| Nitrosative stress, protein tyrosine nitration, PARP activation and NAD depletion in the kidneys of rats after single dose of cyclophosphamide. | |
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MedLine Citation:
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PMID: 19266253 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Premila Abraham; Suganthy Rabi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-07 |
Journal Detail:
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Title: Clinical and experimental nephrology Volume: 13 ISSN: 1437-7799 ISO Abbreviation: Clin. Exp. Nephrol. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-06 Completed Date: 2009-10-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9709923 Medline TA: Clin Exp Nephrol Country: Japan |
Other Details:
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Languages: eng Pagination: 281-7 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Christian Medical College, Bagayam, Vellore 632002, Tamil Nadu, India. premilaabraham@yahoo.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cyclophosphamide / administration & dosage, toxicity* DNA Damage Down-Regulation Enzyme Activation Immunohistochemistry Injections, Intraperitoneal Kidney / drug effects*, enzymology, pathology Male NAD / metabolism* Nitrates / metabolism Nitrites / metabolism Oxidative Stress / drug effects* Poly(ADP-ribose) Polymerases / metabolism* Rats Rats, Wistar Reactive Nitrogen Species / metabolism* Superoxide Dismutase / metabolism Time Factors Tyrosine / analogs & derivatives*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Nitrates; 0/Nitrites; 0/Reactive Nitrogen Species; 3604-79-3/3-nitrotyrosine; 50-18-0/Cyclophosphamide; 53-84-9/NAD; 55520-40-6/Tyrosine; EC 1.15.1.1/Superoxide Dismutase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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