Change of the sex-dependent response to clofibrate in F344 rat liver during postnatal development.
Although it has been reported that male rats are more responsive than females to peroxisome proliferation induced by clofibrate, these sex differences have been confirmed in young adult rats. Using 4-, 8-, and 12-week-old F344 rats, postnatal change of the sex-dependent response to clofibrate was investigated. These animals were administered 200 mg/kg body wt./day clofibrate by gavage for 7 days. In 4-week-old rats clofibrate-dependent changes (hepatomegaly, induction of hepatic microsomal and peroxisomal enzymes, proliferation of smooth endoplasmic reticulum and peroxisomes of hepatocytes) were slight in both sexes. In 8- and 12-week-old rats clofibrate-induced changes of males were moderate, whereas those of females were slight. These results suggest that the responsiveness of immature rat to clofibrate is weak and in males the susceptibility is gradually strong during postnatal development.
Yamoto
T
T
Laboratory Animal Science and Toxicology Laboratories, Sankyo Co. Ltd., Shizuoka, Japan.
Ohashi
Y
Y
Furukawa
T
T
Teranishi
M
M
Manabe
S
S
Makita
T
T
D000284:Administration, Oral; D000375:Aging; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000008:administration & dosage / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D002994:Clofibrate