Objective: To study the prevention of gentamicin(GM) ototoxicity by deferoxamine(DFO) in the guinea pig.
Methods: Guinea pigs were randomly assigned to three experimental groups (GM-treated alone, DFO-treated alone, GM and DFO in combination) and one control group. Acoustic brainstem response (ABR), the surface preparation and transmission electron microscopy were utilized to evaluate the hearing thresholds and the cochlear morphology. To explore the mechanism associated with deferoxamine protection, serum levels of GM, BUN and Cr, together with concentration of MDA, SOD and iron in cochlear and renal tissues were measured.
Results: The GM group developed up to 40-60 dB of the threshold shifts at 8 kHz while the GM + DFO group developed only 15-25 dB of the threshold shifts (P < 0.05). Moorphological changes were consistent with functional changes. DFO did not alter serum levels of GM. Renal function of GM group was damaged obviously. However, changes of MDA, SOD and iron were not significant (P > 0.05). MDA and iron concentrations in cochlear tissue of the GM + DFO group were significantly lower than those in the GM group (P < 0.05) while SOD level was much higher than that in GM group.
Conclusion: This study suggests that free radical and iron involve in GM ototoxicity and DFO may become a promising therapeutic agent that can be used to reduce gentamicin ototoxicity.