Therapeutic Impacts of Tocotrienols and Lovastatin against Diabetic Dyslipidemia in a Rat Model

Introduction: Diabetic subjects are at an increased risk for developing Coronary Heart Disease (CHD), in part because of enhanced oxidation of low- density lipoproteins (LDL), which promotes atherogenesis. It is possible that increased atherogenecity of LDL during diabetes is associated with a preponderance of small dense (sd)-LDL subpopulation, that is more prone to oxidative modification than large buoyant (lb)-LDL. Materials and Methods: In this study, we have investigated the hypolipidemic and antioxidant properties of dietary tocotrienols (Tocomin) and Lovastatin in diabetic-hyperlipidemic rats. In order to induce experimental diabetes, 28 overnight fasted rats were injected with streptozotocin (STZ), (freshly dissolved in 10 mM citrate buffer, pH 4.5, 6.0 mg/100 g body wt) intraperitonially. Results: After 14 weeks of treatment with 6.0 mg Tocomin or 0.50 mg Lovastatin, diabetic control rats had a significant increase in plasma glucose and blood HbA1c, plasma TG, TC, VLDL-C, LDL-C, atherogenic non-HDL-C, while significant reduction in HDL-C, HDL2-C, HDL3-C. Tocomin and Lovastatin mediated a substantial decline in plasma and lipoprotein lipids without any significant change in plasma glucose, HbA1c and HDL-C, HDL2-C, HDL3-C, levels. Diabetes markedly increased the cholesterol and apoB content of sd- LDL including their percent share of LDL, which were significantly reduced in Tocomin or Lovastatin treated rats. Conclusion: In the present investigation we have shown that the treatment of chronic diabetic rats with Tocomin or Lovastatin mediated a decline in blood glucose and HbA1 levels close to normal values. These results imply that there is a significant association between improved glycemic control and Tocomin or Lovastatin. Although a detailed investigation is needed to elucidate the possible mechanism(s) involved, it is intriguing to postulate that both Tocomin and Lovastatin being potent antioxidants may have effectively protected the β-cells from total damage by STZ and/or glucotoxicity.