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@#The effect of sodium salicylate on the endogenous metabolism of hair cell-like cells (HEI-OC1).of mice was analyzed based on liquid chromatography-quadrupole time of flight mass spectrometry (LC-Q-TOF/MS).Firstly, HEI-OC1 cells were treated with different concentrations of sodium salicylate, and cell survival was examined by the CCK-8 method. Next, sodium salicylate was administered for different duration to observe the changes in cell morphology. Inter-group differential metabolites were screened out, and the associated metabolic pathways were analyzed based on metabonomic technology.Results showed that sodium salicylate could significantly inhibit the survival rate of HEI-OC1 cells, and that, as the concentration increased, the inhibitory effect became stronger. Also, the cell morphology could be elongated after administration and return to normal after withdrawal.Eighteen differential metabolites such as orotic acid, uridine and aspartic acid were screened out after treatment of sodium salicylate, which mainly involving two possible metabolic pathways, namely the metabolism of alanine, aspartic acid and glutamic acid, and that of pyrimidine.In summary, the application of metabolomics technology to evaluate the effect of sodium salicylate on hair cells from the microscopic perspective can provide new ideas for the study of sodium salicylate ototoxicity and development of tinnitus.
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OBJECTIVE To investigate dopamine level changes in the Nucleus Accumbens (NAc) of the limbic system by salicylate and the role of dopamine in the mechanisms of tinnitus.METHODS We recorded the change of dopamine before and after sodium salicylate injection in rats by microdialysis combined with electrochemical methodologies in the nucleus accumbens (NAc).RESULTS Salicylate produced significant increase in dopamine level in the NAc, to a maximum of (321±97)% of baseline and then remain stable. In contrast, saline only produced slight increase.CONCLUSION The increase of dopamine in the NAc may be related to the generation of tinnitus. The data in vivo provide direct evidence of the important role that the dopaminergic system plays in the generation of tinnitus.
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Objective To investigate the influences of sodium salicylate on the auditory brainstem response (ABR)and expression of EphA4mRNA in rat inferior colliculus and its effects on salicylate ototoxicity.Methods A total of 30 healthy SPF rats were randomly divided into five groups:the control group (without any treatment),S7 (i.m.injection of sodium salicylate,175mg/kg,twice daily for 7 days),S14(the same method as S7,twice daily for 14 days),S14+R14(the same method as S14,twice daily for 14 days and recovered for 14 days),and S14+R28(the same method as S14,twice daily for 14 days and recovered for 28 days).After the ABR assessment,rats were sacri-ficed after deep anesthesia and the inferior colliculus tissues were dissected.Real-time PCR was used to detect the expression of EphA4mRNA.Results Compared with the control group,ABR thresholds in the S7 group and S14 group were increased significantly (P0.05).The inferior colliculus EphA4mRNA expression level of S7 group was signifi-cantly decreased than the control group (P0.05).Conclusion Long term injection of sodium salicylate can cause changes in the inferior colliculus of EphA4mRNA which are related closely with synaptic plasticity.It may lead the alteration of the inferior colliculus synaptic plasticity,which is associated with the changes of the hearing failure and the tinni-tus behavior.This indicates that EphA4 which is considered as a related protein in the inferior colliculus may play an important role in the pathology of tinnitus.
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Objective To investigate the effect of electroacupuncture at different points on auditory brainstem response (ABR) in a rat model of sodium salicylate-induced tinnitus.Method Forty-one male Wistar rats were randomly allocated to saline control (saline), sodium salicylate model (SA), electroacupuncture at Tinggong+ Yifeng (EA), electroacupuncture at Waiguan+ Zhongzhu (AA) and electroacupuncture at Zusanli+ Sanyinjiao (LA) groups. The saline group consisted of five rats and each of the other groups, nine rats. The model was made by intraperitoneal injection of sodium salicylate 275 mg/kg. The saline control group was injected with a corresponding volume of saline. Various acupoint electroacupuncture groups were given electroacupuncture at bilateral Tinggong+ Yifeng, Waiguan+ Zhongzhu and Zusanli+ Sanyinjiao, respectively, at 30 min after model making. Electroacupuncture lasted 30 min. The ABRs were recorded before model making and once every one hour for five consecutive hours after model making. The stimulus sounds were short clicks and tone bursts of frequencies of 4, 8, 16 and 32 kHz. The ABR threshold was used as an assessment index.Results Under the condition of clicks, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the SA, EA, AA or LA group and the saline group (P<0.05), at two to five hours after model making between the EA or AA group and the SA group (P<0.05) and at one hour after model making between the LA and SA groups (P<0.05). Under the conditions of 4, 8 and 16 kHz, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the SA, EA, AA or LA group and the saline group (P<0.05). Under the condition of 32 kHz, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the SA, AA or LA group and the saline group (P<0.05). Under the condition of 4 kHz, there was a statistically significant difference in the ABR threshold at two to five hours after model making between the EA and SA groups (P<0.05) and at four to five hours after model making between the AA and SA groups (P<0.05). Under the condition of 8 kHz, there was a statistically significant difference in the ABR threshold at two to five hours after model making between the EA or AA group and the SA group (P<0.05). Under the condition of 16 kHz, there was a statistically significant difference in the ABR threshold at two, four and five hours after model making between the EA and SA groups (P<0.05). Under the condition of 32 kHz, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the EA and SA groups (P<0.05).Conclusion Electroacupuncture at both periauricular and forelimb points can improve the ABR threshold in sodium salicylate-treated rats. The effect of electroacupuncture at periauricular points is superior to that at forelimb points.
