Anti-Oxidative Effect of Vitamin D Analog on Incipient Vascular Lesion in Non-Obese Type 2 Diabetic Rats

Abstract

Background/Aims: Vascular disease is one of the critical complications of diabetes. A growing body of evidence suggests that oxidative stress plays a key role for vascular disease progression. Recent studies have demonstrated a strong link between vitamin D and cardiovascular disease. Methods: We investigated the anti-oxidative effects of a vitamin D analog, 22-oxacalcitriol (maxacalcitol), on vascular lesions in type 2 diabetic rats. We used Spontaneously Diabetic Torii (SDT) rats, a model of non-obese type 2 diabetes. At 20 weeks of age, SDT rats were randomly divided into three groups: diabetes mellitus (DM, n = 10), DM + maxacalcitol (DM + D, n = 10), and DM + insulin (DM + I, n = 10). The rats were sacrificed at 30 weeks for the evaluation of blood and urine samples as well as histopathology and mRNA expression in the aorta. Results: Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion and the number of 8-OHdG-positive cells were significantly lower in the DM + I and DM + D groups than in the DM group. Real-time polymerase chain reaction analysis demonstrated that NADPH p22 phox and NADPH p47 phox mRNA levels were markedly decreased in the DM + I and DM + D groups compared with the DM group. Furthermore, the mRNA expression of MCP-1, ICAM-1 and VCAM-1 was significantly reduced in the DM + I and DM + D groups compared with the DM group. Conclusion: Our results suggest that the vasoprotective effects of vitamin D are mediated by reducing oxidative stress.