Sitagliptin ameliorates busulfan-induced pulmonary and testicular injury in rats through antioxidant, anti-inflammatory, antifibrotic, and antiapoptotic effects

Abstract

Abstract Busulfan (BUS) is an anticancer agent with serious adverse effects on various body organs, including the lung and testis. Sitagliptin was proven to have antioxidant, anti-inflammatory, antifibrotic, and antiapoptotic effects. This study aims to evaluate whether sitagliptin, a DPP4I, ameliorates BUS-induced pulmonary and testicular injury in rats. Male Wistar rats were split into control, sitagliptin (10 mg/kg), BUS (30 mg/kg), and sitagliptin + BUS groups. Weight change, lung and testis indices, serum testosterone, sperm parameters, markers of oxidative stress [malondialdehyde (MDA) and reduced glutathione (GSH)], inflammation [tumor necrosis factor-alpha (TNF-α)], and relative expression of sirtuin1 (SIRT1) and forkhead box protein type O1 (FOXO1) genes were estimated. Histopathological examination of lung and testicular tissues was done to detect architectural changes [Hematoxylin & Eosin (H&E)], fibrosis (Masson’s trichrome), and apoptosis (caspase-3). Sitagliptin treatment reduced body weight loss, lung index, lung and testis MDA, serum TNF-α and sperm abnormal morphology, and increased testis index, lung and testis GSH, serum testosterone, sperm count, viability and motility. SIRT1/FOXO1 balance was restored. Also, sitagliptin attenuated fibrosis and apoptosis in lung and testicular tissues via reducing collagen deposition and caspase-3 expression. Accordingly, sitagliptin ameliorated BUS-induced pulmonary and testicular damage in rats via attenuating oxidative stress, inflammation, fibrosis, and apoptosis.