Policosanol as a new inhibitor candidate for vascular calcification in diabetic hyperlipidemic rats

Abstract

This work mainly aimed to investigate the probable changes of aortic calcification by policosanol, omega-3 fatty acids in comparison with atorvastatin and subsequent progression of atherosclerosis in diabetic hyperlipemic rat model. Adult male albino rats of wistar strain (30) were divided into five groups (n = 6/group); one was fed normal diet and was used as a normal group, the other groups received alloxan, atherogenic diet (CCT - rat chow diet supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) and categorized as follows: the second group received no treatment and kept as control (diabetic hyperlipidemic control group (DHC)). The other groups received daily oral doses of atorvastatin, policosanol (10 mg/kg body weight) and ω-3 (50 mg/kg body weight), respectively, for eight weeks. Different biomarkers were used for the evaluation that included inflammatory (C reactive protein (CRP), tumor necrosis factor α (TNF-α)), oxidative stress (glutathione (GSH), malondialdehyde (MDA)) bone calcification markers (alkaline phosphatase (ALP), Vitamin D, parathyroid hormone (PTH)), lipogram pattern in addition to histochemical demonstration of calcium in the aorta. Diabetic hyperlipemic group demonstrated significant hyperglycemia, hyperlipidemia, and increased inflammation, oxidative stress, calcification, and finally atherogenesis progression. Treatment of diabetic hyperlipemic rats with, policosanol, omega-3 fatty acids (natural products) and atorvastatin for eight weeks significantly increased high-density lipoprotein cholesterol (HDL-C), Vitamin D, decreased aortic vacuoles number, and inhibited calcification process. Policosanol induced more remarkable reduction in the density and number of foam cells and improved the intimal lesions of the aorta as compared to atorvastatin. Drugs under study exerted hypoglycemic effect along with an inhibition of inflammation, oxidative stress, and calcium deposition with certain variations but policosanol effect was remarkable in comparison with other drugs.

Keywords: Diabetic hyperlipidemia; aortic calcification; atorvastatin; inflammation; omega-3 fatty acids; oxidative stress; policosanol.

Figure 1

Effect of policosanol on blood glucose level. (#p < 0.001) NG vs DHC, (*p < 0.001) DHC vs. treated groups, (cp < 0.001) ATOR vs ω-3, PC, (++p < 0.001) ω-3 vs PC. (A color version of this figure is available in the online journal.)

Figure 2

((a) and (b)) Photomicrograph of normal aorta, (a) (H&E × 150), (b) (H&E × 200). (c) Aorta of DHC rats illustrated large lipid vacuoles or foam cells (*stars) in the cells of tunica intimae (TI), tunica media (TM) with ulceration of the intimal endothelial cells and loose tunica adventitia (TA) (H&E × 200). (d) Aorta of ATOR-treated rats (H&E × 200). (f) Aorta of ω-3 treated-rats (H&E × 200). (e) Aorta of PC-treated rats (H & E × 200). (A color version of this figure is available in the online journal.)

Figure 3

Correlation between HDL-C, TNF-α, GSH with calcification markers (ALP, VIT.D, PTH). (A color version of this figure is available in the online journal.)

Figure 4

Alizarin red staining of the aorta: (a) normal aorta of NG rats, (b) aorta of DH-rats, (c) aorta of ATOR-treated rats, (d) aorta of ω-3-treated rats and (e) aorta of PC-treated-rats. (A color version of this figure is available in the online journal.)