Science Inventory

ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

Citation:

Hunter, E S. AND E H. Rogers. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO. Presented at Teratology Society Meeting, Palm Beach, Florida, June 23-28, 2000.

Description:

Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC.

Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxidative damage was responsible for induction of exencephaly and axial skeletal defects by arsenicals in vivo. PBN (N-t-butyl-a-phenylnitrone, an antioxidant spin trap) was administered (41.5mg/kg) 2 hours before sodium arsenite (12.5mg/kg)[As3] or arsenate (40mg/kg)[As5] on gestation day (GD) 8 in CD-1 mice, all by IP injection. On GD 19, implants, resorptions, live, dead and exencephalic (EX) fetuses were counted and body weights measured (n=9-14 litters). The axial skeleton was evaluated in alizarin red-stained fetuses. Following As3 treatment, lethality was observed in 61% of implantations/litter, but with PBN pretreatment lethality was 39% (p=0.288). EX was present in 41% of fetuses/litter in As3 and 16% in As3+PBN (p = 0.108). Fetal weights increased from 1.10g to 1.26g per fetus with PBN pretreatment (p=0.025). PBN did not ameliorate As5-induced effects (e.g., 62% compared to 59% EX fetus/litter). PBN pretreatment did not reduce skeletal fusions or alter the number of ribs in As3 or As5 treated fetuses (n=3-5 litters). Thus, oxidative damage contributes to the adverse effects produced by As3, but there are multiple mechanisms responsible for the full spectrum of effects. The lack of PBN-induced protection following As5 exposure suggests that there are differences in the mechanisms responsible for As3 and As5-induced developmental effects. This abstract does not present US EPA policy.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 06/23/2000
Record Last Revised: 06/21/2006
Record ID: 60465