Effect of methyl-prednisone and cyclosporine on the lipid pattern and polyunsaturated fatty acid biosynthesis in the rat.
The hyperlipidemia posttransplant has been largely attributed to immunosuppressant agents. In the present work we evaluated the effect of oral administration of cyclosporine (5 mg/kg/day) and/or methyl-prednisone (1 mg/kg/day) on lipid composition and polyunsaturated fatty acid biosynthesis in normal adult male rats. The results obtained showed that both agents produced a delay on the growth together with a significant loss of body weight. In liver microsomal fraction from rats treated with methyl-prednisone, a depression in delta 6 and delta 5 desaturation activities, was observed. This effect was corroborated in the fatty acid pattern through the enhancement of linoleic and dihomo-gamma-linolenic acids, and a depression of arachidonic acid. Similar results were noticed in those rats treated with both drugs when compared to the controls. No changes were observed either in the amount of liver microsomal total lipids or in the fatty acid composition of kidney and testis microsomes, as well as in erythrocyte membranes, among the different groups studied. Cyclosporine alone produced a significant depression in plasma triglycerides and showed no modifications in the other lipid parameters studied compared to the controls. Fluorescence anisotropy measured in the different membranes was not modified by the several treatments used. In view of the aforementioned data, it can be stated that methyl-prednisone would be the responsible for many of the lipid disorders that can be observed in posttransplant patients when they are subjected to the combined immunotherapy with cyclosporine.
Gómez Dumm
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Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Raimondi
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C
Touceda
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Fassit
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JC
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011241:Prednisone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005231:Fatty Acids, Unsaturated; D007166:Immunosuppressive Agents; D008055:Lipids; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D011241:Prednisone