Effect of methyl-prednisone and cyclosporine on the lipid pattern and polyunsaturated fatty acid biosynthesis in the rat.

I N Gómez Dumm, C Raimondi, L Touceda, J C Fassit
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Abstract

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.

甲基强的松和环孢素对大鼠脂质模式和多不饱和脂肪酸生物合成的影响。
移植后高脂血症很大程度上归因于免疫抑制剂。在本工作中,我们评估了口服环孢素(5mg /kg/天)和/或甲基强的松(1mg /kg/天)对正常成年雄性大鼠脂质组成和多不饱和脂肪酸生物合成的影响。结果表明,这两种药物都能延缓生长,同时显著减轻体重。在甲基强的松处理的大鼠肝微粒体部分中,观察到δ 6和δ 5去饱和活性的降低。这种效应在脂肪酸模式中得到证实,通过增强亚油酸和二同γ -亚麻酸,抑制花生四烯酸。与对照组相比,接受两种药物治疗的大鼠也出现了类似的结果。在不同的研究组中,肝脏微粒体总脂质的数量、肾脏和睾丸微粒体的脂肪酸组成以及红细胞膜都没有观察到变化。与对照组相比,环孢素单独产生血浆甘油三酯显著降低,其他脂质参数没有变化。在不同的膜上测量的荧光各向异性没有被几种处理所改变。鉴于上述数据,可以说甲基强的松可能是移植后患者在接受环孢素联合免疫治疗时观察到的许多脂质紊乱的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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