Lack of Peroxisome Proliferation in Marmoset Liver Following Treatment with Ciprofibrate for 3 Years

Abstract

The effect of treatment of marmosets with ciprofibrate for 3 years on activities of hepatic enzymes, hepatic histomorphology, and ultrastructure were investigated. Male and female mar mosets were dosed with ciprofibrate (2, 10, and 20 mg/kg) by oral gavage once daily for 3 years. No effect on liver weight (adjusted for body weight) or liver morphology was observed. The activities of catalase, glutathione peroxidase, α-glycero phosphate dehydrogenase, benzphetamine N-dernethylase, and ethoxyresorufln O-deethylase were unaffected by treatment with ciprofibrate. Activity of glutathione transferase was in creased in the low dosage group but unaffected in the mid and high dosage groups. Modest increases in activities of peroxiso mal β-oxidation (2.5-fold, maximal), carnitine acetyl transfer ase (1.7-fold, maximal), and carnitine palmitoyl transferase (2- fold, maximal) were observed. Cytochemical staining and quan titative image analysis failed to indicate any effect on peroxisomal number, size, or volume density. Similarly, there was no increase in lipofuscin deposition. This study provides data on the effects of a potent peroxisome proliferator on pri mate liver following a dosing period much greater than that used in previously published studies and is further evidence that the marmoset is relatively insensitive to the well-documented effects that ciprofibrate and other peroxisome proliferators have on rat liver.