Melvin Lee

Placental blood flow in rats fed alcohol before and during gestation

Abstract Female Sprague-Dawley rats were either given 20% alcohol in drinking water and solid diet ad libitum (alcohol group) or were pair-fed to the alcohol group (pair-fed group) or were given water and solid diet ad libitum (ad libitum group) for four weeks. They were then mated and the alcohol group was changed to 30% alcohol in water. On day 20 of gestation each rat was injected with 57Co-labeled microspheres into the left ventricle and radioactivity was determined in the placentas and kidneys. Cardiac output and blood flow to the placentas and kidneys was calculated. Fetuses and placentas were weighed, and the osmolality of the maternal plasma and water content of the muscle was determined. Cardiac output and blood flow to the kidneys did not differ among the three groups. Blood flow to the placenta, whether expressed as m1/min/g placenta or m1/min/placenta, or as % of cardiac output was significantly reduced in the alcohol group compared with the pair-fed and ad libitum groups, which did not differ from one another. Fetuses were significantly lighter and placentas were significantly heavier in the alcohol group than in the other two groups. Plasma osmolality was increased and muscle water was decreased about 7% in the alcohol group, indicating a moderate degree of dehydration. It is concluded that chronic alcohol consumption leads to a redistribution of blood, with less blood supplying the placentas. This may contribute to the growth retardation seen in fetal alcohol syndrome.

Tissue antioxidant status in streptozotocin-induced diabetes in rats : effects of dietary manganese deficiency

Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague-Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 wk. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 or 8 wk. The control groups comprised rats not injected with STZ and fed either Mn-deficient or Mn-sufficient diets for a total of 12 wk.The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copperzinc superoxide dismutase (CuZnSOD) in kidney, in the non-diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Plasma and hepatic vitamin E levels increased progressively with the duration of diabetes, independent of dietary Mn intake. Lipid peroxidation, as measured by H2O2-induced production of thiobarbituric acid reactive substances in erythrocytes, also increased, concomitant with decreased liver and kidney glutathione (GSH) levels. These findings demonstrate for the first time an interactive effective between Mn deficiency and STZ-diabetes, resulting in amplification of tissue antioxidant changes seen with either Mn deficiency or STZ-diabetes alone. This effect of Mn deprivation in experimental diabetes suggests a physiological role for Mn as an antioxidant nutrient.

Plasma Amino Acids and Glucose Levels in the Rat Fetus and Dam after Chronic Maternal Alcohol Consumption

To evaluate the effect of chronic maternal alcohol consumption on plasma amino acid and glucose levels in both the fetus and the mother, female Sprague-Dawley rats were divided into 3 dietary treatment groups. Group 1 (alcohol) was fed ad libitum a stock diet plus 20% alcohol in drinking water for at least 4 weeks before mating and 30% alcohol during gestation. Group 2 was pair-fed the stock diet plus corn starch calorically equivalent to the amount of alcohol consumed by group 1 animals. Group 3 (control) received the stock diet and water ad libitum. On day 21 of gestation the fetuses of alcohol-treated dams weighed significantly less than those of the control and pair-fed groups. Fetal plasma glucose levels were significantly lower in the alcohol group when compared to those of the pair-fed and control groups, while the maternal glucose levels were similar in all three treatment groups. Plasma amino acid concentrations showed no corresponding trends in mother and fetus. Only proline was significantly reduced and alpha-amino-n-butyric acid elevated in the alcohol-treated dams when compared to the pair-fed and control rats. In the fetal plasma, only aspartic acid was significantly lower in the alcohol group when compared to the other two groups. A moderate degree of dehydration occurred in the alcohol-treated dams, but plasma albumin was within normal levels. It is concluded that the marked decrease in the concentration of plasma glucose in alcohol-exposed fetuses may be partially responsible for their retarded growth.

Effect of sodium selenite on methylmercury-induced cleft palate in the mouse.

