High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE(-/-) mice.

Homocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE(-/-) mice fed high-methionine diet for 20weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The up-regulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis.

A 4-week toxicity study of methionine in male rats.

To examine 4-week toxicity of l-methionine (methionine), 5-week-old Fisher strain male rats were fed on diets containing 0, 0.1, 0.3, 0.9, 2.7 (w/w) of added methionine. Although no deaths were recorded, the highest dose of methionine (2.7% [w/w] of diet) reduced food intake and significantly suppressed growth rate. Growth suppression was characterized by an increase in hemolysis, splenic, and hepatic accumulation of hemosiderin, hemolytic anemia, and promotion of hematopoiesis. Other changes observed in the highest methionine intake group were a decrease in white blood cell count, thymus atrophy, and histological abnormalities in the adrenal gland and testis. Small, but significant, growth suppression, accompanied by some minor changes in plasma biochemical parameters, was also seen in rats fed on a test diet containing 0.9% (w/w) of additional methionine. Thus, no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of diet-added methionine were determined at 0.3% and 0.9% (w/w), corresponding to 236 and 705 mg/kg/d body weight, respectively. Since the basal diet contained protein-bound methionine at 0.5% (w/w), NOAEL and LOAEL of total dietary methionine were estimated at 0.8% and 1.4% (w/w) of diet.

Overingestion of methionine tablets by a dog.

Methionine tablets are used as urinary acidifiers for pets and to decrease damage from dog urine to lawns. A 39-kg Labrador Retriever ingested approximately 350 tablets containing 150 mg methionine/tablet and was presented after repeated episodes of vomiting. The only abnormality was posterior ataxia suggestive of spinal cord injury. The animal was treated with i.v. fluids, steroids and gastrointestinal protectants. Approximately 4.5 h after entering the clinic the dog had a single seizure episode lasting 2-3 min which was treated with phenobarbital. Serum ammonia at that time was normal (0.19 mg/dL). The animal did not show further CNS abnormalities and awoke apparently normal. A musty odor to the breath was noticed through the course of the day, possibly due to volatile mercaptans produced from methionine metabolism. The animal made an uneventful recovery and was discharged the next day.

[Effect of vitamin B1 and vitamin E on methionine poisoning in broiler chickens]. / Vliianie na vitamin B1 i vitamin E pri metioninova intoksikatsiia u pileta broileri.

An experiment was carried out with 100 broiler birds of the Leghorn breed, aged 20 days. The birds were divided into groups and were given various amounts of methionine--0,5, 2, and 3 per cent with the basic standard mixture. The clinical signs of methionine intoxication were followed up--drowsiness, weakness in the legs, opisthotonus, and twisting of the neck (torticollis) alons with the loss of equilibrium. It was found that with birds receiving 0.5 per cent methionine with the diet the amount of vitamins A, E, and B1 in the blood serum and the liver rose considerably, while with birds given 2 and 3 per cent methionine with the feed the amount of these vitamins dropped essentially. Therepeutic treatment with 3 mg of vitamin E and vitamin B1 each in the course of 4 to 6 days yielded a good effect. An improvement of the general condition and disappearance of the most typical symptoms of methionine intoxication were recorded.

[Effect of varying amounts of methionine on chickens]. / Vurkhu vliianieto na razlichni kolichestva metionin pri pileta.

The effect of high methionine quantities on chickens was studied. The experiment was carried out with hundred 20-day old chicken-broilers, divided in four groups. A positive effect of 0.5% methionine added to the main ration was recorded. It resulted in 1109 g gain in weight as compared to 819,1 g for the control group. Two and three percent of methionine reduced the gain with 52.49 and 44.13% respectively. Toxic reactions were observed in II and III groups. Lethality in these groups reached 30 and 60% respectively. Haemoglobin content was considerably reduced, while blood sugar, carotene and vitamin A contents increased proportionally to the methionin quantities introduced in the ration. No significant changes in the values of serum calcium, phosphorus, magnesium and SGOT, SGPT activity before and after the experiment were established.

Intestinal absorption rate of L-methionine in man and the effect of glucose in the perfusing fluid.

1. Using a double-lumen tube perfusion system the rates of absorption of L-methionine and glucose from a 30 cm segment of the jejunum were estimated in eight relatively normal Zambian African subjects. The effect of each substrate on the absorption of the other has also been investigated. The solutions perfused were given at 12.0 ml. min(-1), and contained (A) 100 m-mole l.(-1)L-methionine, (B) 100 m-mole l.(-1)L-methionine and 150 m-mole l.(-1) glucose and (C) 150 m-mole l.(-1) glucose.2. The presence of glucose in the perfusing fluid did not significantly alter the mean absorption rate of methionine; in six subjects, the rate of methionine absorption from solution B was less than from solution A, but in two there was a marked difference in the opposite direction. This may indicate an individual difference in the effect of glucose on L-methionine absorption in man. The presence of methionine in the perfusing fluid did not significantly alter the mean absorption rate of glucose.3. Five subjects had a transitory psychiatric disturbance after the investigation. The cause of this is not clear, but was probably caused by the absorption of a break-down product of methionine from the large intestine.