Ciriolo M R, Rossi L, Mavelli I, Rotilio G, Borzatta V, Cristofori M, Barbanti M
Arzneimittelforschung. 1984;34(4):465-7.
Male and female rats were treated with hypolipidemic agents derived from procetofenic acid, namely fenofibrate ( procetofene ), cholestyrammonium alpha-(4-p-chlorobenzoyl-phenoxy)-isobutyrate (Alfa-1081) and alpha-(4-p-chlorobenzoyl-phenoxy)-isobutyryl-taurine (35/ipo). A marked decrease of liver superoxide dismutase and glutathione peroxidase was observed in the male rats treated with fenofibrate. In this sample a significant increase of malonyl dialdehyde was also detected when the liver homogenates were subjected to a test of lipid peroxidation induced by active oxygen species. Alfa-1081 and 35/ipo produced no substantial changes of superoxide dismutase and glutathione peroxidase and no significant increase of peroxidation products. These results, while providing an in vivo evidence for the role of superoxide dismutase and glutathione peroxidase as antioxidant enzymes, indicate that hypolipidemic agents can affect also enzymes not bound to membranes as they do with peroxisomal enzymes. The side effect presented here may be harmful, since it can lead to an augmented risk of lipid peroxidation in tissues. It is, however, clear that also within the same class of hypolipidemic drugs the effect is not always present. Peroxidative damage should therefore be considered as a key parameter in the characterization of hypolipidemic agents.
对雄性和雌性大鼠使用了源自普罗布考芬酸的降血脂药物，即非诺贝特（普罗布考）、α-(4-对氯苯甲酰苯氧基)-异丁酸胆碱铵（Alfa-1081）和α-(4-对氯苯甲酰苯氧基)-异丁酰牛磺酸（35/ipo）。在用非诺贝特治疗的雄性大鼠中，观察到肝脏超氧化物歧化酶和谷胱甘肽过氧化物酶显著降低。在该样本中，当肝脏匀浆进行活性氧诱导的脂质过氧化试验时，还检测到丙二醛显著增加。Alfa-1081和35/ipo对超氧化物歧化酶和谷胱甘肽过氧化物酶没有产生实质性变化，过氧化产物也没有显著增加。这些结果在为超氧化物歧化酶和谷胱甘肽过氧化物酶作为抗氧化酶的作用提供体内证据的同时，表明降血脂药物也可以影响与膜不结合的酶，就像它们对过氧化物酶体酶的作用一样。这里呈现的副作用可能是有害的，因为它会导致组织中脂质过氧化风险增加。然而，很明显，即使在同一类降血脂药物中，这种作用也并非总是存在。因此，过氧化损伤应被视为降血脂药物特性描述中的一个关键参数。
