Thymoquinone attenuates monocrotaline-induced pulmonary artery hypertension via inhibiting pulmonary arterial remodeling in rats

Background: Pulmonary artery remodeling induced by excess proliferation, migration and apoptosis resistance of pulmonary arterial smoothmuscle cells (PASMCs) is a key component in pulmonary artery hypertension (PAH). Thymoquinone (TQ) triggers cancer cells apoptosis through multiple mechanisms. In addition, TQ inhibits migration of human nonsmall-cell lung cancer cells and human glioblastoma cells. Objectives: In the current study, we investigated effects of TQ on MCT-induced PAH in rats and its underlying mechanisms. Methods: After 2 weeks of monocrotaline injection (MCT, 60 mg/kg), Male Sprague-Dawley rats received TQ (8 mg/kg, 12 mg/kg, 16 mg/kg) or olive oil per day for 2 weeks. Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were examined 4 weeks later. In addition, TUNEL, PCNA, alpha-SMA, Bax and Bcl-2 were detected by immunohistochemistry staining. Bax, Bcl-2, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) MMP2, MMP9 and activation of p38MAPK and NF-kappa B were assessed by Western blot. Results: MCT-induced an increase in pulmonary blood pressure and right ventricular hypertrophy, which were attenuated by TQ treatment. TQ also blocked MCT-induced pulmonary arterial remodeling, proliferation of PASMCs, elevation of MMP2 and downregulation of ratio of Bax/Bcl-2, cleaved caspase-3 and cleaved PARP. Furthermore, TQ inhibited MCT-induced activation of p38MAPK and NF-kappa B. Conclusions: TQ ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via p38MAPK/NF-kappa B signaling pathway in rats. (C) 2016 Elsevier Ireland Ltd. All rights reserved.