Dehydroepiandrosterone sulfate and cytochrome P450 inducers alleviate fatty liver in male rats fed an orotic acid-supplemented diet.

The effects of the peroxisome proliferator, dehydroepiandrosterone sulfate (DHEAS), and the typical cytochrome P450 (CYP) inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) on fatty liver were examined in rats. Treating rats with orotic acid caused marked accumulation of lipid droplets in the liver. This effect of orotic acid was almost eradicated by co-treatment with DHEAS and PB. While DHEAS or PB alone also alleviated fatty liver, treatment with 3-MC caused little effect on a reduction in lipid droplets. Histopathological examinations revealed numerous peroxisomes in the liver of rats treated with DHEAS. In addition, a significant increase in the expression on hepatic CYPs was observed in rats the fatty liver of which was attenuated. Regarding other enzymes associated with hepatic fatty acid oxidation, the expression levels of sirtuin 1, sirtuin 6, and carnitine palmitoyltransferase 1 were also upregulated most markedly by treatment with DHEAS alone. Thus, the attenuation in fatty liver observed in the present study is likely due to peroxisome proliferation and the induction of fatty acid-metabolizing enzymes by DHEAS and typical CYP inducers.

[Enzymatic induction with phenobarbital and 3-methylcholanthrene in rats exposed to normobaric oxygen]. / Induction enzymatique par le phénobarbital et par le 3-méthylcholanthrène chez le rat exposé à l'oxygène normobare.

Induction by phenobarbital and 3-methylcholanthrene of enzymes metabolizing xenobiotics in rat exposed 55 hrs to hyperoxia, is maintained. The level of microsomal pulmonary and hepatic cytochrome P-450 has even increased. In rat protected against a hyperoxia 6 days, stimulation of UDP-glucuronosyltransferase does not decrease and malondialdehydes level does not change. These results assume the probable role of enzymatic induction in the tolerance to hyperoxia induced in rast by treatment with phenobarbital and 3- methylcholanthrene.

[Protection of the pulmonary toxic effects of normobaric oxygen by inducers of cytochrome P450-linked monooxygenases]. / Protection des effets toxiques pulmonaires de l'oxygène normobare par les inducteurs enzymatiques des mono-oxygénases liés au cytochrome P450.

Inducers of cytochrome P450-linked mono-oxygenases increase the normobaric oxygen tolerance of the adult rat. Pulmonary inducers, as 3-methylcholanthrene and beta-naphthoflavone permit the rat survival and simultaneously a decrease of pulmonary edema. Phenobarbital, an hepatic inducer had lesser effects both on survival rate and on pulmonary and lymphoïd oxygen toxicity.

[Change of toxic and antineoplastic properties of ftorafur by means of action on nonspecific microsomal oxidase]. / Izmenenie toksicheskikh i protivoopukholevykh svoistv ftorafura putem vozdeistviia na nespetsificheskie oksidazy mikrosom.

The inducers of microsomal hydroxylases, phenobarbitone and methylcholanthrene, inhibited the development of neurotoxic shock provoked by high doses of ftorafur in mice, but stimulated the animal mortality on the 4th-8th day after the drug administration. The opposite effect on both toxicity manifestations has been obtained under the action of the inhibitor SKF 525-A. Pretreatment of the animals with phenobarbitone or phenobarbitone-methylcholanthrene combination markedly increased the antineoplastic activity of ftorafur determined by a loss of the spleen weight in mice infected with Rauscher's leukemia.

Protective action of polycyclic hydrocarbons against induction of adrenal necrosis by dimethylbenzanthracene.

Treatment of rats with certain polycyclic hydrocarbons shifts the hydroxylation of dimethylbenzanthracene (DMBA) by liver microsomes from the side-chain to the ring. Protection by these hydrocarbons against dimethylbenzanthracene-induced adrenal necrosis is possibly achieved by decreasing the yield of the 7-hydroxymethyl derivative of dimethylbenzanthracene which may act as the necrotic agent by virtue of its strutctural resemblance to the adrenocortical steroids.