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

Eshraghi-Jazi F, Nematbakhsh M, Nasri H, Talebi A, Haghighi M, Pezeshki Z, Safari T, Ashrafi F - J Res Med Sci (2011)

Bottom Line: 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).

Affiliation: Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

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.

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.
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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.

Mentions: BUN and Cr were increased in all CP treated groups, but it was only statistically significant in male treated with CP and in female treated with CP+L-arginine (p < 0.05). L-arginine attenuates the levels of BUN and Cr in male but not in female when compared with control groups (the BUN reduction was significantly different, p < 0.05). The nitrite level increased in L-arginine treated animals (male, p < 0.1; female, p < 0.05), but at the end of the experiment, a significant difference in nitrite level was only detected between females groups (p < 0.05) (Figure 2). On the whole, these findings indicated that L-arginine provides different pattern of effect on BUN, Cr and nitrite levels in CP-induced nephrotoxicity model in male and female rats.

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

Eshraghi-Jazi F, Nematbakhsh M, Nasri H, Talebi A, Haghighi M, Pezeshki Z, Safari T, Ashrafi F - J Res Med Sci (2011)

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.
© Copyright Policy
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.
Mentions: BUN and Cr were increased in all CP treated groups, but it was only statistically significant in male treated with CP and in female treated with CP+L-arginine (p < 0.05). L-arginine attenuates the levels of BUN and Cr in male but not in female when compared with control groups (the BUN reduction was significantly different, p < 0.05). The nitrite level increased in L-arginine treated animals (male, p < 0.1; female, p < 0.05), but at the end of the experiment, a significant difference in nitrite level was only detected between females groups (p < 0.05) (Figure 2). On the whole, these findings indicated that L-arginine provides different pattern of effect on BUN, Cr and nitrite levels in CP-induced nephrotoxicity model in male and female rats.

Bottom Line: 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).

Affiliation: Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

ABSTRACT

Background:

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.

View Similar Images In: Results  - Collection
View Article: Pubmed Central -  PubMed
Show All Figures - Show MeSH
getmorefigures.php?pmc=3430054&rFormat=json&query=null&req=5