male, female, L-arginine and cisplatin.
Figure 2
Figure 2
Serum level of blood urea nitrogen (BUN) (A), creatinine (B) and nitrite levels (C) in cisplatin treated groups before and after intervention. M, F, LA and CP stand for male, female, L-arginine and cisplatin.
Figure 3
Figure 3
The pathology damage score (A) and total kidney weight/100 g of body weight (B) in male and female animals treated with cisplatin+L-arginine and cisplatin alone. CP stands for cisplatin.
Figure 4
Figure 4
The pathology images (magnification: 400X) of kidney tissue in four groups of experiment. A: group 1 (male; L-arginine + cisplatin), B: group 2 (female; L-arginine + cisplatin), C: group 3 (male; cisplatin), D: group 4 (female; cisplatin). More tissue damage is shown in B.
See this image and copyright information in PMC

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