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Objective To study the expression of TrkB and c-fos in rat auditory cortex after long -term ad‐ministration of sodium salicylate and the mechanisms of salicylate ototoxiclty .Methods Normal adult rats were di‐vided into three groups :normal group without any treatment ,long -term treatment group given i .m .injections , 175 mg/kg ,twice daily at 9:00 am and 6 :00 pm for consecutive 14 days and the recovered group using the same method as the chronic group except that they were sacrificed 28 days after salicylate treatment ceased .After the de‐tection of ABR ,rats were sacrificed after deep anesthesia ,and the auditory cortexes were dissected rapidly .Real-time PCR and Western-blot were explored to detect the expression of TrkB and c-fos .Results The average ABR threshold of normal rats was 36 ± 2 .23 dB SPL .The average ABR threshold of long -term group was 41 .3 ± 3 .31 dB SPL ,which was significantly increased than normal group(P0 . 05) .The expression of c-fos mRNA(1 .24 ± 0 .09)and protein(0 .70 ± 0 .12)in the long -term group were signifi‐cantly increased ,when compared with the normal group .The c-fos mRNA(1 .23 ± 0 .04)and protein(0 .68 ± 0 .08) expression in the recovered group were also significantly increased compared with the normal group .The expression of TrkB mRNA(1 .26 ± 0 .10)and protein(1 .85 ± 0 .17)in the long -term group were significantly increased ,when compared with the normal group .The TrkB mRNA(1 .23 ± 0 .07)and protein(1 .80 ± 0 .08)expression in the recov‐ered group were also significantly increased compared with the normal group .Conclusion The inereased expression of c-fos in the long -term group may be related to the enhancement of central auditory function .The inereased ex‐pression of Trk-B in the long -term group might be involved in instability of synaptic plasticity in tinnitus .
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Objective To establish an animal behavioral model of tinnitus with step -down test ,and make use of the model to analyze the tinnitus genesis site in the salicylate-rats .Methods Forty wistar rats were includscl in this study ,they were randonly into 2 groups(experinent group and constrot group ,20 rats each group) .Ascertain that the animals treated with sodium salicylate(SS) have the sensation of tinnitus with the method of step -down test behavioral model .After having established a behavioral conditioned reflex ,subjects responded correctly to jump onto a climbing pole after hearing the sound .Then animals were under bilateral auditory nerves section ,to test whether the ablated-animals could still jump onto the pole after being treated with SS .Results Animals with the ab‐lating surgery could seldom jump onto the pole ,only reaching 1 .59 ± 0 .12 times average per 10 tests .Compared with con‐trol group ,there were significant differences with t-Test (P<0 .05) ,suggesting that subjects could not hear the tinnitus after the surgery .Conclusion Sodium salicylate could not make the animals with bilateral auditory nerves section to have the sensation of tinnitus .The peripheral auditory system plays an extremely important role in salicylate-induced tinnitus .
