Protective use of alpha pinene in methotrexate-induced oxidative lung damage in rats

Methotrexate, used in the treatment of various cancers, induce oxidative stress, inflammatory response, apoptotic cell death and ultimately toxic lung damage when used for a long time or in excessive doses. Prevention of overproduction of reactive oxygen species and maintenance of cellular redox balance can be facilitated by the use of various natural antioxidants and essential oils. The aim of this study was to investigate the protective role of Alpha Pinene, a plant component known to have antioxidant, anti-inflammatory and cytoprotective properties, against Methotrexate-induced lung damage in rats. For this purpose, 35 adult male rats were randomly divided into 5 groups as Control, Vehicle, Methotrexate (20 mg/kg, single dose), Alpha Pinene (50 mg/kg/day) and Methotrexate+Alpha Pinene. At the end of the 14-day experimental period, the removed lungs were first weighed, then oxidative stress (superoxide dismutase, catalase and malondialdehyde) and apoptosis (APAF-1 and Caspase-3) parameters were measured, then the Heat Shock Protein 70 levels were determined, and finally Haematoxylin-Eosin and Masson's Trichrome stains were performed to evaluate histologic tissue damage. The data obtained revealed that Alpha Pinene significantly reduced Methotrexate induced changes in the oxidative stress and apoptosis parameters and Heat Shock Protein 70 levels. It was also shown to have a protective effect on the lungs against acute Methotrexate toxicity, preventing alveolar epithelial damage, congestion, inflammatory cell infiltration and alveolar degeneration despite the presence of mild fibrosis and interstitial edema. Alpha Pinene can be considered to be a highly valuable protective agent against Methotrexate-induced lung injury.