Protocatechualdehyde restores endothelial dysfunction in streptozotocin-induced diabetic rats.

Abstract

BackgroundThe present study was conducted with the aim of clarifying the effects of protocatechualdehyde (PCA) on the endothelial function in streptozotocin (STZ)-induced diabetic rats.MethodsSprague Dawley (SD) rats were intraperitoneally injected with STZ (single dose of 60 mg/kg). Diabetic model rats were given PCA (25 mg/kg/day) via gavage feeding for 6 weeks. Vascular function was studied; superoxide anion and nitrotyrosine levels were assessed; and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase as well as total superoxide dismutase (SOD) activity were detected. Protein expression of phosphorylated endothelial nitric oxide synthase (P-eNOS), total endothelial nitric oxide synthase (T-eNOS), p22phox, p47phox and Cu/Zn-SOD were measured by Western blot analysis.ResultsPCA treatment significantly ameliorated the impairment of acetylcholine- evoked endothelium-dependent relaxation, with no obvious effects observed on the blood glucose or body weight in the STZ-induced diabetic rats. Expression levels of aortic P-eNOS/T-eNOS and endothelial nitric oxide synthase (eNOS) activity were decreased in STZ-induced diabetic rats while they remained unchanged in PCA-treated rats. However, PCA treatment improved oxidative inactivation of nitric oxide (NO) and decreased the levels of superoxide anion and nitrotyrosine in the aorta of STZ-induced diabetic rats; these were achieved by reducing the level of nitrotyrosine and down-regulating p47phox and p22phox expression, as well as up-regulating Cu/Zn-SOD protein expression. Consistently, the effects observed were associated with a decrease in NADPH oxidase activity and an increase in total SOD activity.ConclusionsOur results indicate that the administration of PCA may be protective against oxidative stress and may restore endothelial function by improving vascular NO oxidative inactivation in diabetic condition.