TY - JOUR T1 - Protection from Gentamicin Ototoxicity by Iron Chelators in Guinea Pig <em>In Vivo <sup>,</sup> </em> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 369 LP - 377 VL - 282 IS - 1 AU - Ben-Bo Song AU - David J. Anderson AU - Jochen Schacht Y1 - 1997/07/01 UR - http://jpet.aspetjournals.org/content/282/1/369.abstract N2 - This study details the prevention of gentamicin-induced hearing loss in guinea pig in vivo. The approach is based on our recent demonstrations of a redox-active gentamicin-iron complex in vitro and partial attenuation of gentamicin-induced hearing loss by the iron chelators deferoxamine and 2,3-dihydroxybenzoate. In our study, guinea pigs receiving injections of gentamicin (120 mg/kg body weight daily × 19 days) developed a progressive threshold shift reaching 50 to 70 dB at 18 kHz. Concurrent treatment with different doses of 2,3-dihydroxybenzoate (30–300 mg/kg/day) reduced the threshold shift to 25 to 15 dB. Coinjection of gentamicin with dihydroxybenzoate (100 mg/kg/day) plus mannitol (15 mg/kg/day) yielded complete functional and morphological protection from gentamicin ototoxicity although partial protection was observed with combinations of dihydroxybenzoate and deferoxamine. Dihydroxybenzoate also attenuated gentamicin-induced vestibular toxicity. The iron chelators and radical scavengers affected neither serum levels nor the antimicrobial efficacy of gentamicin against Escherichia coli. These results confirm that iron and free radicals play a crucial role in the toxic side effects of gentamicin. Furthermore, they suggest that iron chelators, which are well-established drugs in clinical therapy, may be promising therapeutic agents to reduce aminoglycoside ototoxicity. The American Society for Pharmacology and Experimental Therapeutics ER -