Abstract
Diets high in cholesterol (Ch) have been shown to cause significant elevations in plasma Ch in several animals including man. Elevated plasma Ch has been shown to be an independent risk factor for coronary heart disease.
Consistent features of Ch-induced hypercholesterolemia in several animals are the occurrence of β-VLDL in the d<1.006g/ml fraction, an increase in the IDL and LDL, a decrease in the typical HDL and the appearance of HDLc.
Plasma lipoprotein abnormalities are common in the patients with diabetes mellitus. They are of considerable clinical interest because of the higher incidence of atherosclerosis in the diabetics.
Recently we have found that Ch-fed diabetic rat had marked elevations of plasma Ch and triglyceride (TG) and had higher concentrations of lipoproteins of VLDL (d<1.006g/ml), IDL (1.006<d<1.019g/ml) and LDL (1.019<d<1.063g/ml) as compared with Ch and propylthiouracil (PTU)-fed non-diabetic rat. Insulin treatment was highly effective to improve hyperlipoproteinemia of Ch-fed diabetic rat as well as 17α-ethinyl estradiol treatment.
The present study was designed to investigate the effect of niceritrol (pentaerythritol tetranicotinate) on plasma lipids and plasma lipoproteins of Ch-fed rat, diabetic rat and Ch-fed diabetic rat. Non-diabetic control rats and streptozotocininduced diabetic rats were fed on the diet containing 1% Ch, 1% lard and 0.3% sodium taurocholate
for 4 weeks. In non-diabetic rats, 0.1% PTU was added. Niceritrol-treated rats were fed on the diet containing 0.5% niceritrol. Ch and PTU-fed rats had features of plasma lipoproteins as described previously. Niceritrol treatment significantly decreased the Ch-rich IDL and LDL (IDL-Ch: 189±40.2mg/100ml vs 87±19.9mg/100ml, p<0.01, LDL-Ch: 101±8.6mg/100ml vs 69±4.9mg/100ml, p<0.001). Plasma Ch also decreased, but there was no significant difference as compared with Ch and PTU-fed rats (325±44.4mg/100ml vs 230±27.9mg/100ml). HDL-Ch was significantly increased by niceritrol treatment in Ch and PTU-fed rats (16±3.1mg/100ml vs 53±4.1mg/100ml, p<0.001). Diabetic rats were hypertriglycedemic due to high concentrations of TG-rich lipoproteins (VLDL). Niceritrol treatment significantly decreased the plasma and VLDL TG (plasma TG: 228±35.2mg/100ml vs 103±16.5mg/100ml, p<0.01, VLDL-TG: 211±35.3mg/100ml vs 96±16.3mg/100ml, p<0.05). However, niceritrol did not affect the plasma lipids and plasma lipoproteins in Ch-fed diabetic rats. Since it has been shown that 17α-ethinyl estradiol improves the hyperlipoproteinemia of Ch-fed diabetic rat provably by increasing the number of apo B, E receptor of hepatocytes, it was suggested that niceritrol would not affect the activity of apo B, E receptor in hepatocytes.
