Myrtenol ameliorates inflammatory, oxidative, apoptotic, and hyperplasic effects of urethane-induced atypical adenomatous hyperplasia in the rat lung.

Lung atypical adenomatous hyperplasia (AAH) is a forerunner of pulmonary adenocarcinoma. The drugs being utilized in the remediation of this type of hyperplasia have some adverse impacts. The present research focused on the potential anti-hyperplasia effect of myrtenol, an herbal terpenoid, on urethane-induced lung AAH in rats. Rats were injected with urethane (1.5 g/kg) thrice at 48 h intervals, and 20 weeks later, the animals were treated with 50 mg/kg myrtenol intraperitoneally once a day for 1 week. The ELISA method was used to measure inflammatory cytokines and oxidative parameters in the lung tissue and bronchoalveolar lavage fluid (BALF). The expression of NFκB and apoptotic/antiapoptotic factors (P53/Bcl-2) was evaluated by western blot and immunohistochemistry, respectively. H&E staining was performed for histopathological investigation. Histopathology confirmed the anti-hyperplasia effect of myrtenol, which was evidenced by the reduction of bronchoalveolar wall thickness and inflammation score. It also decreased hyperplasia progression by reducing Bcl-2, IL-10, p53, and Ki67. Compared with the urethane group, myrtenol normalized the activity of the oxidative stress markers malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Moreover, it showed an anti-inflammatory effect by decreasing lung and BALF IL-1β levels and NFκB expression. Myrtenol may have a promising effect on lung cancer treatment by counteracting lung hyperplasia via modulation of inflammation, oxidative stress, and apoptosis.