Effects of pregnancy and protein-energy malnutrition on monooxygenase O-dealkylation activity in rat liver microsomes

Xenobiotic metabolism is influenced by a variety of physiological and environmental factors including pregnancy and nutritional status of the individual. Pregnancy has generally been reported to cause a depression of hepatic monooxygenase activities. Low-protein diets and protein-energy malnutrition have also been associated with a reduced activity of monooxygenases in nonpregnant animals. We investigated the combined effects of pregnancy and protein-energy malnutrition on liver monooxygenase O-dealkylation activity. On pregnancy day 0 rats were assigned at random to a group fed ad libitum (well-nourished, WN) or to a malnourished group (MN) which received half of the WN food intake (12 g/day). WN and MN rats were killed on days 0 (nonpregnant), 11 or 20 of pregnancy and ethoxy- (EROD), methoxy- (MROD) and penthoxy- (PROD) resorufin O-dealkylation activities were measured in liver microsomes. Only minor changes in enzyme activities were observed on pregnancy day 11, but a clear-cut reduction of monooxygenase activities (pmol resorufin min-1 mg protein-1) was noted near term (day 0 vs 20, means + or _ SD, Student t-test, P<0.05) in WN (EROD: 78.9 + or - 15.1 vs 54.6 + or - 10.2; MROD: 67.8 + or - 10.0 vs 40.9 + or - 7.2; PROD: 6.6 + or - 0.9 vs 4.3 + or - 0.8) and in MN (EROD: 89.2 + or - 23.9 vs 46.9 + or - 15.0; MROD: 66.8 + or - 13.8 vs 27.9 + or - 4.4; PROD: 6.3 + or - 1.0 vs 4.1 + or - 0.6) dams. On pregnancy day 20 MROD was lower in MN than in WN dams. Malnutrition did not increase the pregnancy-induced reduction of EROD and PROD activities. Thus, the present results suggest that the activities of liver monooxygenases are reduced in near-term pregnancy and that protein-energy malnutrition does not alter EROD or PROD in pregnant rats

Study of the embryofeto-toxicity of Crown-of-Thorns (Euphorbia milii) latex, a natural molluscicide

The crude latex of Crown-of-Thorns (Euphorbia milii var. Hislopii) is a potent plant molluscicide and a promising alternative to the synthetic molluscicides used in schistosomiasis control. The present study was undertaken to investigate the embryofeto-toxic potential of E. Milii latex. The study is part of a comprehensive safety evaluation of this plant molluscicide. Lyophilized latex (0, 125, 250 and 500 mg/kg body weight) in corn oil was given by gavage to Wistar rats (N = 100) from days 6 to 15 of pregnancy and cesarean sections were performed on day 21 of pegnancy. The numbers of implantation sites, living and dead fetuses, resorptions and corpora lutea were recorded. Fetuses were weighed, examined for external malformations, and fixed for visceral examination, or cleared and stained with Alizarin red S for skeleton evaluation. A reduction of body weight minus uterine weight al term indicated that E. Milii latex was maternally toxic over the dose range tested. No latex-induced embryolethality was noted at the lowest dose (125 mg/kg) but the resorption rate was markedly increased at 250 mg/kg (62.5 percent) and 500 mg/kg (93.4 percent). A higher frequency of fetuses showing signs of delayed ossification (control: 17.4 percent; 125 mg/kg: 27.4 percent and 250 mg/kg: 62.8 percent; P<0.05 vs control) indicated that fetal growth was retarded at doses ³125 mg latex/kg body weight. No increase in the proportion of fetuses with skeletal anomalies was observed at the lowest dose but the incidence of minor skeletal malformations was higher at 250 mg/kg body weight (control: 13.7 percent; 125 mg/kg: 14.8 percent; 250 mg/kg: 45.7 percent; P<0.05 vs control). Since a higher frequency of minor malformations was noted only at very high doses of latex which are embryolethal and maternally toxic, it is reasonable to conclude that this plant molluscicide poses no teratogenic hazard or, at least, that this possibility is of a considerably low order of magnitude.