The present study aimed to investigate the possible ototoxic interaction between digoxin (DX) and each of sodium salicylate (SS) and furosemide (FS). Preyer's reflex (hearing test) was performed in rats and guinea pigs. Each of Na+/k+/atpase activity, outer hair cells (OHCs) count, inner hair cells (IHCs) count and histopathological examination of cochlea were evaluated in guinea pigs. The utilized animals included 230 Sprague-Dawely rats and 75 guinea pigs. Experiments were done on two phases. In phase I, single treatment of different dose levels of each SS, FS and DX were tested. In phase II, combined treatments were applied where one dose of SS or FS was administered in combination with two dose levels of DX. In rats, combined treatment of SS and DX didn't significantly affect Preyer's reflex score. On the other hand, combined treatment of FS (100 mg/kg) and DX (30 mg/kg) significantly increased Preyer's reflex score. In guinea pigs, combined treatment of DX with each of SS or FS didn't significantly affect Na+/k+/atpase activity. Combined treatment of DX (0.2 mg/kg or 0.3 mg/kg) with SS (200 mg/kg) decreased OHCs count. However, the combined treatment with 0.3 mg/kg of DX significantly increased IHCs. On the other side, combined treatment of FS and DX didn't significantly affect OHCs or IHCs count. In parallel, histopathological examination of cochlea indicated similar finding.
The obtained results may indicate that co-administration of DX with SS or FS possesses ototoxic potential.