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.