Efficacy and interactions of oxandrolone, halo-fenate and clofibrate in a factorial study on experimental acute nephrotic hyperlipidemia.
Nephrotic mixed hyperlipidemia may be associated with accelerated coronary artery disease. To investigate the response of experimental nephrotic hyperlipidemia to therapy, a 2(4) factorial study of sodium clofibrate and beta-benzalbutyrate, halofenate and oxandrolone (250, 150, 100 and 10 mg/kg/day, respectively) was carried out. Nephrotic syndrome was induced by a single i.p. injection of puromycin aminonucleoside (90 mg/kg) in 80 female white rats of average weight 160 g. Oxandrolone proved to be significantly hypotriglyceridemic in combined therapy (average fall, 38%; P less than .05), and also lowered serum total cholesterol and phospholipid concentrations (23% and 21% falls, P less than .01) and less than .05), due largely to synergistic interactions with clofibrate-like drugs. Hypocholesteremic effects (23 and 22% average falls) were also significant for halofenate (P less than .01) and clofibrate (P less than .05) . Serum triglyceride levels actually rose significantly (P less than .05) with drug combinations containing beta-benzalbutyrate. Clofibrate and its analogs (halofenate and beta-benzalbutyrate) produced significant hepatomegaly (mean responses of +18, +18 and +10%, respectively) whereas oxandrolone produced significant hepatic shrinkage (-10%)(P less than .05). Secondary effects (drug interactions) were also found; hypotriglyceridemic synergism (effects more than additive) occurred between oxandrolone and clofibrate or its analogs (P less than .05), whereas antagonism (effects less than additive) was observed within the clofibrate-like group (P less than .01 or less .05).
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002087:Butyrates / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006016:Glycolates / Q000627:therapeutic use*; D006218:Halofenate / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000033:anatomy & histology; D009404:Nephrotic Syndrome / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D010074:Oxandrolone / Q000627:therapeutic use*; D011692:Puromycin Aminonucleoside; D051381:Rats; D013223:Statistics as Topic
D002087:Butyrates; D006016:Glycolates; D008055:Lipids; D011692:Puromycin Aminonucleoside; D010074:Oxandrolone; D002784:Cholesterol; D002994:Clofibrate; D006218:Halofenate