22 August 2011
Natural antioxidant dihydroxybenzyl alcohol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human endothelial cells
Sarah M. WeakleyABCDEF, Jun JiangABCD, Jianming LuABCD, Xinwen WangABCD, Peter H. LinAD, Qizhi YaoAD, Changyi ChenABCDEFGDOI: 10.12659/MSM.881926
Med Sci Monit 2011; 17(9): BR235-241
Abstract
Background: 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.
Results: 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.
Conclusions: 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.
Keywords: Oxidative Stress - drug effects, Pulmonary Artery - physiopathology, Nitric Oxide Synthase Type III - metabolism, Glutathione - metabolism, Free Radical Scavengers - pharmacology, Endothelium, Vascular - physiopathology, Endothelial Cells - metabolism, Down-Regulation - drug effects, Cell-Free System, Benzyl Alcohols - pharmacology, Antioxidants - pharmacology, Ritonavir - adverse effects, Superoxides - metabolism, Sus scrofa
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
15 Apr 2024 : Laboratory Research
The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in OsteoarthritisMed Sci Monit In Press; DOI: 10.12659/MSM.943738
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952