Administration of ciprofibrate to lactating mothers induces PPARalpha-signaling pathway in the liver and kidney of suckling rats.
It is well known that the hypolipidemic drug ciprofibrate induces peroxisome proliferation in rodent liver, which in turn leads to the oxidative stress, and modifies some parameters related to cell proliferation and apoptosis. The administration of ciprofibrate to rats during the lactating period determined in their pups significant modifications in hepatic peroxisome enzyme activities, induction of the PPARalpha-target gene, Cyp4a10, and perturbation in cell proliferation and apoptosis, which affected the size of the liver. Moreover, this modification was associated to about two-fold induction of mRNA-PPARalpha. On the contrary, in the kidney, although a similar two-fold up-regulation of PPARalpha was detected, the induction of both peroxisomal enzyme activities and Cyp4a10 were weak, and no alterations were detected, neither in cell cycle nor in the size of the tissue. Our results indicate that the response to ciprofibrate is stronger in the liver than in the kidney of newborn rats.
Fidaleo
Marco
M
Department of Cellular and Developmental Biology, University of Rome La Sapienza, Piazzale Aldo Moro 5, Rome, Italy. marco.fidaleo@uniroma1.it
Sartori
Claudia
C
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D042926:Cytochrome P-450 CYP4A / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D058607:Fibric Acids; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007774:Lactation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018811:Maternal Exposure; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D012333:RNA, Messenger; D002995:Clofibric Acid; D042926:Cytochrome P-450 CYP4A; C019304:ciprofibrate