Modulation of adriamycin-induced changes in serum free fatty acids, albumin and cardiac oxidative stress.
Adriamycin-induced cardiomyopathic changes are prevented by combination therapy with probucol. These beneficial effects are suggested to be due to a combination of antioxidant as well as lipid-lowering effects of probucol. In the present study, we compared the effects of probucol (PROB) with that of lovastatin (LOV), a lipid-lowering drug, and trolox (TRO), an antioxidant, on adriamycin (ADR)-induced subchronic in vivo changes in serum free fatty acids (FFA), serum albumin and myocardial reduced (GSH) and oxidized (GSSG) glutathione in rats. ADR caused a significant increase in FFA, decrease in albumin, and an increase in FFA/albumin. PROB and LOV modulated the increases in FFA and FFA/albumin, while TRO was without any effect. ADR reduced myocardial GSH, increased GSSG and decreased GSH/GSSG. Only PROB caused significant improvement in GSH and normalized GSSG levels. It is suggested that these modulatory effects of probucol may also contribute in the beneficial effects of this drug against adriamycin-induced cardiomyopathy and congestive heart failure.
Iliskovic
N
N
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Li
T
T
Khaper
N
N
Palace
V
V
Singal
P K
PK
D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D004317:Doxorubicin / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D012709:Serum Albumin; D004317:Doxorubicin; D005978:Glutathione