1. Investigación

Postnatal development of the glucose and insulin balance in offspring of ethanol-treated and control rats has been studied. Newborn rats were separated from their mothers and placed with normal lactating, nonethanol-treated dams. Prenatal exposure to ethanol led to hypoglycemia on the first day of extrauterine life and a general tendency to hyperinsulinemia during the entire postnatal period studied. The glucose-tolerance test in weaned rats (30 days old) gave a greater and faster increase than controls in levels of both glucose and plasma insulin. At adult age (90 days) the response of blood glucose to an oral glucose load in offspring from ethanol-treated mothers was not different from that in offspring from controls, but the insulin response was higher. This abnormal insulin response, such a long time after the end of ethanol exposure, suggests either a permanent alteration in the pancreatic response, or a peripheral insulin resistance and/or differences in the rate of insulin degradation in these animals.

From parturition, lactating Wistar rats were given 20% ethanol in drinking water and solid diet ad lihitum (ET group) or were pair-fed to the ET group (PF group) or were given water and solid diet ad lihitum (control group, C). Animals were studied on day 12 of lactation and/or treatment, when dams were separated from their litters and 2-4 hours latter they were i.p. injected with oxytocin for milk collection under anaesthesia. Maternal food intake, weight gain and pup's body weight were lower in ET than in C rats. When compared to C rats, milk of ET dams had a decreased proportion of C14:0 and C22:6 n-3 fatty acids while an increase in C18:0, C16:1 and C18:1 n-9 was detected, whereas when compared to PF it had higher CS:0, Cl0:0, C18:0, C18:1 n-9, C18:2 n-6 and lower C20:5 n-3 and C22:6 n-3. Body weight was lower in pups from ET than in those from C or PF, and whereas brain weight and brain lipid content was lower in ET and PF pups than in C, total phospholipid (PL) brain content was similar among the groups. The ratio of C20:3 n-9 to C20:4 n-6 in brain PL was higher in ET pups than in either C or PF, indicating an essential fatty acid deficiency in the formers. Ethanol treatment also decreased the proportional amount of C18:2 n-6, C18:3 n-3, C20:4 n-6, C20:5 n-3 and C22:6 n-3 in brain PL as compared to C, whereas from these fatty acids only C18:3 n-3, C20:5 n-3 and C22:6 n-3 were decreased in PF. On the other hand, the proportion of C22:6 n-3 was significantly lower in the pups of ET group than in PF animals. Present results show that maternal intake of ethanol during lactation in the rat modifies milk lipid composition and that these effects are not caused by the undemutrition condition of the animals. These effects alter fatty acid composition of brain PL in pups, and such effect may contribute to its abnormal development.

Addition of ethanol ( ET) to the drinking fluid of pregnant rats has been questioned as an experimental model for the fetal alcohol syndrome (FAS). This model, however. closely simulates human alcohol intake, and in this study we used a modified version of previous protocols to overcome their major defects. A group of female rats was given I 07r ET in drinking fluid for one week, 15'/r for the second week. 20'/r for the third, and 251/r for the fourth, at the end of which they were mated with non-treated males and given 251/r ET throughout gestation. Three groups of non-ET treated sex and age-matched rats were studied in parallel: (I) normal controls receiving solid diet ad lib. (2) paired fed rnts, and (3) rats fed ad lib the solid diet mixed with 50'/r fiber. In the ET group, food intake decreased as ET consumption augmented, the ET calories comprising over 3(flr of the total energy intake during pregnancy. Total energy intake was similar for ET group and normal controls, and was higher than in paired fed animals or those on 5(f/r fiber diet. Body weight gain in ET rats was similar to those on 50'/r fiber diet, lower than in normal controls and higher than in paired fed animals. At the 21st day of gestation. rats on ET had plasma ethanol levels of 147:+: 18 mg/di and higher plasma osmolality than in the other groups studied. In ET rats, fetal body weight was lower than in either normal controls or rats on 5(f/r fiber diet, and fetal body length was shorter than in any other group. These findings demonstrate that our protocol provides a suitable animal model for the study of FAS, and indicate that rats on 507r fiber diet are better control subjects than paired fed rats.

Chronic and acute ethanol treat nents increased th,: 3-hydroxybutyrate uptake by lactating rat mammary gland as :1 consequence of its high afferent concentration, without changing its relative extraction. The uptake of glucose was inhibited in the ethanol treated animals due to int ·insic alterations in the mammary gland metabolism as indicated by the decreased relative extrac1 ion and unchanged afferent concentration. These results would suggest that the ek:vated uptake of ketone bodies in ethanol-treated rats can be respcnsible, at least in part, for the decrease in glucose uptake by lactating rat mammary gland, although other direct effects of ethanol may be implied.