Investigations on the presence of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase, E.C.1.1.1.34) in lenses of various animal species.

Lens and eye toxicity research Pub Date : 1990-01-01
M Kojima, O Hockwin, G S Rao, J Garcia
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Abstract

The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis immediately after birth, this capacity, however, decreases considerably with increasing age, so that the deficit can only be met by exogenous supply. These findings are of great importance with respect to the qualitative assessment of extra-hepatical side effects of the substance class of HMG-CoA-reductase inhibitors on possible disturbances of lens transparency. In contrast to investigations of Mosley et al. (23) with rat and rabbit lenses, we did not find any activity of the HMG-CoA-reductase in our experiments with the lens cortex of calf, bovine, Beagle dog. The disturbances in lens transparency observed in chronical toxicity tests with high doses of HMG-CoA- reductase inhibitors might rather be due to the impairment of the exogenous cholesterol supply by a considerable decrease of the normal cholesterol level in the blood. The therapeutical treatment of pathologically increased blood cholesterol levels of patients should therefore not affect the transparency of human lenses. Relevant drug-safety-clinical studies confirm this experimentally substantiated supposition.

3-羟基-3-甲基戊二酰辅酶A还原酶(hmg - coa -还原酶,e.c 1.1.1.34)在不同动物晶状体中的存在研究。
晶状体形成质膜所需的胆固醇在出生后立即通过自我合成来满足,然而,这种能力随着年龄的增长而显著下降,因此只能通过外源供应来满足缺陷。这些发现对于定性评估hmg -辅酶a还原酶抑制剂类物质对晶状体透明度可能的干扰的肝外副作用具有重要意义。与Mosley等人(23)对大鼠和兔晶状体的研究相反,我们在小牛、牛、比格犬的晶状体皮层实验中没有发现任何hmg -辅酶a还原酶的活性。在使用高剂量HMG-CoA-还原酶抑制剂的慢性毒性试验中观察到的晶状体透明度的紊乱可能是由于血液中正常胆固醇水平的显著降低导致外源性胆固醇供应的损害。因此,对病理性升高的患者血液胆固醇水平的治疗不应影响人体晶状体的透明度。相关的药物安全临床研究证实了这一实验证实的假设。
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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