Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
Med Sci Monit. 2011 Sep;17(9):BR235-41. doi: 10.12659/msm.881926.
Patients with HIV have an increased incidence of pulmonary artery hypertension. This study was designed to determine if the naturally occurring antioxidant dihydroxybenzyl alcohol (DHBA) could counteract the deleterious effects of ritonavir (RTV), an HIV-protease inhibitor known to impair endothelial function and increase oxidative stress.
MATERIAL/METHODS: Antioxidant assays were performed on DHBA in a cell free system. Glutathione (GSH) levels were measured in human pulmonary artery endothelial cells (HPAEC) to determine the effect of DHBA on the level of oxidative stress in cells treated with RTV. Myograph analysis was performed on porcine pulmonary artery (PA) rings after treatment with RTV and/or DHBA. Likewise, reactive oxygen species (ROS) production was assessed in porcine PA rings after RTV +/- DHBA using a lucigenin reaction. Immunohistochemical staining for endothelial nitric oxide synthase (eNOS) was also performed in porcine PAs treated as above.
DHBA demonstrated significant antioxidant activity in a cell free system that surpassed that of vitamin C. Also, treatment with DHBA reduced RTV-induced reduction in endothelium-dependent vasorelaxation and eNOS staining and increased superoxide anion levels. Meanwhile, there was a reversal in RTV-induced oxidative stress leading to reduced GSH levels in HPAECs after treatment with DHBA.
These findings suggest that the naturally occurring antioxidant DHBA reduces the impairment of vasomotor functions caused by RTV in porcine PAs and reduces oxidative stress caused by RTV in HPAEC and porcine PA rings. This study indicates that DHBA may have clinical applications in the prevention or treatment of antiretroviral drugs-associated vascular complications in patients with HIV.
HIV 患者肺动脉高压的发病率增加。本研究旨在确定天然抗氧化剂二羟苯甲醇（DHBA）是否可以抵消ritonavir（RTV）的有害影响，ritonavir 是一种已知会损害内皮功能并增加氧化应激的 HIV 蛋白酶抑制剂。
材料/方法：在无细胞体系中对 DHBA 进行抗氧化测定。测量人肺动脉内皮细胞（HPAEC）中的谷胱甘肽（GSH）水平，以确定 DHBA 对用 RTV 处理的细胞中氧化应激水平的影响。用 RTV 和/或 DHBA 处理后，对猪肺动脉（PA）环进行肌描分析。同样，使用鲁米诺反应评估 RTV +/- DHBA 处理后猪 PA 环中活性氧（ROS）的产生。还对用上述方法处理的猪 PA 进行内皮型一氧化氮合酶（eNOS）的免疫组织化学染色。
DHBA 在无细胞体系中表现出显著的抗氧化活性，超过了维生素 C。此外，DHBA 处理可减少 RTV 诱导的内皮依赖性血管舒张和 eNOS 染色减少，并增加超氧阴离子水平。同时，DHBA 处理可逆转 RTV 诱导的氧化应激，导致 HPAEC 中 GSH 水平降低。
这些发现表明，天然抗氧化剂 DHBA 可减少 RTV 引起的猪 PA 血管运动功能障碍，并减少 RTV 引起的 HPAEC 和猪 PA 环中的氧化应激。这项研究表明，DHBA 可能在预防或治疗 HIV 患者抗逆转录病毒药物相关血管并发症方面具有临床应用前景。
