Effects of selenium supplementation on hepatocarcinogenesis in rats.

Four groups of weanling male Wistar rats (Groups A-D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast-based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair-feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.

Acute adriamycin cardiotoxicity in rats.

To explore the possible occurrence and pathogenic implications of in vivo heart lipoperoxidation in the acute model of ADR-cardiotoxicity, male Wistar rats were injected i.v. with a single dose of ADR (15 mg/kg) and the controls with saline. The rats were killed at 24 and 96 hr after treatment and at the later period the serum levels of creatine kinase of ADR-treated rats were significantly elevated. ADR-treatment did not significantly modify the cardiac concentrations of DNA, RNA, protein, the levels of activity of cardiac catalase and GSH-Px or the in vitro production of malonaldehyde of cardiac homogenates. Mitochondrial swelling at 24 hr and reduction of the mitochondrial numerical and volumetric densities along with myofilament fragmentation at 96 hr were the most significant ultrastructural changes in cardiac myocytes of ADR-treated rats. Although in vivo lipoperoxidation (diene conjugation) was detected in the cardiac lipids of only 2 out of 6 rats at 24 hr and in 3 out of 6 rats at 96 hr, no clear correlation could be found between the eventual presence of this in vivo phenomenon and any of the cardiac changes. These data suggested that lipoperoxidation may not play a fundamental role in the pathogenesis of acute ADR-cardiotoxicity in rats.