Experimental Studies On Mechanism Of Gentamicin Ototoxicity And Preventing Its Ototoxicity By Sodium Salicylate

Aminoglycoside antibiotics (AmAn) are effective drugs in therapy against gram-negative infections, but the ototoxicity and nephrotoxicity limit their use in clinic. There aren't effective methods to prevent the toxicity to date because of unclear mechanism. Gentamicin is one of the most used AmAn, in our studies, we investigated the mechanism of gentamicin ototoxicity in several aspects; whether sodium salicylate can prevent its ototoxicity; and the ototoxicity of salicylate gentamicin.1. Detecting free radical in the cochlea induced by gentamicin and gentamicin+ sodium salicylate with electron paramagnetic resonanceElectron paramagnetic resonance (EPR) and DMPO(a trapping agenf) were used to detect hydroxyl radical in the cochlea explanted from guinea pigs which received gentamicin and gentamicin+ sodium salicylate. Results: After gentamicin administration, the signal increased significantly(P<0.05); when sodium salicylate was injected along with gentamicin, the signal reduced(P<0.05). Conclusion: Gentamicin administration results in increment of hydroxyl radical in the cochlea of guinea pigs, sodium salicylate can inhibit this increment.2. Gentamicin induced expression of nitric oxide synthase in cochlea and nitric oxide enhanced the ototoxicity of gentamicin...