Possible ameliorative effects of pentoxifylline on cisplatin-induced ototoxicity in rats: a study with hearing test, light, and scanning electron microscopy

Abstract

Cisplatin is an antineoplastic drug widely used to treat various types of cancer. Ototoxicity is still cisplatin’s most critical side-effect. Some patients may experience dose limitations due to hearing loss. Pentoxifylline (PX) exhibits powerful antioxidant, anti-inflammatory, and immune-regulatory effects. Our study was designed to investigate the protective effects of pentoxifylline on cisplatin-induced ototoxicity. Forty adult male healthy Sprague-Dawley rats were used through the entire experiment. Four groups of animals were categorized: Group I (control group); Group II (PX group) received 25 mg/kg/day of oral PX by gavage for 8 consecutive days; Group III (Cisplatin group) received cisplatin single intraperitoneal dose of 10 mg/kg; Group IV (PX + Cisplatin group) received 25 mg/kg/day of oral PX by gavage for 8 successive days and a single intraperitoneal dose of 10 mg/kg cisplatin at the 4th day. First and 9th-day Distortiondistortion-product otoacoustic emissions (DPOAE) tests were conducted. An intracardiac blood sample was collected for total antioxidant capacity (TAC) measurement, and the cochleae of rats were examined histopathologically. A significant reduction in serum TAC value was detected in the cisplatin group, while PX treatment significantly reduced TAC. Cisplatin decreased the DPOAE amplitudes in rats; conversely, the PX+cisplatin group showed a significant increase at all frequencies. Upon histopathological examination, the Ciplastin group revealed perturbation of the normal architecture of the organ of Corti, increased collagen deposition and marked expression of caspase-3, while the PX+cisplatin group revealed preserved architecture of the organ of Corti, minimal collagen deposition and downregulation of Caspase-3 expression. As evidenced by our findings and results from DPOAE results, biochemical findings, histological and ultrastructural analyses, PX significantly protects rats against ototoxicity caused by cisplatin.