An Experimental Study Of Acetamidophenol To The Mice’s Hearing Loss

Objectives: This thesis mainly discusses Acetamidophenol to the mice’s hearingdamage and the possible damage system, which can provide experimental bases for clinicalprevention and reduction of the misuse of acetaminophen the hearing decline caused.Methods:1.Establish the hearing damage model of Acetamidophenol to mice.Regardless of male and female mice, with the weight of20±2g each, healthy seven-year-oldC57mice were randomly divided into Acetaminophen low-dose group (150mg/(kg·d)、Acetaminophen medium-dose group、300mg/(kg·d)、 Acetaminophen high-dose group600mg/(kg·d)） and control group. Then mice were tested for ABR to observe the changesof ABR’s threshold in the zero, second, fourth and ninth day separately. The change ofcochlea hair cells morphology was studied by immunofluorescent labeling. And HPLCdetects the concentration of Acetaminophen in endolymph of mice cochlea.2.HPLC is usedto determine the mouse cochlea lymph to the concentration of Acetamidophenol. What’smore, Immunofluorescence is utilized to observe the morphology change of Cochlea haircells.3.Select20mice which are the same as C57mice. They are classified into normalgroup and experimental group. There are10mice in normal group, which are given salineorally0.2ml/day. By contrast, there are10mice in experimental group, which are givenorally acetaminophen300mg/(kg·d). After these two groups are fed for3days, acuteisolated active cochlear good IHCs, do the whole-cell patch-clamp technique cochlear IHCselectrophysiological changes.Results:1.After fed by Acetamidophenol for thirty minutes, the Acetaminophen inendolymph of mice cochlear can be detected. Endolymph to the drug concentration ofAcetaminophen has the positive relationship to feeding dose.2.As the time of givingmedicine to all the groups strengthens, the ABR thresholds heightens. After low-dose group,medium-dose group and high-dose group are given medicine for nine days, the averagethreshold is50±11dB in low-dose group,44±16dB in medium-dose group and55±17dB inhigh-dose group respectively. Compared with control group, there are significantdifferences (P<0.05).3.As the time of feeding strengthens, there emerges different levels ofloss.4.inner hair cells in the whole-cell patch-clamp technique in the experimental group compared with the normal group of inner hair cells calcium current decreases, the peakmembrane capacitance and membrane capacitance are reduced.Conclusions:1.Acetaminophen can enter into Cochlear lymph through Bloodlabyrinth barrier, which can directly have an influence on mice Corti’s organ and damagethe psychological function of inner and outer hair cells.2.after C57mice are fed byAcetaminophen, the ABR of C57mice has certain increase with the change of medicineconcentration. And the extent of damage was positively correlated to the dosage and thetime. Cochlea immunofluorescence shows that the cochlear hair cell damage toAcetaminophen C57mice’s hearing damage is stable.3.The mechanisms that cause hearingdamage by Acetaminophen have two aspects: a Acetaminophen can cause direct damage tothe inner hair cells; b Acetaminophen can induce the abnormal electrophysiological changesin cochlear hair cells of C57mice. Besides, inner hair cells Ica2+decrease and△Cmreduces, thus causing damage to hearing damage.