PJ34, a poly adenosine diphosphate-ribose polymerase inhibitor, attenuates chromate-induced nephrotoxicity

Paola Yam-Canul, Yolanda Irasema Chirino, Dolores Javier Sánchez-González, Claudia María Martínez-Martínez, Cristino Cruz, José Pedraza-Chaverri

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Potassium dichromate (K2Cr2O7)-induced nephrotoxicity is associated with oxidative stress. In addition, the activation of the polyadenosine diphosphate-ribose [poly(ADP-ribose)] polymerase-1 (PARP-1) plays a role in the pathophysiology of some diseases associated with oxidative stress. To clarify the potential role of PARP-1 in this experimental model, N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethyacetamide HCl (PJ34), a highly specific inhibitor of this enzyme, was used. Nephrotoxicity was induced in rats by a single sc injection of K2Cr2O7; studies were performed 2 days later. PJ34 was given intraperitoneally (15 mg/kg) 1 hr before and 1, 5, 24, 26, 31 and 46 hr after K2Cr 2O7 injection. Nephrotoxicity was evaluated by histological analysis and by measuring blood urea nitrogen, serum creatinine, serum glutathione peroxidase activity and urinary excretion of N-acetyl-β-d-glucosaminidase. PARP-1 activation was evaluated by the immunostaining of poly(ADP-ribose). In addition, the following markers of oxidative stress were evaluated: 3-nitrotyrosine, 4-hydroxy-2-nonenal, malondialdehyde and protein carbonyl content. K2Cr2O 7 increased poly(ADP-ribose) content suggesting the PARP-1 activation in this model. PJ34 significantly ameliorated the K2Cr 2O7-induced: (i) nephrotoxicity, (ii) poly(ADP-ribose) accumulation and (iii) oxidative stress. It is concluded that PARP-1 is activated and involved, at least in part, in K2Cr2O 7-induced nephrotoxicity in rats.

Original languageEnglish
Pages (from-to)483-488
Number of pages6
JournalBasic and Clinical Pharmacology and Toxicology
Volume102
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

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