Ivermectin modulates lung toxicity induced by γ-radiation viaTLR4/ NF-κβ /MAPK pathways

Abstract

Abstract Background Radiation is pro-inflammatory in nature because of its ability to generate reactive oxygen species (ROS), cytokines, chemokines, and growth factors with associated inflammatory cells. The current study aims to evaluate the pulmonary protective effects of ivermectin against the high dose of γ- irradiation in adult male albino rats by illuminating the effect of lung receptors toll-like receptors (TLR4), transforming growth factor beta (TGF-β), fibroblast growth factor (FGF), and Nuclear factor-kappa B (NF-κβ), as inflammatory mediators.Methods Male albino rats were given ivermectin orally (3.7mg/kg/day for 14 days), then exposed to a high dose of γ-radiation (30 Gy) in 10 fractions, 5 fractions per week.Results Gamma-radiation not only boosted the activity of lactate dehydrogenase A (LDHA) in lung tissue but also induced a significant disruption in the antioxidants that led to lung damage via a significant elevation of activities of mitogen-activated protein kinase (MAPK), prostaglandin 2 (PG2), TLR4, TGF-β, NF-κβ, and FGF levels. In the present study, ivermectin reduced pulmonary damage by suppressing ROS generation and reestablishing the activities of MAPK, LDHA, and levels of FGF, PG2, TGF-β, NF-κβ, and TLR4 to nearly normal in the lungs. The histopathological study confirmed the biochemical studies.Conclusion Ivermectin modulates lung toxicity induced by γ-radiation via TLR4/NF-κβ /MAPK pathways.