Clopidogrel protects from cell apoptosis and oxidative damage in a mouse model of renal ischaemia-reperfusion injury.
J Pathol
; 225(2): 265-75, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21630270
ABSTRACT
Renal ischaemia-reperfusion injury (IRI) is consecutive to tissue oxidative damage and cell apoptosis that lead to acute renal failure (ARF) in renal allografts. The aim of this study was to investigate the beneficial effects of a pretreatment by clopidogrel on renal IRI in mice. IRI was induced by bilateral renal ischaemia for 45 min followed by reperfusion. Sixty-two healthy male BALB/c mice were randomly assigned to one of the following groups PBS + ischaemia-reperfusion (IR); clopidogrel + IR; PBS + sham IR; clopidogrel + sham IR. Clopidogrel (25 mg/kg) or PBS was administered per os to the animals via a gastric cannula 24 h before operation. All mice were given a single dose of clopidogrel or PBS. Renal function histological damage, renal cell apoptosis, renal antioxidant activities, and CD41 expression were determined 24 h after reperfusion. The survival rates were evaluated over 7 days. Animals pretreated with clopidogrel had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores, and improved survival rates following IR. Renal cell apoptosis induced by IR was decreased in kidneys of mice pretreated by clopidogrel, with an increase in Bcl-2 and Bcl-xL expression and a decrease in caspase-3, caspase-8, and Bax expression. Renal reduced glutathione, superoxide dismutase, and catalase activities were unmodified by the pretreatment with clopidogrel. However, clopidogrel resulted in an increased total antioxidant capacity of the kidney. Furthermore, pretreatment by clopidogrel decreased the number of CD41-positive cells. Thus, clopidogrel exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis as a consequence of improved renal antioxidant capacity and could be tried as a novel therapeutic tool in renal IRI.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ticlopidina
/
Traumatismo por Reperfusão
/
Apoptose
/
Estresse Oxidativo
/
Antagonistas do Receptor Purinérgico P2Y
/
Rim
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pathol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
França