Abstract
Cyclophosphamide (CP)-induced lung toxicity is a remaining obstacle against the beneficial use of this chemotherapeutic agent. More considerations were given to the role of Alogliptin (ALO) in ameliorating CP-induced toxicities in many tissues. We designed this study to clarify the protective potential of ALO against CP-induced lung toxicity in rats. ALO was administered for 7 days. Single-dose CP was injected on the 2nd day (200 mg/kg: i.p.) to induce lung toxicity. Rats were divided into four groups: control, ALO-treated, CP-treated and ALO + CP-treated group. Leucocytic count, total proteins, LDH activity, TNF-α, and IL-6 were estimated in the bronchoalveolar lavage fluid (BALF). The oxidative/antioxidants (MDA, Nrf2, TAO and GSH), inflammatory (NFκB), fibrotic (TGF-β1) and apoptotic (PI3K/Akt/FoxO1) markers in pulmonary homogenates were biochemically evaluated. Rat lung sections were examined histologically (light and electron microscopic examination) and immunohistochemically (for iNOS and CD68 positive alveolar macrophages). CP significantly increased oxidative stress, inflammation, fibrosis, and apoptosis markers as well as deteriorated the histopathological pulmonary architecture. These hazardous effects were significantly ameliorated by ALO treatment. ALO protected against CP-induced lung toxicity by mitigating the oxidative, inflammatory and fibrotic impacts making it a promising pharmacological therapy for mitigating CP-induced lung toxicity.Graphical abstract
Highlights
Cyclophosphamide (CP) is a very potent widely used alkylating agent
Its limited use is due to its numerous organ damage and toxicity (Suddek et al 2012; Ahlmann and Hempel 2016)
The toxicity of CP is produced mainly by its toxic metabolite acrolein that causes cellular apoptosis, encourage oxidative stress in addition to inflammation leading to lethal numerous organs injury (El-Kashef 2018)
Summary
Cyclophosphamide (CP) is a very potent widely used alkylating agent. It is used as antineoplastic and immunosuppressive drug (Moignet et al 2013). CP is associated with genotoxicity and numerous hazardous impacts on numerous organs due to its capability to stimulate oxidative burden with consequent cell death (ElEmam 2020). Among these toxicities are cardiotoxicity (Iqubal et al 2019), hepatotoxicity (Abdelfattah-Hassan et al 2019), nephrotoxicity (Sharma et al 2017), in addition to lung toxicity (El-kashef 2018; Abdel-Latif et al 2020)
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