Perillyl Alcohol Suppresses Monocrotaline-Induced Pulmonary Arterial Hypertension In Rats Via Anti-Remodeling, Anti-Oxidant, And Anti-Inflammatory Effects

Background: Pulmonary arterial hypertension (PAH) is a disastrous disease that current treatments cannot prevent its progression. The present study investigated the effects of perillyl alcohol (PA), a natural monoterpene, on the experimental PAH in male Wistar rats.Methods: Rats divided into eight groups of control, Monocrotaline (MCT), MCT+vehicle, and MCT+PA with doses of 20, 30, 40, 50, and 60 mg/kg. PAH was induced by a single injection of monocrotaline (60 mg/kg) on day 0. The animals in the groups of MCT+vehicle and MCT+PA received the vehicle or PA from day 22 to 42 once a day. On day 43, under general anesthesia, right ventricular systolic pressure (RVSP), as an index of pulmonary artery systolic pressure, and the ratio of the right ventricle to the left ventricle plus septum weight, as the right ventricular hypertrophy index (RVHI), were measured. Also, some histological and biochemical indices were assessed in the lung tissue.Results: MCT significantly (p < .001) enhanced the RVSP and RVHI compared to the control group (89.4 +/- 8.2 vs 23 +/- 3.3 mmHg & 0.63 +/- 0.08 vs 0.26 +/- 0.04 respectively). It also increased oxidative stress and inflammatory cytokines and reduced Bax/Bcl2 ratio. Treatment with PA significantly recovered RVSP and hypertrophy index and suppressed vascular cell proliferation, oxidant production, and inflammatory processes.Conclusion: PA exerted noticeable protective and curative effects against MCT-induced PAH and pulmonary vascular remodeling through inhibiting cellular proliferation, oxidative stress, and inflammation. Therefore, PA can be considered as a new therapeutic goal for the treatment of PAH.