Impaired Hepatic Heme Synthesis in the Phenobarbital-Stimulated Selenium-Deficient Rat

Abstract

In 1957 Schwarz and Foltz (1) described an association between dietary selenium deficiency and hepatic necrosis. However, although the dietary requirement for selenium is established, its possible role in the maintenance of normal hepatic function remains speculative. Diplock et al. (2, 3) have recently suggested that selenium may be incorporated into a nonheme iron containing microsomal protein active in the NADPH-dependent electron transfer chain. It is conceivable, therefore, that the integrity of the hepatic microsomal mixed-function oxidase system may in part be dependent on an adequate dietary supply of selenium.

We have recently described an impaired inducibility by phenobarbital of cytochrome P ₄₅₀ and cytochrome b ₅ in the selenium deficient rat (4). The normal inducibility of the flavoprotein component of the mixed function oxidase system, NADPH cytochrome c reductase, in these animals suggested that the impaired response in these selenium deficient rats may be limited to the hemecontaining microsomal proteins. Preliminary observations (4) indicated that the apoprotein component of cytochrome P ⁴⁵⁰ was induced by phenobarbital in the selenium deficient rats. The present study is a continuing investigation of the possible discoordinated synthesis of heme and apoprotein in the selenium deficient phenobarbital-stimulated rat.

Materials and methods. Male Holtzman rats weighing 60–90 g were placed on a selenium deficient torula yeast diet (5) and water ad lib. Two dietary groups were formed by the addition of supplemental selenium, 0.5 mg/kg as Na₂SeO₃, to the diet of one group of animals. Thus, a “selenium replete” and “selenium deficient” group was formed; the animals were maintained on this diet for 3 months, at which stage animals in both groups weighed 300–350 g.

Four animals from each group were then subdivided into two further groups. Within each dietary group two animals received a daily intraperitoneal injection of phenobarbital (80 mg/kg in 0.9 NaCl) for 5 days, the remaining two animals receiving only the vehicle.