Influence of Theobromine Magnesium Oleate on Formation of Experimental Atheroma 1

Abstract

Summary

Forty-five rabbits were fed an atherogenic diet for three months. One group (23 rabbits) received theobromine magnesium oleate (TMO) orally in two equal doses daily (60 mg/kg/day). The control group received a placebo. Plasma cholesterol levels were determined at 0, 1, 2, and 3 months after the rabbits were placed on the atherogenic diet. At the end of three months the animals were sacrificed, their aortas excised and stained for lipids, and the degree of atherosclerosis estimated by two methods; visual grading of per cent of aortic intima covered by lipid and spectrophotometic determination of the quantity of Sudan IV dye extracted from individual aortas.

The experimental group receiving TMO showed less atherosclerosis than did the control group. The mean per cent of aortic intimal area covered by lipid, based on an average of three independent visual estimates was 66.1 for the experimental group as opposed to 77.8 for the control group. The mean quantity of extracted Sudan IV in milligrams per gram dry weight of aorta for the experimental group was 2.62 and for the control group, 3.64 (p < 0.01). The atherogenic diet increased the plasma total cholesterol in both groups of animals and for the first month the mean values were similar in both groups but by the end of the second month the group receiving TMO showed a lower level of plasma cholesterol. This difference between the two groups increased by the end of the three month study and was statistically significant (p < 0.05) at that time.

These results have been interpreted as evidence that TMO is capable of impeding atherogenesis. Exactly how this is accomplished is unclear. TMO, through inhibition of phosphodiesterase, could lead to increased levels of cyclic AMP which would activate lipase in either the arterial wall, adipose tissue, or liver. Activation of lipase at one or more of these sites could possibly explain the influence of TMO upon the atherogenic process. Further studies in other species and studies to investigate the possibility of direct activation of arterial lipolytic enzymes by TMO are in progress.