Oxidative damage in pregnant diabetic rats and their embryos

Free radical mechanisms may be involved in the teratogenesis of diabetes. T he contribution of oxidative stress in diabetic complications was investiga ted from the standpoint of oxidative damage to DNA, lipids, and proteins in the livers and embryos of pregnant diabetic rats. Diabetes was induced pri or to pregnancy by the administration of streptozotocin (45 mg/kg). Two gro ups of diabetic rats were studied, one without any supplementation (D) and another treated during pregnancy with vitamin E (150 mg/d by gavage) (D + E ). A control group was also included (C). The percentage of malformations i n D rats were 44%, higher than the values observed in C (7%) and D + E (12% ) animals. D Group rats showed a higher concentration of thiobarbituric aci d reactive substances in the mother's Liver, however, treatment with vitami n E decreased this by 58%. The levels of protein carbonyls in the liver of C, D, and D + E groups were similar. The "total levels" of the DNA adducts measured, both in liver and embryos C groups were similar to the D groups. Treatment of D groups with vitamin E reduced the levels by 17% in the liver and by 25% in the embryos. In terms of the "total levels" of DNA adducts, the embryos in diabetic pregnancy appear to be under less oxidative stress when compared with the livers of their mothers. Graziewicz et al. (Free Rad ical Biology & Medicine, 28:75-83, 1999) suggested "that Fapyadenine is a t oxic lesion that moderately arrests DNA synthesis depending on the neighbor ing nucleotide sequence and interactions with the active site of DNA polyme rase." Thus the increased levels of Fapyadenine in the diabetic livers and embryos may similarly arrest DNA polymerase, and in the case of this occurr ing in the embryos, contribute to the congenital malformations. It is now c ritical to probe the molecular mechanisms of the oxidative stress-associate d development of diabetic congenital malformations. (C) 2000 Elsevier Scien ce Inc.