大鼠肝脏和肾脏过氧化物酶体对新型降血脂药物RMI 14,514的异常反应。
Unusual responses of rat hepatic and renal peroxisomes to RMI 14, 514, a new hypolipidemic agent.
作者信息
Svoboda D J
出版信息
J Cell Biol. 1978 Sep;78(3):810-22. doi: 10.1083/jcb.78.3.810.
RMI 14, 514 ([5-tetradecycloxy]-2-furancarboxylic acid) represents a new class of hypolipidemic agents which cause unusual ultrastructural changes in liver of male rats and in selected peroxisomal enzymes in liver and kidney of both sexes. Among the principal ultrastructural changes in peroxisomes of male rat liver were (a) cavitation and compartmentalization of the matrix, often giving the appearance of a peroxisome-within-a-peroxisome, and (b) narrow, dense extensions of canaliculi or cisterns from the periphery of the peroxisome, forming partial circlets or surrounding irregular areas of cytoplasm. The unusual enzyme responses were (a) elevation of catalase activity in liver and kidney in female rats, (b) increased activity of three hydrogen peroxide-producing oxidases (urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase) in the liver of both sexes, and (c) elevation of activity of the last two oxidases in male kidney. The peculiar ultrastructural changes in liver peroxisomes combined with the responses of selected peroxisomal enzymes represent unusual modulations or adaptations of these organelles to a hypolipidemic agent, the effects of which have not been reported extensively.
RMI 14,514（[5-十四烷基氧基]-2-呋喃羧酸）代表一类新型的降血脂药物，它会在雄性大鼠的肝脏以及雌雄两性大鼠肝脏和肾脏中的某些过氧化物酶体酶上引起异常的超微结构变化。雄性大鼠肝脏过氧化物酶体的主要超微结构变化包括：（a）基质出现空泡化和分隔，常常呈现出一个过氧化物酶体内含一个过氧化物酶体的外观；（b）过氧化物酶体周边的小管或池形成狭窄、致密的延伸，形成部分小环或围绕不规则的细胞质区域。异常的酶反应包括：（a）雌性大鼠肝脏和肾脏中过氧化氢酶活性升高；（b）两性大鼠肝脏中三种产过氧化氢的氧化酶（尿酸氧化酶、L-α-羟基酸氧化酶和D-氨基酸氧化酶）活性增加；（c）雄性大鼠肾脏中后两种氧化酶活性升高。肝脏过氧化物酶体中独特的超微结构变化与某些过氧化物酶体酶的反应相结合，代表了这些细胞器对一种降血脂药物的异常调节或适应，其效果尚未得到广泛报道。
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