Exposure to inorganic arsenite alters glucose metabolism of pregnant rats

BONAVENTURA MM; BOURGUIGNON N; LIBERTUN C; LUX LANTOS V

Houston

Congreso; ENDO 2012; 2012

The Endocrine Society

Exposure to inorganic arsenite alters glucose metabolism of pregnant rats   Bonaventura M1, 2, Bourguignon N1, Libertun C1, 2, Lux-Lantos V1. 1 IBYME-CONICET, 2 UBA   mmbonaventura@gmail.​com     Inorganic arsenic is a worldwide distributed natural contaminant. The most common source of contamination is from ground water. Inorganic arsenic is highly toxic and a proved carcinogenic in humans. Recently it has also been described as an endocrine disruptor impacting the metabolic and reproductive axes, although the mechanisms have not been elucidated. Female Sprague-Dawley rats were treated with sodium arsenite in drinking water (5 or 50 ppm in distilled water or distilled water as control) from gestation day 1 (GD1) (confirmed by presence of vaginal sperm plug) to sacrifice (two months post-partum). Standard chow was given ad libitum. Body weight (BW) was recorded during pregnancy and on GD15-17, a glucose tolerance test (GTT) was performed. Additionally, dams were evaluated by a GTT one month after weaning. For GTTs, intraperitoneal glucose (2 g/kg BW) was injected to overnight-fasted rats and blood glucose levels were evaluated at different time points. On postnatal day 1 (PND1), pups were counted, sexed and weighted. Results are expressed as means ± S.E.M. Differences between means were analyzed by one-way ANOVA or two?way ANOVA with repeated measures design. P<0.05 was considered statistically significant. No differences were found on BW during pregnancy. The GTT was significantly altered in pregnant animals treated both with 5 or 50 ppm of sodium arsenite (A5 and A50, respectively), being the glycemia at 30 minutes post glucose overload significantly higher in treated animals compared to controls (mg/dl: C: 171 ± 10, A5: 281 ± 21, A50: 290 ± 22; A50, A5 vs. C, p<0.001, n= 6-8). However, the GTT performed one month after weaning showed no differences between groups. Dams from all groups delivered their offspring at 23 days and no differences were observed on litter size and litter sex. BW of pups on PND 1 was significantly diminished in the A50 pups from both sexes, compared with controls; no differences were observed in A5 treated animals [BW (g): Female pups: C: 7.7 ± 0.1, A5: 7.9 ± 0.1, A50: 7.3 ± 0.1; A50 vs. C, A5, p<0.05, n=39 for each group; Male pups: C: 8.1 ± 0.1, A5: 8.1 ± 0.1, A50: 7.6 ± 0.1; A50 vs. C, A5 p<0.005. n= 31-40]. We conclude that exposure to sodium arsenite during pregnancy produces a clear alteration in glucose homeostasis on dams, probably inducing the alterations on body weight observed in their pups. These results suggest that inorganic arsenic could alter the metabolism of both dams and their offspring.   (CONICET-UBA-ANPCYT).