Investigation Of Roles Of NAC In The Cochlear After Gentamicin Ototoxicity

Objective: To investigate the Gentamicin ototoxicity and the effect ofN-acetylcysteine (NAC) in the damage of cochlea.Methods: Sixty healthy Wistar rats were divided into the normal group, the controlgroup, medicine damage group and group after the intervention of NAC-1/-2.Group of Gentamicin ototoxicity: peritoneal injection of Gentamicin120mg/kg/d for 14 days; the control group: peritoneal injection of tales dosesSodium Chloride; group of NAC intervention-1: give NAC 350mg/kg 1 hour beforeperitoneal injection of Gentamicin; group of NAC intervention-2: give NAC for 14days the day after the finish of Gentamicin. Detect the ABR before the administrationand 24 hours after the last administration and make an analysis. The histomorphologyof cochlea was observed with hemotoxylineosin (HE) staining. The NF-κB and TNF-αimmunoactivity in cochlea was studied by immunohistochemisty and labelingratio of nuclear factor-kappa B (NF-κB) and tumor necrosis factor-α(TNF-α)expression was studied by image analysis.Results: The results of ABR showed that the threshold of group of Gentamicinototoxicity was 34.6986±11.5396, the NAC intervention-2 was 21.7373±9.9248, therewas significant difference with the normal group (5.8426±0.7775) (P＜0.05). TheNAC intervention-1 was 11.5102±5.4074 and the control group was 6.1552±0.9489,both had significant difference with the NAC intervention-2 and the group ofGentamicin ototoxicity (P＜0.05), no significant difference with the normal group(P＞0.05).HE staining showed there were lesions of hair cells in the Gentamicin ototoxicitygroup;Compare with the group of Gentamicin ototoxicity,groups after theintervention of NAC have a less cytomorphosis,defect and thinner stria vascularis.There was slight positive expression of NF-κB and TNF-αin the hair cell, thestria vascularis, the spiral ligament, the membrane spiralis, the endothelial lining ofcochlear glomeruli and the spiral ganglion. In the Gentamicin ototoxicity groups, atthe same time, the expression of NF-κB and TNF-αin the stria vascularis, thespiral ligament and cochlear glomeruli increased significantly. NAC could inhibitsuch expression obviously.Conclusion: We can establish the model of Gentamicin ototoxicity in cochlea ofWistar rats by peritoneal injection of Gentamicin. NF-κB and TNF-αmay lead to the cochlea lesions in the Gentamicin ototoxicity together; NAC may inhibit suchlesions by restraining the production of oxygen free radicals, and the earlier the better.