ATTENUATION OF GENTAMICIN OTOTOXICITY BY GLUTATHIONE IN THE GUINEA-PIG IN-VIVO

The effect of glutathione co-therapy on the expression of gentamicin o totoxicity was tested in pigmented guinea pigs. The first group of ani mals was injected with gentamicin (100 mg/kg body weight/day) for two weeks followed by 10 weeks of rest. A second group received glutathion e by gastric gavage immediately prior to each gentamicin injection. Tw o groups of controls were treated either with saline injections or glu tathione gavage alone. Auditory brainstem responses, taken at 2-week i ntervals, revealed a progressive gentamicin-induced hearing loss reach ing a 30 to 40 dB threshold shift at 2 kHz, approximately 60 dB at 8 k Hz and 80 dB at 18 kHz. Glutathione co-therapy slowed the progression of hearing loss and significantly attenuated the final threshold shift s by 20 to 40 dB. Morphological evaluation confirmed hair cell loss af ter gentamicin treatment and protection by glutathione. Drug serum lev els were assayed at 2 and 7 days of treatment. There were no differenc es between the gentamicin (mean = 183 mu g/ml; range, 90 to 300) and t he gentamicin/glutathione group (mean = 164 mu g/ml; range, 80 to 320) . Antimicrobial activity of gentamicin was tested against Staphylococc us aureus and Pseudomonas aeruginosa. A 30-fold molar excess of glutat hione did not influence the efficacy of gentamicin. These studies sugg est that glutathione protects against ototoxicity by interfering with the cytotoxic mechanism.