Oxidative stress and gene expression of antioxidants enzymes in monocrotaline-induced pulmonary hypertension following the administration of antiretroviral medications in rats

Abstract

Objectives: Pulmonary hypertension (PH) is a severe life-threatening pulmonary vasculopathy. This study investigated the effects of zidovudine (AZT) and/or ritonavir (RTV) in the oxidative process of monocrotaline (MCT)-induced PH in rats. Materials and Methods: Forty male Sprague-Dawley rats weighing between 200 and 250 g were randomized into five different groups (n = 8 per group). A single dose intraperitoneal injection of MCT (60 mg/kg) was administered to all the rats in four of the groups. Daily oral administration of the antiretroviral (ARV) medications – (1) AZT-only (100 mg/kg); (2) RTV only (30 mg/kg); (3) AZT+ RTV (100+30 mg/kg); and (4) the untreated group had equivalent volume of saline for 28 days, respectively, while the (5) control group had neither MCT nor ARV. Gene expression using RT-PCR for the antioxidants and laboratory assay for lipid peroxidation was analyzed. Results: A significantly higher mRNA gene expression of catalase, superoxide dismutase and glutathione peroxidase in the treated rats was observed compared to the untreated. There was an increase in malondialdehyde (MDA) in the heart tissues of untreated rats (37.01 ± 1.16 nmol/g, P < 0.0001) compared to the control group (3.46 ± 0.97 nmol/g) with an associated reduction in MDA by the ARVs. Furthermore, an increase in the total antioxidant capacity in AZT (0.85 ± 0.02 nmol/g, P < 0.0001), RTV (0.63 ± 0.03 nmol/g, P < 0.0001), and combination of AZT/RTV (0.77 ± 0.06 nmol/g, P < 0.0001) compared to untreated (0.28 ± 0.03) rats. Conclusion: AZT and RTV ameliorate PH in experimental rats. This study demonstrated that MCT-induced PH generates ROS in rats and the protective role of ARV drugs in the treatment of PH.