Lack of peroxisome proliferation in marmoset liver following treatment with ciprofibrate for 3 years.
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 marmosets 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, alpha-glycerophosphate dehydrogenase, benzphetamine N-demethylase, and ethoxyresorufin O-deethylase were unaffected by treatment with ciprofibrate. Activity of glutathione transferase was increased in the low dosage group but unaffected in the mid and high dosage groups. Modest increases in activities of peroxisomal beta-oxidation (2.5-fold, maximal), carnitine acetyl transferase (1.7-fold, maximal), and carnitine palmitoyl transferase (2-fold, maximal) were observed. Cytochemical staining and quantitative 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 primate 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.
Graham
M J
MJ
Department of Toxicology, Sterling Winthrop Pharmaceuticals Research Division, Alnwick, Northumberland, United Kingdom.
Wilson
S A
SA
Winham
M A
MA
Spencer
A J
AJ
Rees
J A
JA
Old
S L
SL
Bonner
F W
FW
D000818:Animals; D002144:Callithrix; D002995:Clofibric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D058607:Fibric Acids; D008062:Lipofuscin / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron
D058607:Fibric Acids; D008062:Lipofuscin; D002995:Clofibric Acid; C019304:ciprofibrate