Abstract The effects of simultaneous administration of sodium selenite on the teratogenic action of methylmercury was examined. Methylmercury, or sodium selenite, or a mixture of methylmercury and sodium selenite was administered subcutaneously to pregnant ICR-strain mice on Days 9 through 12 or Days 7 through 12 of gestation, and intraperitoneally to pregnant C57BL-strain mice on Days 7 through 12 of gestation. On Day 17 of gestation the fetuses were removed and examined for cleft palates. Although the incidence of cleft palate in the fetuses, on Day 17, differed according to the concentration of methylmercury (3 or 5 mg/kg/day) and the duration of administration (1 injection per day for 4 or 6 days), the simultaneous administration of selenium at concentrations of 0.0625 to 3.5 mg/kg/day did not reduce the incidence of cleft palate. At the higher concentrations (0.5 to 3.5 mg/kg/day) selenium appeared to increase the maternal toxicity and the teratogenicity of methylmercury. Analysis of fetal body weights on Day 17 of gestation indicated that in those groups in which methylmercury alone resulted in a significant decrease in body weight, the simultaneous administration of selenium did not prevent this growth suppression. It is suggested that cleft palate induction by methylmercury is the result of suppression of growth, rather than a tissue-specific teratogenic action. The effects of methylmercury and selenium on other parameters of maternal and fetal health are also discussed.

Histological Changes in the Placenta Induced by Maternal Alcohol Consumption in the Rat

To investigate the placental enlargement which accompanies maternal alcohol consumption during pregnancy, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On days 17, 18, 19 and 20 of gestation, placentas were removed for histological observation. On days 18-20, the placentas of alcohol-fed rats weighted significantly more than did those of controls, although there was no difference in weight on day 17. Giant cells in the basal zone were significantly increased in number and size in alcohol-fed rats compared to controls. Trophoblastic cells in the basal zone were significantly larger in the alcohol group than in the control groups except on day 17. The maternal blood channels in the labyrinth were wider and more filled with blood corpuscles in the alcohol group than in either control group. It is concluded that the increased weight of the placenta may be largely due to stagnated maternal blood cells in the labyrinthine blood channels and also to the increased number and size of giant cells and the enlarged trophoblastic cells in the basal zone.

Method of ethanol administration as a confounding factor in studies of fetal alcohol syndrome

Female Sprague-Dawley rats were fed a complete liquid diet containing either 5.5% ethanol (mean daily intake of about 9g of ethanol per kg body weight) or an isocaloric amount of dextrose (control group), with additional water available ad libitum. The diets were fed for four weeks prior to and throughout pregnancy. On day 20 of gestation cardiac output and blood flow to the the placenta, heart, kidneys and uterus were measured and plasma osmolality and muscle dry weight were determined. No significant differences were seen between alcohol and control groups with respect to litter size, fetal weight, maternal cardiac output, blood flow to the placenta or other organs, plasma osmolality, or muscle dry weight. This contrasts with previous experiments in which a similar quantity of alcohol (as % calories) was offered in drinking water (equivalent to a mean daily ethanol intake of 10g/kg body weight). Under those conditions fetal weight was reduced, blood flow to the placenta was reduced, and plasma osmolality and muscle dry weight were increased, indicating a moderate degree of dehydration. It is concluded that the effect of ethanol ingestion is influenced by the mode of administration of the ethanol. Dehydration may be a confounding factor in studies of animal models of fetal alcohol syndrome, although it is not possible to rule out a differential metabolic response to alcohol, depending on the mode of administration.

Lactose intolerance in Canadian West Coast Indians

Lactose tolerance tests were performed on 30 healthy Canadian West Coast Indians and 16 non-Indians of Northern European extraction. Among the Indians, there were 7 males and 23 females, aged 14–24 years, with only 1 above 20 years of age (mean 15.8 years). The non-Indians consisted of 3 males and 13 females, aged 15–26 years, with only 2 above 18 years of age (mean 17.4 years). The tests revealed that of the 30 Indians, 19 (63.3%) were lactose intolerant on the basis of maximal blood glucose rise of less than 20 mg/100 ml above the fasting level after the lactose load. Gastrointestinal symptoms during or after the test were observed in 68.4% of the subjects with a flat blood glucose curve and in 18.2% of those with normal curves. In contrast, of the 16 non-Indians, only 1 (6.3%) was lactose intolerant, and none experienced abdominal discomfort during or after the test. Milk consumption among most of the Indian subjects seems to be low by North American standards, as judged by their past milk-drinking habits. The results suggest a high incidence of lactose intolerance among West Coast Indians during adolescence.

