PDF(Pubmed)
Abstract：
The toxicity of inhaled particulate air pollution perseveres even at lower concentrations than those of the existing air quality limit. Therefore, the identification of safe and effective measures against pollutant particles-induced vascular toxicity is warranted. Carnosol is a bioactive phenolic diterpene found in rosemary herb, with anti-inflammatory and antioxidant actions. However, its possible protective effect on the thrombotic and vascular injury induced by diesel exhaust particles (DEP) has not been studied before. We assessed here the potential alleviating effect of carnosol (20 mg/kg) administered intraperitoneally 1 h before intratracheal (i.t.) instillation of DEP (20 μg/mouse). Twenty-four hours after the administration of DEP, various parameters were assessed. Carnosol administration prevented the increase in the plasma concentrations of C-reactive protein, fibrinogen, and tissue factor induced by DEP exposure. Carnosol inhibited DEP-induced prothrombotic effects in pial microvessels in vivo and platelet aggregation in vitro. The shortening of activated partial thromboplastin time and prothrombin time induced by DEP was abated by carnosol administration. Carnosol inhibited the increase in pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor α) and adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin) in aortic tissue. Moreover, it averted the effects of DEP-induced increase of thiobarbituric acid reactive substances, depletion of antioxidants and DNA damage in the aortic tissue. Likewise, carnosol prevented the decrease in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) caused by DEP. We conclude that carnosol alleviates DEP-induced thrombogenicity and vascular inflammation, oxidative damage, and DNA injury through Nrf2 and HO-1 activation.
摘要：
即使在低于现有空气质量限值的浓度下，吸入颗粒空气污染的毒性也会持续存在。因此,有必要确定针对污染物颗粒引起的血管毒性的安全有效措施。鼠尾草是迷迭香草本植物中发现的生物活性酚类二萜，具有抗炎和抗氧化作用。然而,其对柴油机废气颗粒（DEP）引起的血栓和血管损伤的可能保护作用尚未研究。我们在此评估了在气管内（i.t.）滴注DEP（20μg/小鼠）前1小时腹膜内施用鼠尾草酚（20mg/kg）的潜在缓解作用。服用DEP后24小时，评估了各种参数。Carnosol给药阻止了C反应蛋白血浆浓度的增加，纤维蛋白原，DEP暴露诱导的组织因子。鼠尾草酚在体内抑制DEP诱导的绒毛膜微血管血栓形成作用，在体外抑制血小板聚集。肌醇减轻了DEP诱导的活化部分凝血活酶时间和凝血酶原时间的缩短。Carnosol抑制促炎细胞因子（白细胞介素-6和肿瘤坏死因子α）和粘附分子（细胞间粘附分子-1，血管细胞粘附分子-1，E-选择素，和P-选择素）在主动脉组织中。此外，它避免了DEP诱导的硫代巴比妥酸反应性物质增加的影响，主动脉组织中抗氧化剂的消耗和DNA损伤。同样，鼠尾草酚可防止DEP引起的核因子红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）表达的降低。我们得出的结论是，鼠尾草酚可以缓解DEP诱导的血栓形成和血管炎症，氧化损伤，和DNA损伤通过Nrf2和HO-1激活。
