title: Clopidogrel protects from cell apoptosis and oxidative damage in a mouse model of renal ischaemia-reperfusion injury.
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.
authors.affiliation: Université Paris Descartes, Faculté de Médecine, EA 1833, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Honglin
authors.initials: H
authors.lastname: Hu
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.forename: Christiane
authors.initials: C
authors.lastname: Chéreau
authors.forename: Niloufar
authors.initials: N
authors.lastname: Kavian
authors.forename: Wioleta
authors.initials: W
authors.lastname: Marut
authors.forename: Camille
authors.initials: C
authors.lastname: Gobeaux
authors.forename: Didier
authors.initials: D
authors.lastname: Borderie
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Dinh-Xuan
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.forename: Carole
authors.initials: C
authors.lastname: Nicco
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077144:Clopidogrel; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine