Lovastatin is hypertriglyceridemic in Syrian golden hamsters.
The effects of a potent HMG CoA reductase inhibitor, lovastatin, was studied in male Syrian Golden hamsters. Lovastatin (0.1% in food for 6 days) increased hamster serum triglycerides by 12-fold with 2.4-fold increase in serum cholesterol. On continuous treatment serum triglyceride and cholesterol levels gradually decreased to below control values by 12-18 days. When hamsters were fed a mixture of lovastatin and Na-mevalonate no increase in serum triglyceride was observed. [14C]Cholesterol synthesis was increased by 266-fold in livers of hamsters fed lovastatin for 6 days. The increased synthesis of endogenous mevalonate metabolites may be a reason for the decrease in triglyceride levels after 6 days in our studies. The present study suggests that a mevalonate metabolite(s) is necessary for normal triglyceride metabolism in hamsters.
Amin
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Department of Pharmacology, Rorer Central Research, Horsham, PA 19044.
Gustafson
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Perrone
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MH
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D006224:Cricetinae / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015228:Hypertriglyceridemia / Q000139:chemically induced*; D008099:Liver / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology*; D008647:Mesocricetus / Q000502:physiology*; D008798:Mevalonic Acid / Q000494:pharmacology; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D008148:Lovastatin; D008798:Mevalonic Acid