Effect Of Endotoxin On The Cochlea Of Guinea Pig And The Role Of Dexamethasone In Endotoxin-Induced Otitis Media

PurposeThe aims of this experiment are to study the mechanism of damage to cochlea of guinea pigs after tympanic cavities are inoculated lipopolysaccharide (LPS) and to investigate the effect of dexamethasone on the cochlea exposed to LPS in order to provide the theoretical basis for the clinical therapy of otitis media.Materials and MethodsSixty healthy guinea pigs, weighing from 300 to 400 g with normal Preyer's reflex, were randomly divided into 5 group. Group I (n=12), the normal control group. Group II(n=12), the saline control group. 50 i*l sterile saline was instilled into each tympanic cavity. Group III (n=12), the dexamethasone control group. 50 μL of 1 μ gl μl solution of dexamethasone was instilled into each tympanic cavity. Group IV (n=12), the endotoxin group. 50 μ I of 1 μ gl μ I solution of LPS was instilled into each tympanic cavity. Group V (n=12) , the dexamethasone therapy group. 50 μ I of 1μ gl μ I solution of LPS was instilled into each tympanic cavity, followed half an hour later, by 50 μI of 1 μl μ I solution of dexamethasone. Inner ear function of theall guinea pigs was assessed by auditory brainstem response ardiometry (ABR). ABR in group II - V was measured 48 hours after operation. The activities of superoxide dismutase (SOD) were meatureed in five animals of each group and the concentrations of nitric oxide (NO) were detected in the other five of the rest guinea pigs and two animals were used for morphologic study. The data were disposed by software SPSS 10.0.Results1. No latencies of wave I , wave II and the ABR threshold change were observed among the five groups, but in group IV they had elevatory tendencies compared with those in other groups. Statistically significant increase occured at the latency of wave III in group IV compared with those in other groups (P<0.05). The latency of wave IV and the interpeak latency of wave I-III were significantly greater in group IV than those in other control groups (P<0.05).2. The activities of SOD and the concentrations of NO were not significantly different among group I ~ III. The activities of SOD showed a significant decrease (P<0.05) and the concentrations of NO showed a significant increase in group IV compared with those in other groups (P<0.05). However, the activities of SOD and the concentrations of NO were significantly different in group V from those in other control groups (P<0.05).3. Inner hair cell and outer hair cell stereocilia in group I ~ III appeared nomal. Disarrangement of inner hair cell and outer hair cell stereocilia and loss of hair cells were seen in the basal turn of group IV . The damaging degree of outer hair cells aggravated gradually from the inner row to the outer row. In group V disorder of inner hair cell and outer hair cell stereocilia was relieved compared with group IV and loss of hair cells almost disappeared.Conclusion1. Endotoxin can cause damage to hair cells in guinea pigs following tympanic cavity administration.2. The enhanced contents of both superoxide anion and nitric oxide (NO) may be part of the mechanism of the pathological injury of the cochlea induced by LPS.3. Dexamethasone can effectively relieve damage to cochlea in LPS-mediated otitis media.