TY - JOUR
T1 - PJ34, a poly adenosine diphosphate-ribose polymerase inhibitor, attenuates chromate-induced nephrotoxicity
AU - Yam-Canul, Paola
AU - Chirino, Yolanda Irasema
AU - Sánchez-González, Dolores Javier
AU - Martínez-Martínez, Claudia María
AU - Cruz, Cristino
AU - Pedraza-Chaverri, José
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=42149104494&partnerID=8YFLogxK
U2 - 10.1111/j.1742-7843.2008.00224.x
DO - 10.1111/j.1742-7843.2008.00224.x
M3 - Artículo
C2 - 18331393
SN - 1742-7835
VL - 102
SP - 483
EP - 488
JO - Basic and Clinical Pharmacology and Toxicology
JF - Basic and Clinical Pharmacology and Toxicology
IS - 5
ER -