vitamin-d-2 and tanshinone

We have previously proved that oxidized low-density lipoprotein (oxLDL), a proatherogenic lipoprotein, plays a pivotal role in the development of atherosclerotic calcification (AC). The present study was performed to investigate whether tanshinone II A (TS II A), an anti-oxidant which has been shown to inhibit in vitro oxidation of LDL, has the effects to inhibit AC in rat model and by which, if any, mechanisms.. Rat AC model was induced by excessive vitamin D(2) (VD) and high cholesterol diet (HCD), which was proven to be successful histopathologically and biochemically.. Administration of AC rats with TS II A (35, 70 mg/kg) dose-dependently attenuated the AC pathological changes, meanwhile reduced the vessel contents of lipid and calcium. However, TS II A had no effects on serum levels of lipids, calcium and 25-OH VD. Further studies revealed that TS II A decreased serum concentration of oxLDL, reduced the superoxide anion production and malondialdehyde (MDA) in vessel. In addition, TS II A increased vessel Cu/Zn SOD activity, upregulated vessel mRNA and protein expression of Cu/Zn SOD.. The results suggested that TS II A significantly attenuated the AC in rat model, which might be attributed to its inhibition of oxLDL production independent of the serum levels of lipids, calcium and 25-OH VD, and that increasing of Cu/Zn SOD activity as well as mRNA and protein expression by TS II A might protect LDL against oxidation induced by superoxide anion in vessel.

Topics: Abietanes; Animals; Antioxidants; Aorta, Thoracic; Atherosclerosis; Calcinosis; Calcium; Cholesterol; Cholesterol, Dietary; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Induction; Ergocalciferols; Lipoproteins, LDL; Male; Malondialdehyde; Oxidative Stress; Phenanthrenes; Rats; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase; Superoxides; Time Factors