| PurposeIn order to highlight the protection effect of a -lipoic acid (LA) in different loses. This study was undertaken to investigate the relation between the mechanism of aminoglycoside (AmAn) ototoxicity and reactive oxide species (ROS) increasing lead to lipid peroxida -tion (LPO). At the same time of estimating the LA's security, we can provide the experimental basis for the potential clinical thera -peutic use of LA in the management of patients undergoing AmAn treatmentMaterials and Methods1. 105 healthy guinea pigs, initially weighing 250-350g, with normal Preyer s reflex, were entered into the study.2. Animals were randomly divided into seven groups, of fifteen each. Groups were as follows: groups I , neither received KM i.m. injection nor LA i.p. injection; group II, received KM 400mg/kg/day i. m. injection; group III, received LA 50mg/kg/day i. p. injection for;group IV, received KM 400mg/kg/day i.m. injection and LA 25mg/kg/day i.p. injection; group V, receiv-ed KM 400mg/kg/day i.m. injection and LA 37. 5mg/kg/day i.p. injection; groups VI, received KM 400mg/kg/day i.m. injection and LA 50mg/kg/day i. p. injection; group VII, received KM 400mg/kg/day i.m. injection and LA 75mg/kg/day i.p. injection .3. For each group, the experiment lasted for 7 days. Observed and recorded the animals" action everyday. Auditory sensitivity was monitored using auditory evoked brainstem response (ABR): perior to experiment(for the baseline ABR threshold) and at the end of experiment. On day 7, after the ABR recording, the animals of each group were decapitated and the cochleae were removed for scanning electron microscope(SEM) study (n=2)% cochlear surface preparations (n=8) and immuno histochemical method to measure the expressions of inducible notric oxide synthase (iNOS) (n=5). The cochlear surface was used to investigate superoxide dismutase (SOD), malondial dehyde (MDA), glutathione(GSH).4. All data were analyzed statistically by software SPSS10. 0.Results1. Normal ActionWe could observe the animals in group II were less action and appetite. The situation was serious increasely, went with i.m. injection KM continuely. There was no any change in the other groups.2. NO latencies of each wave and the threshold change were oberv- ed among group I , V~VII. That of group III and IV is statisticallysignificant higher than group I , V-VII, no statistically differencebetween them. That of group II is sta -tistically highest in the 7groups.3. Inner hair cell stereocilia and outer hair cell stereocilia relatively orderly arranged in group I , V-VII. In group II basal cochlear turn showed been damaged seriously: inner hair cell stereocilia and outer hair cell stereociliawere disarray -ed, missing, even loss of outer hair cell. In group III and IV, inner hair cell stereocilia and outer hair cell stereocilia were disarrayed, but no any missing, in the basal cochlear turn.4. In this study, cochlear SOD activity, GSH concentration were significant (P<0. 000) decreased in group IK IV, and the group II was the most; in the other hand, increased in group III. The cochlear MDA concentration changed in opposition to that. The activities of SOD and the concentrations of MDA and GSH were no statistically significant(P>0. 05) among group I , V-VII.5. The expression of iNOS in the cochlea of guinea pigs is greatest in group II, and is greater in group III, IV. In th group I , V~ VII, the expression is little, even no expression.Conclusion1. KM (400mg/kg/d) can impair both outer and inner hair cells in guinea pig's cochlea, by im, after 7 days.2. In guinea pig's cochlea AmAn can introduce intracellular ROS generation plentifully. Furthermore, ROS can impair it's antioxidant system and induce the lipid peroxidantion (LPO). That may be the part of the mechanism of the pathological injure of cochlea induced by AmAn.3. In the study, ABR can monitor the change of guinea pig's audition .4. LA is a powerful and lipophilic antioxidant which can attenuate the cochlear damage induced by a high...
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