PHYSIOLOGICAL ACTIVITIES OF ORGANIC GERMA NIUM COMPOUNDS REGULATION OF THE MAILLARD REACTION BY ORGANIC GERMANIUM COMPOUNDS

Organic germanium compounds [bis (2-carboxyethylgermanium) trioxide: G e-132, bis 2-amino-2-carboxy-1-phenylethylgermanium)trioxide: Ge-373, bis(2-amino-2-carboxyethylgermanium) trioxide: Ge-385] were found effe ctive in suppressing the formation of Advanced Glycation Endproducts ( AGE) from serum proteins, collagen and lens crystallin. We examined th e Maillard reaction between amino acids and ribose, and the effects of organic Ge-compounds on the reaction. Ge-compounds did not prevent th e formation of Amadori-rearranged substances(ARS), but inhibited furth er progress toward AGE formation. Specifically, Ge-385 caused the decr ease in AGE after incubating the mixtures for longer than 10 days. The mode of action of Ge-compounds in the Maillard reaction was investiga ted by a NMR to clarify the interaction between glucose and organic Ge -compounds. These compounds could conjugate glucose directly through h ydroxyl residues of glucose at the sites 1 and 2. The glucose Ge-compo und complexes might result in the disconnection of amino-carbonyl prod ucts to glucosone and amino residues. Organic germanium compound, spec ifically Ge-385, which has two amino residues in its one molecule, app ears to be much more effective than Ge-132 in the prevention of AGE fo rmation by making carbonyl-NH2-(Ge-385) conjugates as the substitute o f reactive amino residues on functional polypeptides. The effects of o rganic Ge-compounds were examined in DM-rats induced by streptozotocin (STZ). Both drugs, Ge-132 and 385, were respectively administered to STZ-DM-rats via per oral rout, and clinico-pathological examinations r evealed that the formation of glycated serum albumin, serum fructosami ne, and cataract (turbidity of lens) were remarkably improved. Ge-comp ounds are the first candidates that prevent and reversibly solubilize the Maillard products which induce severe clinical complications in pa tients with diabetes mellitus