Effect of the peroxisome proliferator ciprofibrate on hepatic DNA synthesis and hepatic composition following partial hepatectomy in rats.
The peroxisome proliferator ciprofibrate was examined for its ability to alter liver regrowth following partial hepatectomy in rats. Ciprofibrate was fed to female Sprague-Dawley rats at concentrations of 0, 0.01% and 0.025% in the diet for 2 weeks. All rats were then subjected to partial hepatectomy and were killed at 0, 12, 24, 36, 48, 72, and 168 h afterwards. The increase in liver weight after partial hepatectomy occurred at a similar rate in control and ciprofibrate-fed rats, although liver weights were always higher in ciprofibrate-fed rats. The marked increase in DNA synthesis normally seen after partial hepatectomy, however, was partially inhibited in rats fed 0.025% ciprofibrate, as compared to control rats or rats fed 0.01% ciprofibrate. An increase in the ratio of protein to DNA in the liver was observed in rats fed either level of ciprofibrate. The marked increase in total lipid content normally seen after partial hepatectomy was inhibited by ciprofibrate treatment. Vitamin E levels were also reduced in ciprofibrate-fed rats. The activity of the peroxisomal enzyme fatty acyl CoA oxidase was increased in rats fed ciprofibrate at all time points, verifying the induction of peroxisomes by ciprofibrate. This study shows that the administration of 0.025% ciprofibrate before partial hepatectomy inhibits the peak of DNA synthesis normally seen shortly after partial hepatectomy but does not affect the regrowth of the liver. The regrowth of the liver in rats fed 0.025% ciprofibrate may be caused by cellular hypertrophy, as evidenced by the enhanced protein content of the liver.
Srinivasan
S R
SR
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506.
Chow
C K
CK
Glauert
H P
HP
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D005260:Female; D058607:Fibric Acids; D006498:Hepatectomy; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000378:metabolism
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D014810:Vitamin E; D002995:Clofibric Acid; D004247:DNA; C019304:ciprofibrate; D002994:Clofibrate