Effects of manganese and vitamin E deficiencies on antioxidant enzymes in streptozotocin-diabetic rats

Abstract Vitamin E and manganese deficiencies have been shown independently to affect the capacity to scavenge endogenously produced reactive oxygen species (ROS) in streptozotocin (STZ)-diabetic, Sprague-Dawley rats. Whether combined vitamin E and manganese deficiencies would additively affect oxidative stress was assessed in this study. Plasma and hepatic vitamin E were severely depleted in vitamin E-deficient rats, and susceptibility to lipid peroxidation in kidney, heart, liver, and pancreas tissues was increased, independent of manganese. Activities of key antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase in heart, liver, kidney, and pancreas were altered by manganese and vitamin E deficiencies, although no additive effects were observed. Hemoglobin glycosylation was elevated in vitamin E-deficient, diabetic rats, an effect that further underscores the increased oxidative stress in vitamin E deficiency states.

Does dehydration contribute to retarded fetal growth in rats exposed to alcohol during gestation

An earlier study showed that pregnant rats given ethanol in drinking water exhibited a significant degree of dehydration. The objective of the present study was to determine whether dehydration alone contributes to fetal growth retardation in alcohol treated rats. Female Sprague-Dawley rats were divided into 4 dietary groups. Group 1 (alcohol) received 20% ethanol in drinking water for four weeks prior to mating and 30% alcohol in drinking water throughout pregnancy and a stock diet ad libitum. Group 2 (pair-fed) was given an amount of food equal to that consumed by the alcohol group with the alcohol isocalorically substituted by corn starch. Water was available ad libitum. Group 3 (pair-water) was given an amount of food and water equal to that consumed by the alcohol animals. Group 4 (ad libitum) was given food and water ad libitum. On day 21 of gestation body weights of the alcohol exposed fetuses were significantly lower than those of the other three treatment groups. The difference in fetal body weights between the pair-fed and pair-water groups was not significant. Placentas were significantly heavier in the alcohol group than in the pair-fed and pair-water groups. Maternal plasma osmolality was significantly higher in the alcohol treated rats when compared to the pair-fed and ad libitum controls but not the pair-water group. No significant differences were seen in fetal plasma osmolality among the four treatment groups. It is concluded that dehydration does not contribute significantly to retarded fetal growth in rats given alcohol in drinking water as the sole source of fluid prior to and during gestation.

Interaction of cadmium and zinc during prenatal development in the rat.

Cadmium chloride, zinc chloride, or a mixture of the two, labeled with 115m-Cd or 65-Zn was administered intraperitoneally to Wistar rats on day 9 of gestation. On day 20 fetuses of Cd-treated rats exhibited malformations, but those of rats given zinc or zinc plus cadmium did not. No radioactive cadmium was recovered in the fetuses or fetal membranes, although some was found in the placentas. Simultaneous administration of zinc did not alter the distribution of cadmium, but cadmium significantly increased the amount of zinc in the fetus and placenta. In a second experiment, cadmium or cadmium plus zinc was administered on day 9 of gestation and embryonic units were removed on days 10, 11, and 12. On day 10 cadmium was found in the embryonic unit and maternal uterus, and cadmium in both was significantly reduced by simultaneous administration of zinc. The cadmium concentration in uterus and embryonic units decreased sharply on day 11 and 12 and by day 12 did not differ in animals treated with cadmium or with cadmium plus zinc. It is concluded that cadmium reaches the placenta or embryo at an organogenetically sensitive time, and that zinc may protect the embryo by decreasing the exposure to cadmium this time.