Olsson U, Sundberg C, Andersson K, De Pierre J W
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
Biochem Pharmacol. 1993 Nov 17;46(10):1805-10. doi: 10.1016/0006-2952(93)90586-l.
Most effects of the peroxisome proliferator clofibrate on rat liver are marginal or absent in selenium (Se) deficiency. The purpose of the present study was to determine whether the uptake or distribution of clofibrate is altered by Se deficiency. Rats were fed a Se-adequate or -deficient diet for 10-11 weeks and then these same diets with 0.5% (w/w) clofibric acid (the direct acting hydrolysis product of clofibrate) or 0.02% (w/w) perfluorooctanoic acid (PFOA) for 10 days. Other groups of rats received radiolabeled clofibrate by intubation. Clofibric acid was an ineffective as clofibrate in producing effects (i.e. decreased body weight gain, increases in liver somatic index and protein content of the mitochondrial fraction, and increased activities of catalase and peroxisomal fatty acid beta-oxidation) in the liver of Se-deficient rats. Microsomal omega-hydroxylation was, however, equally induced in both dietary groups. In contrast to clofibric acid, the biological effects of PFOA were not affected by Se status. Furthermore, neither the tissue distribution (plasma, liver and kidney) nor the urinary excretion of 14C was affected by Se deficiency. These results demonstrate that the hydrolysis of clofibrate to clofibric acid is not impaired in the Se-deficient rat. In addition, the involvement of Se in the effects of peroxisome proliferators differs for different members of this structurally heterogeneous group of compounds. It is concluded that the Se-deficient rat may provide valuable information concerning the biochemical mechanism(s) underlying peroxisome proliferation.
过氧化物酶体增殖剂氯贝丁酯对大鼠肝脏的大多数作用在硒（Se）缺乏时很轻微或不存在。本研究的目的是确定氯贝丁酯的摄取或分布是否会因硒缺乏而改变。给大鼠喂食含硒充足或缺乏的饲料10 - 11周，然后在这些相同的饲料中添加0.5%（w/w）氯贝酸（氯贝丁酯的直接作用水解产物）或0.02%（w/w）全氟辛酸（PFOA），持续10天。其他几组大鼠通过插管给予放射性标记的氯贝丁酯。在缺硒大鼠肝脏中，氯贝酸在产生效应方面（即体重增加减少、肝脏体指数和线粒体部分蛋白质含量增加以及过氧化氢酶和过氧化物酶体脂肪酸β -氧化活性增加）不如氯贝丁酯有效。然而，微粒体ω -羟基化在两个饮食组中均受到同等程度的诱导。与氯贝酸相反，PFOA的生物学效应不受硒状态的影响。此外，缺硒对14C的组织分布（血浆、肝脏和肾脏）以及尿排泄均无影响。这些结果表明，缺硒大鼠中氯贝丁酯水解为氯贝酸的过程未受损害。此外，对于这一结构异质的化合物组中的不同成员，硒在过氧化物酶体增殖剂效应中的参与情况有所不同。得出的结论是，缺硒大鼠可能为过氧化物酶体增殖的潜在生化机制提供有价值的信息。
