title: Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injury.
abstract: The present study examines whether a subchronic probucol treatment of rats offers protection against ischemia-reperfusion (IR) injury in isolated perfused hearts. Sprague-Dawley rats were treated every second day per week with probucol (cumulative dose 120 mg/kg body mass, i.p.) for 4 weeks. In the probucol group, baseline myocardial antioxidant enzyme, glutathione peroxidase (GSHPx), activity was increased (p<0.05), whereas superoxide dismutase (SOD) and catalase (CAT) activities were not changed. Baseline oxidative stress, as indicated by the myocardial lipid peroxidation, was less (p<0.05) in the probucol group. Isolated hearts were subjected to 60 min global I and 20 min R. Recovery of the contractile function in globally ischemic hearts upon reperfusion was 36% in untreated group and 74% in the probucol group. After IR, GSHPx and CAT activities were significantly (p<0.05) higher in the probucol group compared with the control group, whereas SOD did not change. Lipid peroxidation owing to IR was significantly less in the probocol group. These data suggest that probucol treatment improves endogenous antioxidant reserve and protects against increased oxidative stress following IR injury.
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, University of Vermont, Colchester 05446, USA, and Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: Dinender K
authors.initials: DK
authors.lastname: Singla
authors.forename: Kuljeet
authors.initials: K
authors.lastname: Kaur
authors.forename: Anita K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Dhingra
authors.forename: Pawan K
authors.initials: PK
authors.lastname: Singal
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D011341:Probucol