Morphometric evaluation of species differences in the effects of bezafibrate, a hypolipidemic agent, on hepatic peroxisomes and mitochondria.

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In order to demonstrate the species differences in the effects of a hypolipidemic agent, bezafibrate, on hepatic peroxisomes and mitochondria, bezafibrate a hypolipidemic agent was administered orally to rats, mice, guinea pigs, rabbits, and dogs for two weeks, and to monkeys for 13 weeks. Peroxisomes in the livers were visualized using a cytochemical staining method for catalase with diaminobenzidine. Morphometric comparison of the hepatic peroxisomes and mitochondria was made to examine by point counting method. Peroxisome proliferation was the highest among male rats (4.15 fold) and then male and female mice (3.68 fold and 4.47 fold respectively), with a more moderate increase of this organelle in guinea pigs and monkeys, whereas no change was seen in rabbits and dogs. A slight increase in the volume density of mitochondria was observed for female rats, guinea pigs, and male and female monkeys. These results show that there are marked species differences in the effects of bezafibrate on hepatic peroxisomes and mitochondria. We considered that the species differences are very important to elucidate the mechanism of peroxisomal proliferation, hypolipidemic action, carcinogenicity, and their relationship.