title: Dietary eritadenine suppresses guanidinoacetic Acid-induced hyperhomocysteinemia in rats.
abstract: 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.
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Shizuoka, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Fukada
authors.forename: Minoru
authors.initials: M
authors.lastname: Setoue
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morita
authors.forename: Kimio
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D004032:Diet; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: C100029:eritadenine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; C004946:glycocyamine; D000225:Adenine; D005998:Glycine