Debons A F, Fani K, Jimenez F A, Maayan M L
Nuclear Medicine Service, Veterans Administration, Medical Center, Brooklyn, New York.
J Pharmacol Exp Ther. 1987 Nov;243(2):745-57.
The effect of dimethyl sulfoxide (DMSO) on cholesterol-induced atherosclerosis in the rabbit was investigated. Two groups of rabbits were studied: a Control group which received regular chow and an Experimental group which received an atherogenic diet containing 1% cholesterol. DMSO was either omitted or added to the drinking water of both groups in amounts of 2, 4, 5 and 6%. After 3 months all animals were autopsied; the thoracic aorta was examined for atheromatous lesions and the abdominal aorta assayed for total cholesterol content. As expected the thoracic aortas of all rabbits in the Control group were free of atheromatous lesions. With the exception of one rabbit in the Experimental group, all rabbits on the atherogenic diet which did not receive DMSO had extensive aortic lesions covering 82 +/- 5% of the surface area of the thoracic aorta. Aortic lesions were inhibited by about 50% in rabbits on 2% (dose, 1.5 g/kg) DMSO and virtually absent in the majority of rabbits on 4 (dose, 3.5 g/kg), 5 (dose, 5.5 g/kg) and 6% (dose, 9.1 g/kg) DMSO. The food intake of rabbits on the atherogenic diet was not suppressed by DMSO. Changes in the cholesterol content of the abdominal aortas paralleled the presence or absence of lesions in the thoracic aorta. Blood cholesterol levels were greatly elevated in all rabbits on the atherogenic diet and not lowered by DMSO. In conclusion, cholesterol induced atherosclerosis in the rabbit was inhibited by DMSO. This action of DMSO was independent of the hypercholesterolemia and not due to a suppression of food intake. DMSO may provide a useful probe for investigating the underlying mechanism(s) in the development of cholesterol induced atherosclerosis.
研究了二甲基亚砜(DMSO)对兔胆固醇诱导动脉粥样硬化的影响。研究了两组兔子:一组为对照组,给予常规饲料;另一组为实验组,给予含1%胆固醇的致动脉粥样化饮食。两组兔子的饮用水中均省略或添加了DMSO,添加量分别为2%、4%、5%和6%。3个月后对所有动物进行解剖;检查胸主动脉的动脉粥样病变,并测定腹主动脉的总胆固醇含量。正如预期的那样,对照组所有兔子的胸主动脉均无动脉粥样病变。在实验组中,除一只兔子外,所有未接受DMSO的致动脉粥样化饮食兔子的主动脉均有广泛病变,覆盖胸主动脉表面积的82±5%。服用2%(剂量1.5 g/kg)DMSO的兔子,其主动脉病变受到约50%的抑制,而服用4%(剂量3.5 g/kg)、5%(剂量5.5 g/kg)和6%(剂量9.1 g/kg)DMSO的大多数兔子几乎没有病变。致动脉粥样化饮食兔子的食物摄入量未被DMSO抑制。腹主动脉胆固醇含量的变化与胸主动脉病变的有无平行。所有致动脉粥样化饮食兔子的血胆固醇水平均大幅升高,且未被DMSO降低。总之,DMSO可抑制兔胆固醇诱导的动脉粥样硬化。DMSO的这种作用与高胆固醇血症无关,也不是由于食物摄入量的抑制。DMSO可能为研究胆固醇诱导动脉粥样硬化发生的潜在机制提供有用的探针。