Attenuation of oxidative stress-induced vascular endothelial dysfunction by thymoquinone

This study aimed to assess the effects of thymoquinone (TQ) on pyrogallol-induced endothelial dysfunction in isolated rabbit aorta. The protective effects of TQ were examined by incubating aortic rings in TQ concomitant with pyrogallol. The results revealed that pyrogallol produced significant enhancement of phenylephrine-induced contraction and impairment of acetylcholine-induced relaxation. Pyrogallol caused a significant increase in lipid peroxidation and reduction in the level of superoxide dismutase and reduced glutathione in the aortic homogenates. In addition, pyrogallol produced a significant decrease in nitrite/nitrate concentrations (NOx), constitutive nitric oxide synthase (cNOS) activity and an increase in inducible nitric oxide synthase (iNOS) activity in the aortic homogenates. These changes were counteracted by TQ co-incubation as TQ attenuated pyrogallol-induced impairment in vascular reactivity in a dose-dependent manner. Furthermore, TQ showed potent antioxidant activity as well as causing a significant increase in NOx and cNOS activity, and depression in iNOS activity. These results suggest that TQ can protect against pyrogallol-induced endothelial dysfunction which probably results from its potent antioxidant capacity that leads to an increase in NO production as well as its ability to enhance the generation and bioavailability of NO.