Berberine alleviated methotrexate-induced oxidative and inflammatory lung injury by modulating Nrf2 signaling in rats

Abstract

Methotrexate (MTX), a medication commonly utilised in the management of autoimmune disorders and cancer, has been observed to precipitate pulmonary tissue injury when administered over an extended period. This may result in a range of adverse effects, including psychological and physiological distress, in patients. Berberine (BER), a molecule that has been employed in traditional therapeutic practices for centuries, is an alkaloid derivative with a multitude of pharmacological activities. The objective of the present study was to examine the therapeutic potential of BER in counteracting pulmonotoxicity induced by systemic MTX administration for the first time. In this experimental model, rats were subjected to a single intraperitoneal injection of 20 mg/kg of MTX on the first day in order to induce lung injury. Following this, the rats were then administered BER treatments at doses of 1 mg/kg or 2 mg/kg for a period of three consecutive days. Administration of MTX resulted in a significant suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) levels in the lung tissue of rats when compared to the control group (∼7.0 fold; p < 0.01). Furthermore, MTX administration significantly induced lipid peroxidation, inflammation, and endoplasmic reticulum stress levels in comparison with the control group, leading to severe pulmonary histopathological symptoms (p < 0.001). Conversely, the administration of BER treatments led to a significant alleviation of degenerative biochemical and histopathological findings, achieved by modulating Nrf2 signalling (p < 0.05). Consequently, the present findings imply that BER may exert a positive effect on MTX-induced oxidative pulmonary damage, at least in part, by modulating the Nrf2 pathway.