Histological and immunohistochemical study on the effect of bosutinib on the lung of adult male albino rats and the possible ameliorating effect of N-acetyl cysteine

Abstract

AbstractBackground: bosutinib is in a group of medications named tyrosine kinase inhibitors and is utilized to treat definite type of chronic myeloid leukemia. It might inhibit an abnormal protein that stimulates cancer cells to proliferate. bosutinib administration have some respiratory complications. N- acetylcysteine (NAC) is drug that could be utilized to treat conditions as cystic fibrosis and asthma. NAC is a byproduct of glutathione.Objective: the target of this work is to estimate the impact of bosutinib, on the rat's lung and the potential protective effect of NAC.Materials and Methods: this study was carried on forty eight adults male rats. They were divided into control group, NAC treated group, bosutinib treated group and finally, bosutinib and NAC treated group. At the end of experiment, the lung tissues were processed for biochemical, histological and immunohistochemical studies.Results: bosutinib treated group revealed variable degree of histological alterations. Some alveoli appeared collapsed with presence of hyaline material deposition in others, they were mainly lined by type II pneumocytes. The inter-alveolar septa were thick. Cellular infiltration and congested blood vessels with perivascular fibrosis were noticed. Ultrastructurally, type I and type II pneumocytes exhibited degenerative changes. Biochemical results revealed marked increase in the malondialdehyde (MDA) and a marked decrease in the superoxide dismutase (SOD) and glutathione (GSH) levels. These changes were less evident by co-administration of NAC.Conclusion: bosutinib has a toxic effect on the lung tissue which could be ameliorated by coadministration of NAC.Key words: bosutinib, lung, NAC, caspase-3, iNOS, α-SMA.