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Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 4/2009

01-08-2009 | Original Article

Nitrosative stress, protein tyrosine nitration, PARP activation and NAD depletion in the kidneys of rats after single dose of cyclophosphamide

Authors: Premila Abraham, Suganthy Rabi

Published in: Clinical and Experimental Nephrology | Issue 4/2009

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Abstract

Objectives

Cyclophosphamide (CP) and its structural analogue ifosfamide are highly effective cytostatic drugs. While both cyclophosphamide and ifosfamide have severe urotoxic side effects, only ifosfamide is thought to be nephrotoxic. The nephrotoxicity of CP in generally overlooked because of normal plasma creatinine levels. Therefore, little information is available regarding the pathogenic mechanism of renal damage by CP. In the present study, we investigated the role of nitrosative stress in CP-induced renal damage.

Methods

The experimental rats received a single i.p. of 150 mg/kg body weight CP in saline and were killed 6 h or 16 h later. The control rats received saline. The kidneys were used for histological and biochemical analysis. Nitrotyrosine and poly (ADP-ribose) polymerase (PARP) were localized immunohistochemically as indicators of protein nitration and DNA damage, respectively. Nitrite, NAD and superoxide dismutase (SOD) activity were assayed in the kidney homogenates.

Results

The nitrite level in the kidneys of CP-treated rats was elevated twofold. The kidneys of CP-treated rats stained strongly for nitrotyrosine as well as for PARP. Significant decrease in oxidized NAD levels was also observed in the kidneys of CP-treated rats. The activity of the peroxynitrite sensitive enzyme SOD was significantly reduced in the kidneys of CP-treated rats.

Conclusion

The results of the present study reveal that nitrosative stress may play an important role in CP-induced renal damage. It is suggested that protein nitration, PARP activation and NAD ± depletion may play a critical role in the pathogenesis of cyclophosphamide induced renal damage.
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Metadata
Title
Nitrosative stress, protein tyrosine nitration, PARP activation and NAD depletion in the kidneys of rats after single dose of cyclophosphamide
Authors
Premila Abraham
Suganthy Rabi
Publication date
01-08-2009
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 4/2009
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-009-0160-z

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