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Objective To investigate whether blocking NR2B receptor can reverse the process of cytotoxicity to spiral ganglion neurons induced by sodium salicylate in guinea pig by applying ifenprodil (a NR2B antagonist) at the round window niche .Methods Sixty healthy guinea pigs provided by the experimental animal center of Guangxi medical university were randomly and evenly divided into a control group (Group I ,no treatment) ,an APL group (Group II ,60μl APL directly applied to the round window ) ,a sodium salicylate group (Group III ,60 μl APL di-rectly applied to the round window and then be given intraperitoneal sodium salicylate injection ) ,and an ifenprodil group (Group IV ,60μl of 10μmol/l ifenprodil in APL directly applied to the round window and then be given intra-peritoneal sodium salicylate injection ) .Sodium salicylate was given at 400 mg · kg -1 · d-1 for 7 days .Auditory brainstem responses (ABRs) were recorded before animal sacrifice by decapitation .The left cochlea was removed and prepared for detection of caspase -3 expression in spiral ganglion neurons via immunohistochemistry .From each group ,6 cochleae were used to test apoptosis index in spiral ganglion neurons using the TUNEL technique .Results Before salicylate administration ,the ABR threshold was less than 40 dB SPL in all animals .After salicylate ad-ministration ,the ABR threshold was 33 .33 ± 5 .17 dB SPL in Group II ,64 .17 ± 7 .36 dB SPL in Group III and 49 .17 ± 5 .85 dB SPL in Group IV ,in contrast to 31 .67 ± 5 .16 dB SPL in Group I (controls) .The caspase -3 ex-pression was not changed obviously in Group I and Group II ,but was significantly changed in Group III and Group IV (P<0 .01) .The caspase-3 expression appeared to be decreased in Group IV compared to those in Groups III (P<0 .05) ,but still increased compared to those of in Group I and II (P<0 .05) .The apoptosis index among spiral ganglion neurons in Groups III and IV increased significantly compared to those of in Group I and II (P<0 .001) .It was however ,lower in Group IV than in Group III (P<0 .01) .Conclusion Blocking NR2B receptor with specificity can reverse the process of cytotoxicity to spiral ganglion neurons induced by sodium salicylate in guinea pig .
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Objective To observe the effects of long term injection sodium salicylate on the auditory brain-stem response(ABR)and expression of glutamic acid decarboxylase -67(GAD67) in rat inferior colliculus .Methods Eighteen healthy Wistar rats were randomly divided into three groups :the sodium salicylate group (intramuscular injection of 10% sodium salicylate ,175 mg/kg ,twice daliy for 28 days) ,the saline group (intramuscular injection with saline on same does at the same time) ,the control group (without any treatment) .The rats received ABR after modeling ,then were decapitated and inferior colliculus tissues were stripped .Western blot was used to study the dif-ferent expression of GAD67 protein levels in the three groups .Results Compared with the saline group and control group ,ABR thresholds of the sodium salicylate group were significantly elevated and latency of wave Ⅲ was aslo sig-nificantly prolonged(P0 .05) .The inferior colliculus GAD67 protein expression level of sodium salicylate group was significantly higher than the saline group and control group(P0 .05) .Conclusion Long term injection of sodium salicylate can cause a change in the inferior colliculus of GAD67 protein expression and the up regulation of GAD67 expression may occur as a com-pensatory response to increase inhibiting effect .The change of GAD67 protein expression is likely as a compensatory and regulatory mechanisms for sodium salicylate ototoxicity .
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Salicylate, the active ingredient of aspirin can cause sensorineural hearing loss and tinnitus when plasma concentrations reach a critical level. The ototoxic mechanisms of salicylate remain unclear but hearing and tinnitus usually recovers a few days after intoxication. There have been few reports of salicylate-induced ototoxicity in Korea, and the majority is caused by a low dose of aspirin. Herein, we report a case of sudden hearing loss and tinnitus after acute salicylate intoxication and review recent updates on salicylate ototoxicity.
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Aspirin , Hearing , Hearing Loss , Hearing Loss, Sensorineural , Hearing Loss, Sudden , Korea , Plasma , Sodium Salicylate , TinnitusABSTRACT
Background Heat shock proteins (HSPs) are highly conserved proteins that are induced in cells when confronted with a wide variety of proteotoxic stresses.HSP27 has a high degree of similarity with α-crystallin protein.The abnormality of HSP27 structure and expression are closely related to the formation of cataracts.Our previous study showed sodium salieylate has the protective effect on H2O2-induced lens damage.Objective This study was to investigate the roles of MAPK signal pathway in sodium salicylate-induced the expression of HSP27 in human lens epithelial cells (LECs) in vitro.Methods Human LECs were incubated in the fresh media containing sodium salicylate at different concentrations (0-55 mmol/L) for different times (1-5 hours) and allowed to be recovered in fresh medium without sodium salicylate for 1-24 hours with or without pretreatment with P38MAPK inhibitor (SB203580), ERK1/2 inhibitor (PD98059) and JNK/SAPK inhibitor ( SP600125). The expressions of P38MAPK, EBK1/2, JNK/SAPK, phosphorylated P38MAPK, phosphorylated ERK1/2, phosphorylated JNK/SAPK and HSP27 were detected by Western blot. HSP27 mRNA was detected by RT-PCR. The expression of HSP27 was also detected by immunohistochemistry. Results There was only weak expression of HSP27 in normal human LECs.After stimulation of 35-55 mmol/L sodium salicylate was removed and human LECs were cultured again for 6 hours,the expression of HSP27 in LECs were significantly increased ( F= 509. 953,P<0. 01). HSP27 was absent expressed in human LECs in 55 mmol/L sodium salicylate stimulation for 1-5 hours groups, but LECs were re-cultured for 3,6 hours after removed the stimulation, the expression of HSP27 was elevated (F = 452. 534, P<0. 01). Activation of P38 M APK occurred after sodium salicylate stimulation 30 minutes and 1 hour ( F = 865.68, P<0. 01). However, ERK 1/2 was expressed after sodium salicylate was eliminated for 1-6 hours ( F = 388.84, P<0. 01). JNK/SAPK was inactived by sodium salicylate. The expression of HSP27 could be down-regulated with the pretreatment of SB203580 and PD98059. Conclusion Sodium salicylatc can induce the expression of HSP27 in human (LECs) . The effects are mediated,at least in part ,through the activation of P38MAPK and ERK1/2 signaling pathway .
