Expressions Of Rac1 In Normal And Aminoglycoside-induced Ototoxic Damaged Cochlea Of Guinea Pigs

ObjectiveTo investigate the expression of Rac1 in the guinea pig cochlea of gentamicin-induced ototoxic damage and prevention with antioxidant sodium salicylate, and to explore the roles of Rac1 in the ototoxic mechanism of aminoglycoside antibiotics.MethodsThirty healthy male guinea pigs were involved in this study. All the guinea pigs were randomly divided into 3 groups and received intraperitoneal injections according to their arranged group. GroupI (control), treated with normal saline for 7 days. Group II (GM), treated with gentamicin alone for 7 days. Group III (GM+SA), treated with gentamicin in combination with sodium salicylate for 7 days. Paraffin-embedded cochlear section with immunohistochemical staining was used for evaluation of Rac1 expression in the cochlea. The protein was extracted from the cochlea tissues, and Rac1 protein levels in the cochlea were detected by Western blot assay.Results(1)Immunohistochemistry. A slightly positive reaction for Rac1 staining was found in the cochlea of the control group, mainly shown in the cytoplasm and cytomembrane of ganglion and organ of Corti. A highly positive expression was shown in GM group. The extent of Rac1 expression of GM+SA group was between the control and GM group. Image analysis showed that the differences of Rac1 expression between each two groups were statistically significant (P < 0.05).(2)Western blot assay. Expression of Rac1 protein was highest in GM group and decreased in GM+SA group, while the intensity of Rac1 protein expression in GM+SA group was between the control and GM group. Statistics analysis showed that the expression between each two groups had significant difference (P < 0.05).ConclusionA slightly positive reaction for Rac1 staining was found in the cochlea of guinea pigs, mainly observed in the cytoplasm and cytomembrane of spiral ganglion and organ of Corti. With gentamicin administration, upregulation of Rac1 protein expression was shown in the cochlea. Simutaneous administration of antioxidant sodium salicylate could significantly decrease the expression of Rac1 protein. These results indicated that Rac1 may play an immportant role in the procession of gentamicin-induced oxidative damage of cochlea.