title: Effects of the rat hepatic peroxisome proliferator, Wyeth 14,643, on the lactating goat.
abstract: Some peroxisome proliferators have been reported to reduce body weight gain in suckling rats, possibly through a lactational effect. Decreases in milk production or nutritional quality, either as a result of peroxisome proliferator-induced reductions in lipid content or alterations in the hormonal milieu necessary for milk production, could result in pup growth retardation. Wyeth-14,643 (WY) is hypolipidemic agent and a potent inducer of hepatic peroxisome proliferation in rats and mice. As is commonly seen with rodent hepatic peroxisome proliferators, WY produces minimal or no peroxisome induction in guinea pigs or non-human primates. Goats are an excellent model for studying lactation, however, their sensitivity to peroxisome proliferating chemicals is not known. The present study was performed to assess the sensitivity of goats to the hypolipidemic and peroxisome proliferator properties of WY and to determine the effects of WY on milk quantity and quality. Six lactating adult female goats were assigned to either control or treated groups. Goats in the treated group were administered WY (40 mg/kg/day) for 14 consecutive days. The goats were milked twice daily in order to maintain lactation and the quantity of milk collected was recorded. Milk quality was evaluated by determining the content of total fat, protein, and carbohydrate in milk samples collected following 7 and 14 days of treatment. WY administration had no effects on final body weight, liver weight or, gross and histopathological findings. Milk quantity and quality were unaffected by treatment. Serum cholesterol and triglyceride levels were reduced by 25% compared to controls, although only the difference in cholesterol was statistically significant. Hepatic beta-oxidation (3 x control) and aromatase (1.5 x control) activities were significantly greater in the treatment group; however, there was no treatment-related effect in the total content of hepatic cytochrome P450. There was no difference in aromatase activity in a pooled ovarian microsome sample. Milk estradiol and prolactin concentrations were not affected by treatment. These findings indicate that goats are weak responders to the hepatic peroxisome proliferator effects of WY. Additionally, the slight serum hypolipidemic effect does not impact milk production or nutritional value.
authors.affiliation: Pfizer Global Research and Development, Groton, CT 06340, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Cappon
authors.forename: R C M
authors.initials: RC
authors.lastname: Liu
authors.forename: S R
authors.initials: SR
authors.lastname: Frame
authors.forename: M E
authors.initials: ME
authors.lastname: Hurtt
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001835:Body Weight; D004958:Estradiol / Q000032:analysis; D005260:Female; D006041:Goats; D007774:Lactation / Q000187:drug effects*; D008055:Lipids; D008830:Microbodies; D008892:Milk / Q000737:chemistry*; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats
chemical_list: D008055:Lipids; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D004958:Estradiol; C006253:pirinixic acid