Administration of ciprofibrate to lactating mothers induces PPARalpha-signaling pathway in the liver and kidney of suckling rats.
Morphological and morphometric parameters (volume density (Vv), numerical density (NA) and mean diameter (D)) of newborn liver peroxisomes were measured throughout the first week of life in rats born to mothers treated with clofibrate (ethyl 2 p-chlorophenoxy isobutyrate) during the last five days of pregnancy. In control studies the same analyses were carried out in newborns from untreated rats. At birth (day 0), treated animals exhibited a proliferated, pleiomorphic peroxisomal population (higher Vv, NA and D, and a spread distribution of profile diameter with respect to the controls). In the subsequent two days, many peroxisomes disappeared (decrease of Vv and NA to values even lower than controls), with a persisting high pleiomorphism (no change of D and diameter distribution) in residual ones. Starting from day 3, and up to day 6, larger peroxisomes were no longer detectable in test animals, and a significant, not pleiomorphic proliferation took place (D and diameter distributions strictly comparable to the controls and progressively increasing Vv and NA). The correlation analysis validated these morphological results, from which it can be surmised that the postnatal peroxisome recovery period consists of a destructive phase followed by a proliferative one. The possible mechanism(s) of disposal of the excess of drug-induced peroxisomes are discussed.