Protective Effect Of Deferoxamine And Ginkgo Biloba Extract (EGb) On Ototoxicity Of Cisplatin

Objective : The protective effect of iron chelator(Deferoxamine,DFO) and Extract of Ginkgo Biloba leavesInjection (EGb) against ototoxicity of cisplatin (CDDP) wasstudied by the test of auditory brainstem response (ABR),thevitality of superoxide dismutase (SOD) in serum,the content ofthe metabolite of lipid peroxidation (MDA) in serum, andobservesion of morphological change in hair cells with lightmicroscope,scanning electron microscope. Methods : Forty purebred guinea pigs which weremature,healthy,sensitive to auricle reflex,300-400 gram.The sexof them was not limited.They were randomly divided into fivegroups.Each group had eight guinea pigs.They were CDDPgroup,EGb group,DFO group,EGb+DFO group and controlgroup.GroupⅠreceived 2 mg·kg-1·d-1 CDDP transperitoneallyfor five days.Group Ⅱ received 14 mg·kg-1·d-1 EGb twodays before 2 mg·kg-1·d-1 CDDP transpeiitoneally for sevendays.Group Ⅲ received 100 mg · kg-1 · d-1 DFO bysubcutaneous injection on the bosom of thigh one hour before 2mg·kg-1·d-1 CDDP transpritoneally for five days.Group Ⅳreceived 14 mg·kg-1·d-1 EGb two days before DFO andCDDP.Then it was added 100 mg·kg-1·d-1 DFO one hour before 4英 文 摘 要2 mg · kg-1 · d-1 CDDP for five days.Group Ⅴ recivedphysiological saline(0.9%) transpritoneally for fivedays.Auditory threshold was tested before the experiment andafter it.The next day,blood samples were obtained and all theanimals were sacrificed. The vitality of superoxide dismutase(SOD) and the content of the metabolite of lipid peroxidation(MDA) were tested in serum. Cochleas were stripped and fixedby fixing solution.Light microscope observation:killedanimals,segregated otocyst from temporal bone quickly,exposedcochlea,bored apical cochlea,took stapes out,unpacked ovoidwindow and round window,poured cochlea with 4%Polyoxymethylene (4 ℃ ,PH=7.4) and fixed in it for oneday,washed with 0.1M PBS (PH=7.4),decalcificated with 10%Calcium Disodium Versenate for 20 days,washed withPBS;embedded with petroline,used paraffin sectioning methodwhich direction was paralled with modiolus,usedhaematine-eosin stain and marrow iron stain,observed with lightmicroscope. Scanning electron microscope observation:killedanimals,segregated otocyst from temporal bone quickly,exposedcochlea,bored apical cochlea,took stapes out,unpacked ovoidwindow and round window,poured cochlea with 2.5% GlutaricDialdehyde (4℃,PH=7.4) and fixed in it for 4-6 hours.Cochleashell and spiral ganglion were stripped and basilar membranewas exposed thoroughly under anatomical microscope.Theywere postfixed with 0.1% Osmium tetraoxide for 2hours;washed with 0.1 mol/l PBS for 1 hour, dehydrated 5英 文 摘 要gradiently with alcohol,transited with acetate isoamyl ester,driedat critical point,sputtered with golden ion,observed withSEM.Data were analysized by SPSS. Results : the hearing threshold of ABR was highersignifitcantly in CDDP group than in other groups (P<0.01) Thedifference of auditory threshold value between EGb group andcontrol group was significant (P<0.05).And the difference ofauditory threshold betweenⅡ,Ⅲ,Ⅳ groups and control groupwere not significant (P>0.05).The SOD in serum showed thatdifference between CDDP group and other groups wassignificant(P<0.01),while insignificant among othergroups(P>.05).The vitality of SOD was decreased obviously inCDDP group.The content of the metabolite of lipid peroxidation(MDA) in cochlea was higher significantly (P<0.01) in CDDPgroup than that in other groups.But the content of MDA in othergroups were not raised significantly (P>0.05).Light microscopeshowed that the spiral organ in CDDP group was distortedserviously.The outer hair cells swelled,modificated,displacedand the corti tunnel was broadened.Further more ,lytic necrosishappe...