Joan R. Weyant

Vitamin e, cholesterol, and lipids during atherogenesis in rabbits.

Rabbits were fed diets including cholesterol and 10% butterfat to determine whether polyunsaturated butter (9% 18∶2) would be less atherogenic than normal saturated butter (3% 18∶2) when fed for 12 weeks. The cholesterol diets alone, 0.5% or 2%, produced aortic plaque development, and plasma cholesterol increased 20 times, lipids increased 10 times, and vitamin E increased 5 times. The inclusion of both fat and cholesterol in the diet produced a synergistic effect, doubling these values to 40 times for cholesterol, 20 times for lipids, and 10 times for vitamin E. The higher circulating levels of cholesterol caused increased tissue levels of cholesterol. With 2% cholesterol and fat, liver and aorta cholesterol increased 10 times, heart 4 times, and muscle cholesterol 2 times. The lower 0.5% dietary cholesterol load was successful in limiting the amount of tissue cholesterol increase. Liver, aorta, heart, and muscle levels of cholesterol were only about half the concentration attained when 2% cholesterol was fed. It was concluded that there were no differences in plasma or tissue cholesterol, vitamin E, or atherosclerosis attributable to the polyunsaturated nature of the diet. The 10% butterfat diets alone, whether saturated or unsaturated, did not induce aortic plaques and did not increase blood or tissue cholesterol, lipids, or vitamin E. Our results suggest that the lipid mobilizing effect is mediated by cholesterol, probably by conversion to bile acids and a stimulation in intestinal absorption.

Effect of several dietary levels of o,p′-DDT on reproduction and lactation in the rat

ConclusionsThe levels of o,p′-DDT fed in this experiment were considerably above those likely to be encountered in accidental feed adulteration or through careless use of the insecticide. Even though these experiments included the critical periods of reproductive maturation and were extended through two pregnancies, no adverse effect on female reproduction could be determined. Since o,p′-DDT is the most estrogenically potent of the isomers or metabolic analogs of DDT, these experiments serve to indicate levels of exposure that can be safely tolerated throughout growth, pregnancy, and lactation. Further, since technical DDT contains only 15–20% of the o,p′-isomer, by extrapolation it would be expected that daily amounts as high as 1 gram of the technical insecticide preparation (80–85%, p,p′-DDT) could be ingested without deleterious effects on reproduction, except for the physiological effects of so large a dose.As judged from these experiments on a small laboratory rodent, our results indicate that o,p′-DDT, an estrogenically active pesticide, does not adversely affect reproduction in mammals.

Reduction of blood and liver cholesterol in the rat by straight and branched chain alkyl amines

The activities of a branched chain and several straight chain amines (C12 to C18 chain length), and the azasteroid 25-aza-5α-cholestane were compared with those of 20,25-diazacholesterol dihydrochloride, which is a potent hypocholesterolemic agent in the rat. These amines and azasteroids inhibit the Δ24-sterol reductase system in the tobacco hornworm,Manduca sexta (L.), and also block the conversion of C28 and C29 plant sterols to cholesterol, with a resulting accumulation of desmosterol. The effects of these compounds in the rat were determined on body weight gain, cholesterol, desmosterol, and lipid composition of blood, feces, liver, and epididymal fat pad weight. The two azasteroids and the branched chain amine, N,N-dimethyl-3, 7,11-trimethyldodecanamine, had the greatest effect, reducing total plasma lipids and plasma sterols to approximately 40–50% of the levels in control rats and produced a concomitant increase in plasma and liver desmosterol. The branched chain dodecanamine caused a reduction in both feed consumption and body weight gain. The branched and straight chain dodecanamines also severely reduced epididymal fat pad weight. Our results demonstrate that the simple azasteroid, 25-aza-5α-cholestane, is a more potent inhibitor of cholesterol biosynthesis than the diazasterol and that the Δ24-sterol reductase system in a mammal can be inhibited by simple, nonsteroidal, acyclic amines.

Antifertility action of IUDs inserted in rats after mating

Abstract Monofilament nylon, double S-shaped IUDs were inserted through the cervical os into one uterine horn of rats on days 1–6 following mating. Other rats were similarly treated with sham insertions. Examination of uteri on day 18, 19 or 20 following mating revealed that placement of an IUD was contraceptively effective on all days through day 5, the time implantation normally occurs. The procedure was least effective in preventing implantation when inserted on day 1. The insertion of the empty applicator did not cause reduction in the number of pregnancies if inserted early in gestation, but caused reduction in the number of horns containing pregnancies on days 4 and 5. Both horns receiving IUDs and sham treatments on days 4 and 5 showed a high incidence of deciduoma development. Untreated contralateral control horns in both series, IUD and sham insertions, had equal numbers of live fetuses at 18–20 days, indicating that the IUD did not increase embryonic death in these horns. The experiment provides evidence that IUD action to prevent implantation requires only 2 days at most to become effective.

Stimulation of lipid absorption in young rats by cholesterol: Early time changes and effects on pentobarbital sleeping time

Four groups of young male and female rats were fed a chow diet (0), chow plus 10% corn oil (F), chow plus 1% cholesterol (C), or chow plus 1% cholesterol plus 10% corn oil (CF) for 1, 2, 4 and 8 days. After 2 dats, male F, C and CF rats exhibited a shorter anesthesia period (−20 to −30%) when given pentobarbital. By 4 days, male F and C rats had pentobarbital sleeping times (PB-ST) 20% less than 0 rats. These effects were additive and CF rats had 40% shorter PB-ST. Reduction of PB-ST by cholesterol and corn oil was similar but slightly less in female rats. Liver lipid content doubled in 4 days in CF rats, and liver cholesterol was 4 times that of 0 rats. These changes and the increases in metabolism of barbiturate suggested changes in liver microsomal enzyme activities. Serum glutamic oxaloacetic and glutamic pyruvic transaminase, two enzymes reflective of liver damage, did not increase after 8 days on C, F or CF diets. Our results suggest that consumption of an animal sterol and a high lipid diet by laboratory rats, normally consuming a diet low in fat (3–4%), increases the ability of the animal to detoxify a barbiturate. Storage of absorbed dietary cholesterol in the liver may represent a major mechanism for maintaining extra hepatic cholesterol homeostasis.

Necessity of vitamin B12 for growth of rats fed on an odd- or even-carbon-number fat.

1. The effect of vitamin B12 on growth was studied in young male and female rats fed on diets sufficient (+B12) or deficient (-B12) in vitamin B12 containing 30% of the dietary energy as fat, either maize oil (CO) or triundecanoin (TUD). 2. Vitamin B12 deficiency severely depressed growth. After 6 weeks the weight gain of CO(-B12) rats was only 72% of that of CO(+B12) rats and the gain of TUD(-B12) rats was only 47% of TUD(+B12) rats. 3. After fasting 24 or 96 h TUD-fed rats, both +B12 and -B12, had greater glycogen reserves and higher plasma glucose levels than CO-fed rats. 4. It is concluded that vitamin B12 is required for the metabolism and utilization of both an odd-carbon-number medium-chain fat, TUD, and an even-C-number long-chain fat, CO, during growth in rats.