We assessed the effect of eritadenine, a hypocholesterolemic factor isolated from the edible mushroom Lentinus edodes, on plasma homocysteine concentration using methyl-group acceptor-induced hyperhomocysteinemic rats. Male Wistar rats were fed a control diet or diets supplemented with a methyl-group acceptor or a precursor of methyl-group acceptor. Diets were supplemented with guanidinoacetic acid (GAA) at 2.5, 5, 7.5, and 10 g/kg, nicotinic acid (NiA) or ethanolamine (EA) at 5 and 10 g/kg, or glycine at 25 and 50 g/kg, and the rats were fed for 10 d (Expt. 1). Plasma total homocysteine concentration was increased 255 and 421% by 5 and 10 g/kg GAA, respectively, and 39 and 58% by 5 and 10 g/kg NiA, respectively, but not by EA or glycine. GAA supplementation dose-dependently decreased the hepatic S-adenosylmethionine (SAM) concentration and the activity of cystathionine beta-synthase (CBS) and increased the hepatic S-adenosylhomocysteine (SAH) and homocysteine concentrations. In another study in which rats were fed 5 g/kg GAA-supplemented diet for 1-10 d, plasma homocysteine and the other variables affected in Expt. 1 were affected in rats fed the GAA-supplemented diet (Expt. 2). We investigated the effect of supplementation of 5 g/kg GAA-supplemented diet with eritadenine (50 mg/kg) on plasma homocysteine concentration (Expt. 3). Eritadenine supplementation significantly suppressed the GAA-induced increase in plasma homocysteine concentration. Eritadenine also restored the decreased SAM concentration and CBS activity in the liver, whereas it further increased hepatic SAH concentration, suggesting that eritadenine might elicit its effect by both slowing homocysteine production and increasing cystathionine formation. The results confirm that GAA is a useful compound to induce experimental hyperhomocysteinemia and indicate that eritadenine can effectively counteract the hyperhomocysteinemic effect of GAA.

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Summary To clarify the relationship between dietary choline level and plasma homocysteine concentration, the effects of choline deprivation on plasma homocysteine concentration and related variables were investigated in rats fed a standard (25%) casein (25C) diet or standard soybean protein (25S) diet. Using the 25S diet, the time-dependent effect of choline deprivation and the comparative effects of three kinds of lipotropes were also investigated. Feeding rats with the choline-deprived 25S diet for 10 d significantly increased plasma total homocysteine concentration to a level 2.68-times higher than that of the control group, whereas choline deprivation had no effect in rats fed the 25C diet. Increases in hepatic Sadenosylhomocysteine and homocysteine concentrations, decreases in hepatic betaine concentration and the activity of cystathionine ␤ -synthase, but not betaine-homocysteine Smethyltransferase, and fatty liver also occurred in rats fed the choline-deprived 25S diet. Plasma homocysteine concentration increased when rats were fed the choline-deprived 25S diet for only 3 d, and the increase persisted up to 20 d. The hyperhomocysteinemia induced by choline deprivation was effectively suppressed by betaine or methionine supplementation. Choline deprivation caused hyperhomocysteinemia also in rats fed a choline-deprived low (10%) casein diet. The results indicate that choline deprivation can easily induce prominent hyperhomocysteinemia when rats are fed relatively low methionine diets such as a standard soybean protein diet and low casein diet, possibly through the suppression of homocysteine removal by both remethylation and cystathionine formation. This hyperhomocysteinemia might be a useful model for investigating the role of betaine in the regulation of plasma homocysteine concentration.