Apoptosis And Caspase-3Expression Of Spiral Ganglion Cells In Guinea Pig’s Cochlea With Cisplatin.Nedapiatin.Oxaliplatin Ototoxicity

Background and purpose:platinum drugs so far the most widely used anticancer drugs. Based on the widely used and good efficacy of cisplatin.nedaplatin,.oxaliplatin in the treatment of head and neck cancer, treatment toxicity has also become a major consideration for the choice of drugs. The main common toxicity of platinum drugs: liver toxicity, kidney toxicity, blood toxicity, ototoxicity (drug toxicity and different emphasis). Recent renal toxicity of platinum drugs have a certain protective measures, but the for ototoxicity control means is relatively backward, one of the reasons is that the mechanism of the ototoxicity of platinum drugs is not very clear, ototoxic mechanism of platinum drugs and ototoxicity size and little[5].Depth of the mechanism of toxicity of platinum drugs ear protection for its ototoxicity provide new ideas, and may provide the basis for the clinical selection of the application of cisplatin, nedaplatin and oxaliplatin in ototoxicity. We refer to the cisplatin-induced mechanism of apoptosis induced ototoxicity research methods, nedaplatin, oxaliplatin induced spiral ganglion cell apoptosis and caspase-3activation studies and contrast, aims to cisplatin, nedaplatin, oxaliplatin ototoxic mechanism to explore and compare the size of the ototoxicity.Methods:First, take the30normal albino young guinea pigs worked out to establish the appropriate dose of in vivo ototoxicity model and then, take the48normal hearing young albino guinea pigs were randomly divided into control group, cisplatin, nedaplatin group, Oxaliplatin group; packet injection foregoing worked out a molar three platinum-based chemotherapy drugs, the control group injected with saline, changes in the number of apoptotic cells detected by TUNEL method, each group of spiral ganglion cells detected by immunohistochemical method caspase-3expression. TUNEL slice observe the apoptotic index (AI), caspase-3slices observed immunohistochemical positive index (AIOD=positive area than×OD value). Group and between groups of data using Microsoft Excel2000software package, single-factor analysis of variance; results are the mean±standard deviation (x±s), respectively, P<005and P<001as a significant judgment criteria.Results:1.Establish in vivo ototoxicity model suitable molar cisplatin, nedaplatin, oxaliplatin dose were12.5mg/kg,12.6mg/kg,16.6mg/kg.2. analysis of data obtained1) cisplatin spiral ganglion cells with similar experimental results in line with this dose taken cochlear ototoxicity model tissue sections for apoptosis detection and caspase-3immunohistochemical staining.2), in the molar Nedaplatin group of guinea pig cochlea spiral ganglion cells by TUNEL staining cell count significantly increased caspase-3immunohistochemical staining in the detection of spiral ganglion cells, a positive result, indicating that the SGC apoptosis caspase-3activation, compared with the control group was statistically significant.3) the oxaliplatin group of spiral ganglion cells by TUNEL staining cell count increased slightly, then caspase-3immunohistochemical staining was positive in the detection of spiral ganglion cells is not obvious, no statistical significance compared with the control group.4) with cisplatin and nedaplatin group showed no statistically significant.Conclusion:In the control group and experimental group, caspase-3expression of TUNEL-positive cells appear consistent. Cisplatin compared with the control and nedaplatin group, the apoptosis and caspase-3positive expression than the control group compared with the significant difference, suggesting that caspase-3-mediated signal transduction mechanisms may be involved in of CDDP, NEDP-induced cochlear cell apoptosis process and lead to the occurrence of ototoxicity, experimental results provide a theoretical basis to achieve effective protection of CDDP, NEDP ototoxicity clinical. However, no significant difference between the two groups failed to prove that cisplatin ototoxicity is higher than nedaplatin. Oxaliplatin group no cells were apoptosis, because1) the inner ear lower toxicity,2) metabolism in the inner ear are very different dynamics and cisplatin (5mg/kg cisplatin the AUC curve and16.6mg/kg oxaliplatin AUC curves),3) live animals Ototoxicity model to establish a presence more difficult (to produce the inner ear toxicity prior to death) because of other systemic side effects. The Ototoxicity mechanism needs further study, and recommend that future research may consider in vitro cellular level model in order to study [15].