Protocatechualdehyde restores endothelial dysfunction in streptozotocin-induced diabetic rats.

Background: The present study was conducted with the aim of clarifying the effects of protocatechualdehyde (PCA) on the endothelial function in streptozotocin (STZ)-induced diabetic rats.

Methods: Sprague 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), p22, p47 and Cu/Zn-SOD were measured by Western blot analysis.

Results: PCA 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 p47 and p22 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.

Conclusions: Our 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.