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The effects of chronic lead acetate treatment on alterations of Auditory Brainstem Response (ABR) induced by gentamicin and amikacin were tested in guinea pigs. This study was designed to investigate the hypothesis that aminoglycoside antibiotics and lead via their effects on phosphoinositide pathway and calcium channels may influence ototoxicity mechanisms as tested on the auditory brainstem response. Intramuscular injection of different doses of gentamicin (5, 10 mg/kg/day) and amikacin (150, 300 mg/kg/day) for three weeks induced hearing loss. Administration of lead acetate (0.05%, 35 days) in drinking water changed ABR (absolute wave latency). The gentamicin-induced alteration of ABR were attenuated by chronic lead acetate pretreatment in guinea pig. Obtained data suggest the interactions between chronic lead acetate and aminoglycoside antibiotics in alterations of auditory functions which could be accounted for, at least partially, by perturbations of the phosphoinositide and calcium cascades within the inner ear.