ミネラル偏食老齢ラットにおける塩酸bifemelaneの抗動脈硬化作用

Abstract

The reduction of calcium (Ca) intake leads to calcium and magnesium (Mg) being mobilized from the bone pool, and to Ca deposition in the soft tissues, including the central nervous system (CNS). Mg plays a pivotal role as an enzyme cofactor and in the maintenance of the membrane;the role of Mg in membrane physiology permits it to stabilize the electrochemical equilibrium of the membrane by regulating the movement of sodium, potassium, phosphorus and Ca;Mg also plays a major role in the uptake, storage, and release of central or peripheral neurotransmitters. Its role in relation to achieving blockade of the L-type voltage-gated Ca++ channel is also discussed. Mg++ produces a well-characterized voltage-dependent block of the open N-methyl-D-aspartate receptor-gated channel and also reduces Ca channel opening.On the other hand, it has been reported that 4-(obenzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride) possibly participates in activating the cerebral metabolism and in keeping an adequate Mg level in the CNS and soft tissues and is also implicated in metal metabolism in the tissues of rats fed low-Ca diets. In general, bifemelane has a tendency to decrease Ca deposition in the CNS and soft tissues of rats fed low-Ca diets.This study investigated the action of bifemelane hydro-chloride on atherosclerosis in aged rats fed low-Ca diets, and investigated preventive effects of bifemelane hydro-chloride on their atherosclerosis. Twenty-seven male, 18 month-old Wister rats were maintained for 90 days on the following diets: (A) standard diet (n=7), (B) low Ca-Mg+Al diet (n=8), (C) standard diet+forced oral administration of 10mg bifemelane hydrochloride/kg/day (n=6), (D) low-Ca-Mg+Al diet+forced oral administration of 10mg bifemelane hydrochloride/kg/day (n=6). All groups were fed and given deionized distilled water (d. d. w.) ad libitum for 90 days. After the experimental period, blood samples were taken from the abdominal aorta and evaluated for Ca, Mg, Zn, Al, in-P, cholesterol, GOT, GPT, LDH, ChE, CPK, and BUN under sodium pentobarbital. Neither the A-C groups' nor the B-D groups' blood chemistry changed. However, the atherosclerotic effects on groups C and D were remarkably ameliorated, in comparison with those on groups A and B.It seems that bifemelane hydrochloride has a preventive effect on atherosclerosis caused by Ca deposition in the arteries of rats fed low-Ca diets, due to its effect in maintaining Mg and Ca in bones.