1. Investigación

We wanted to determine whether administration of vitamin E could reduce the production of free radicals which could play a role in the teratogenic effects of diabetes mellitus. Diabetes was induced in Wistar rats by the intravenous administration of streptozotocin. The animals were divided into six groups: one with no supplement (D) and two, supplemented during pregnancy either with oral vitamin E (150 mg/day) (D + E) or with a placebo (safflower oil) (D + 0). Three other groups were kept under the same conditions, but were treated with insulin: D + I, D + I + E and D + I + 0. There were three groups of matched controls: C, C + E and C + 0. All animals were killed on day 11.5 of pregnancy. In C animals the percentages of reabsorptions and malformations were 1.3 and 2 %, respectively, comapred with 23.6, 24.3, 6.2 and 13.2 %, respectively in D and D + I groups. The crown-rump length, number of somites, and protein and DNA content were: higher in C animals than in the diabetic rats, independent of insulin treatment. When vitamin E was administered no changes in these parameters were observed in C and D + I animals; however, in the D mothers it reduced the rate of embryo malformations to 4.6 % and increased the crown-rump length and the number of somites. However, vitamin E did not modify the protein and DNA content and the percentage of reabsorptions. In conclusion, administration of vitamin E to diabetic animals decreases the rate of embryo malformations and increases their size and maturation, supporting a role for free radicals in the teratogenic effects of diabetes.

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (IV) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance.

We wanted to determine whether alphatocopherol supplementation to pregnant rats could increase the concentration of alphatocopherol in maternal and fetal plasma and tissues. Pregnant rats were treated with alpha-tocopherol on days 18 and 19 gestation and studied at day 20. A control group was studied in parallel. Treatment of pregnant rats with alpha-tocopherol increased its concentration in maternal and fetal plasma, in all maternal plasma lipoprotein fractions, in maternal and fetal liver and in the placenta. The fetal and maternal concentration of alphatocopherol were positively correlated.