1. Investigación

Nuestros resultados permiten sugerir que la administración de antioxidantes capaces de reducir la producción de radicales libres, podrían desempeñar un importante papel en la prevención de los efectos teratogénicos asociados a la diabetes. Tal vez lo más relevante es que los antioxidantes actuarían independientemente del grado de control metabólico alcanzado, por lo que sus efectos podrían añadirse a los conseguidos al obtener un mejor control metabólico.

The aim of the present study was to determine in the BALB/c mice, a model of development of atherosclerosis when both hyperglycemia and hypercholesterolemia are present, whether the atherogenic effects of these parameters could be decreased with the administration of Vitamin E. BALB/c mice were made diabetic and divided in three groups: one fed the standard rodent chow diet (D); the other two fed an atherogenic diet (D + A); one of them supplemented with Vitamin E (D +A+ E). Two groups of non diabetic animals were also performed, one fed the standard diet (C) and the other the atherogenic diet (C + A). After 16 weeks of treatment all the control animals survived, in contrast, a mortality rate of 12, 70 and 37% was observed, respectively, in the D, D + A and D +A+ E groups. Neither fatty deposits nor macrophages were observed in the arterial wall of the animals fed the standard diet (D and C animals). In contrast, this finding was observed in 25% of the C + A, 71% of the D + A and 33% of the D +A+ E. In conclusion, diabetic mice fed an atherogenic diet showed in the aorta a higher number of fatty deposits and macrophages than the control animals. These effects were partially reversed with the administration of Vitamin E, supporting in this model the role of oxidative stress in the development of atherosclerosis.

Free radical mechanisms may be involved in the teratogenesis of diabetes. The contribution of oxidative stress in diabetic complications was investigated from the standpoint of oxidative damage to DNA, lipids, and proteins in the livers and embryos of pregnant diabetic rats. Diabetes was induced prior to pregnancy by the administration of streptozotocin (45 mg/kg). Two groups 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 in Drats were 44%, higher than the values observed in C (7%) and D + E (12%) animals. D Group rats showed a higher concentration of thiobarbituric acid reactive substances in the mother's liver, however, treatment with vitamin 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 Radical Biology & Medicine, 28:75-83, 1999) suggested "that Fapyadenine is a toxic lesion that moderately arrests DNA synthesis depending on the neighboring nucleotide sequence and interactions with the active site of DNA polymerase." Thus the increased levels ofFapyadenine in the diabetic livers and embryos may similarly arrest DNA polymerase, and in the case of this occurring in the embryos, contribute to the congenital malformations. It is now critical to probe the molecular mechanisms of the oxidative stress-associated development of diabetic congenital malformations.