Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Exp Biol Med (Maywood). 2012 Sep;237(9):1032-8. doi: 10.1258/ebm.2012.012107. Epub 2012 Aug 28.
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.
本研究旨在评估百里醌(TQ)对离体兔主动脉焦儿茶酚诱导的内皮功能障碍的影响。通过在 TQ 与焦儿茶酚同时孵育主动脉环来检查 TQ 的保护作用。结果表明,焦儿茶酚可显著增强苯肾上腺素诱导的收缩作用,并损害乙酰胆碱诱导的舒张作用。焦儿茶酚引起主动脉匀浆中脂质过氧化增加,超氧化物歧化酶和还原型谷胱甘肽水平降低。此外,焦儿茶酚还导致主动脉匀浆中硝酸盐/亚硝酸盐浓度(NOx)、组成型一氧化氮合酶(cNOS)活性降低,诱导型一氧化氮合酶(iNOS)活性升高。TQ 共孵育可逆转这些变化,因为 TQ 以剂量依赖的方式减轻了焦儿茶酚诱导的血管反应性损伤。此外,TQ 表现出很强的抗氧化活性,同时显著增加了 NOx 和 cNOS 活性,降低了 iNOS 活性。这些结果表明,TQ 可以预防焦儿茶酚诱导的内皮功能障碍,这可能是由于其强大的抗氧化能力导致 NO 生成增加,以及增强 NO 的产生和生物利用度的能力。