[Therapeutic effect of Olea europea var. oleaster leaves on carbohydrate and lipid metabolism in obese and prediabetic sand rats (Psammomys obesus)]. / Effet thérapeutique des feuilles d'Olea europea var. oleaster sur le métabolisme glucido-lipidique chez le rat des sables (Psammomys obesus) obèse prédiabétique.

Sand rats develop obesity, insulin-resistance, hyperlipidemia and prediabetes, when given a standard laboratory chow diet. We have used this model to demonstrate the beneficial action of olea europea var. oleaster leaves to regulate unbalanced metabolism. 32 sand rats fed on hypercaloric diet during 7 months, were divided into 3 groups: controls (n=10), treated by plant (n=13) and treated by simvastatin (Zoco); hypocholesterolemic drug. The plant decoction prepared at 10% was given orally at the rate of 1.5 ml/100g during 3 months. Results show that the plant presents a hypocholesterolemic effect (42%) related to decreases in LDL and VLDL cholesterol. In addition, hypoglycemic (16%) and antihyperglycemic (40%) effects were observed accompanied by a 27% decrease in insulin. Chronic treatment with Zocor reduced total cholesterol (32%), LDL and VLDL cholesterol. Both of treatments produced no significantly reduction in plasma levels of triglycerides and HDL cholesterol. No noxions effect of this plant have been observed in usual doses.

New model of atherosclerosis in insulin resistant sand rats: hypercholesterolemia combined with D2 vitamin.

To overcome the sand rats' resistance to cholesterol induced atherosclerosis, animals were given D2 vitamin at 2000 IU/rat per day associated with cholesterol-enriched diet for 45 days, following 45 days of high cholesterol diet alone. At days 0, 45 and 90, plasma parameters, aortic and heart morphology were examined. Other animals receiving a high cholesterol diet alone were used as a control group. Results showed at day 45 severe hypercholesterolemia, elevated plasma LDL and VLDL-cholesterol, oxidized LDL and calcium levels, a rise of lecithin cholesterol acyl transferase activity and moderate hyperinsulinemia. Lesions were characterized by widening of the first interlamellar spaces in the aorta, fibrosis of coronary arterial wall and recent foci of myocardial fibrosis. At day 90, plasma calcium level decreased and oxidized LDL were more enhanced. Insulin resistance development was associated with glucose intolerance and hyperinsulinemia. The D2 vitamin administration induced advanced atherosclerotic lesions in arterial wall, represented by the rupture of elastic lamellae, smooth muscle cell proliferation and lipid-calcic core. The complicated plaque frequently evolved into ulcerations. The ischaemic effects were represented by acute myocardial infarction. D2 vitamin is an atherogenic agent which, when associated with hypercholesterolemia, allows the development of advanced atherosclerotic lesions in sand rat which resembles human plaque.

New model of atherosclerosis in sand rats subjected to a high cholesterol diet and vitamin D2.

In order to defeat the atheroresistance in sand rats, 25 animals were given a high cholesterol diet for 45 days, which was then associated with oral treatment with vitamin D2 2000 IU/day for a further 45 days. At days 0, 45 and 90, plasma parameters, and aortic and heart morphology were examined. Results showed at D45 hypercholesterolaemia, increased plasma LDL and VLDL cholesterol, oxidized LDL, triglycerides, free fatty acids (FFA) and calcium levels and moderate hyperinsulinaemia. At D90, plasma-oxidized LDL and FFA were more enhanced, whereas calcium level was reduced. Development of hyperglycaemia was associated with hyperinsulinaemia and insulin resistance. The vitamin D2 administration induced advanced lesions, represented by the degenerescence of elastic lamina, smooth muscle cell proliferation and lipid calcic plaque at an ulcerated stage in most cases. The ischaemic effects were represented by acute myocardial infarction. The potential of the sand rat to develop atherosclerotic lesions at different stages opens the field to therapeutic tests of new anti-atherogenic agents.

Effect of Suaeda fruticosa aqueous extract in the hypercholesterolaemic and insulin-resistant sand rat.

To study the effect of Suaeda fruticosa in lipid and carbohydrate metabolism in the hypercholesterolaemic and insulin resistant sand rat, 25 rats were subjected to a high cholesterol diet for 90 days. On the 45th day the animals were divided into two groups: control and treated. Aqueous extract prepared in infusion at 10 per cent was administered orally at 1.5 ml per 100 g of body weight per day. On the 90th day, the control group developed a severe hyperlipidaemia, impaired glucose tolerance test and insulin resistance. Treatment by Suaeda fruticosa extract showed hypoglycaemic (41 per cent) and antihyperglycaemic (53 per cent) effects. Furthermore, the plant led to a decrease in plasma levels of insulin (31 per cent), total cholesterol (50 per cent), LDL cholesterol (55 per cent), VLDL cholesterol (49 per cent), oxidized LDL (40 per cent), lecithin cholesterol acyl transferase (44 per cent), triglycerides (57 per cent) and free fatty acids (36 per cent). We concluded that Suaeda fruticosa aqueous extract contains at least two compounds responsible for hypoglycaemic and hypolipidaemic activities.

Effects of Olea europea var. oleaster leaves in hypercholesterolemic insulin-resistant sand rats.

Sand rats fed a hypercaloric diet manifest obesity and diabetes. We have used this model to develop hypercholesterolaemia and describe the beneficial action of Olea europea var. oleaster leaves. Twenty-eight sand rats submitted to a high cholesterol diet for four months were assigned to control and treated groups. Plant decoction at 10 per cent was given orally for two months. Results showed that the control group exhibited hyperglycaemia, glucose intolerance, hypercholesterolaemia and moderate hyperinsulinaemia. Light microscopic study showed thickening of capillary walls in skin, pancreas and kidney. The treatment produced hypoglycaemic (43 per cent, p < 0.001), antihyperglycaemic (48 per cent, p < 0.001) and hypoinsulinaemic (39 per cent, p < 0.01) activities. In addition, the plant presented a hypocholesterolaemic effect (47 per cent, p < 0.001) accompanied by lowering of oxidized LDL (30 per cent, p < 0.01). Accordingly, capillary wall thickening was reduced in skin and pancreas and completely prevented in kidney. The data demonstrate that oleaster leaves possess at least two active compounds to treat hypercholesterolaemia and diabetes.