Protective Potential of Morin in Ifosfamide-Induced Lung Toxicity: Modulation of Oxidative Stress, Inflammation and Apoptosis Parameters

In this study, the protective effect of morin against lung toxicity induced by ifosfamide (IFO), a widely used drug in cancer treatment, was investigated. Thirty-five male Sprague Dawley rats were divided into five groups: Control, Morin (200 mg/kg), IFO and two different Morin doses (IFO + Morin 100 mg/kg and IFO + Morin 200 mg/kg). Rats were given morin 100 mg/kg or 200 mg/kg for 2 days and on the second day, IFO 500 mg/kg was administered as a single dose. Biochemical and molecular methods analyzed oxidative stress, inflammation, autophagy and apoptosis markers. According to the data obtained, IFO increased malondialdehyde (MDA) levels in lung tissue, while decreasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) activities and glutathione (GSH) levels. However, it was observed that morin administration decreased MDA levels and increased GSH levels and GPx, SOD, CAT activities. IFO administration inhibited the expression of B-cell lymphoma-2 (Bcl-2) and the nuclear factor erythroid 2-related factor 2 (Nrf-2) /heme oxygenase-1 (HO-1) pathway, while increasing levels of nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), Bcl-2-associated x protein (Bax), and cysteine aspartate specific protease-3 (Caspase-3). However, Morin decreased NF-κB and iNOS levels and inhibited inflammation by activating the Nrf-2/HO-1 pathway and prevented apoptosis by decreasing Bax and Caspase-3 and increasing Bcl-2. It also caused a decrease in Beclin-1 levels. According to the findings, IFO by affecting various signaling pathways in lung tissue, causing cellular damage, while morin demonstrated protective qualities against this damage.