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Salicylates, such as aspirin, are considered the most commonly used medicine in Korea for its anti-inflammatory, anti-pyretic, and analgesic properties. In spite of its wide range of benefits, aspirin produces unwanted adverse effects such as mucosal bleeding in the gastrointestinal tract, renal and hepatic dysfunction, Reye's syndrome in children, and hypersensitivity reactions, etc. Aspirin can also induce ototoxicity, such as reversible hearing loss and tinnitus. The pattern of hearing loss is typically mild to moderate and bilaterally flat in the absence of preexisting hearing loss. Hearing usually recovers in 72 hours after medication. However, it's rare that salicylate-induced ototoxicity are encountered. So we present this case of bilateral hearing loss that occurred after salicylate intoxication with a review of relevant literature.
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Child , Humans , Aspirin , Ear, Inner , Gastrointestinal Tract , Hearing , Hearing Loss , Hearing Loss, Bilateral , Hearing Loss, Sensorineural , Hemorrhage , Hypersensitivity , Korea , Reye Syndrome , Salicylates , Sodium Salicylate , TinnitusABSTRACT
Objective To investigate the different expression levels of Na+ - K+ - 2Cl- co- transporter NKCC1 mRNA in the cochlea of rats after sodium salicylate injection and to explore the mechanism underlying the change of outer hair cells, induced by different salicylate administration. Methods Twenty-four normal adult rats were randomly divided into four groups with six rats in each group. Rats in control group,did not recieve sodium sa-licylate injection. The other three groups were acute group,chronic group,and recovered group according to the dif-ferent doses of sodium salicylate. The fluorescence quantitative PCR method was used to detect the expression levels of NKCC1 mRNA in the rat cochleas of the four groups. Results NKCC1 mRNA was expressed in all of the four groups. After sodium salicylate injection, the expressions of NKCC1 mRNA in chronic and recovered group were higher than that in control group(P<0.05). While the expression of NKCC1 mRNA in acute group was lower than that in control group(P(0. 05). Conclusion The expression of NKCC1 mRNA in the normal cochlea indicates that NKCC1 may play an important role in the maintenance of Cl- in the endolymph of the cochlea. The alteration of NKCC1 mRNA expression caused by sodium salicylate injection may lead to the change of the outer hair cell electro-motility.
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d that sodium salicylate can induce the expression of HSP27 in HLECs-B3. The effects are mediated, at least in part, through the activation of P38MAPK and ERK1/2 signaling pathway.
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Salicylate (aspirin) causes ototoxic side effects in some patients, such as bilateral mild to moderate sensorineural hearing loss and tinnitus although its ototoxic mechanisms still remain largely unclear. We report about one case with acute sensorineural hearing loss anf tinnitus after one week of low dose aspirin therapy. Audiogram revealed a mild sensorineural hearing loss at 35.0 dBHL in the right ear. Tinnitus became louder more and more, and sounded like a unilateral or bilateral high-pitch noise with each recurrence persisting for five minutes or longer. Audiologic problem of this case resolve within two or three days after the aspirin is discontinued. Generally, ototoxicity of salicylate manifests as bilateral, flat to high-frequency sensorineural hearing loss, and the risk of ototoxicity increases with higher doses and prolonged treatment course. But our case tend to suggest that symptoms of ototoxicity also might be occur in patients in even low dose salicylate with variable audiologic finding case tend to suggest that symptoms of ototoxicity also can occur in patients in even low dose salicylate use with variable audiologic finding. Further work on the relationships between plasma salicylate concentrations and ototoxicity is required.
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Humans , Aspirin , Atrial Natriuretic Factor , Ear , Hearing Loss, Sensorineural , Noise , Plasma , Recurrence , Sodium Salicylate , TinnitusABSTRACT
The effects of sodium salicylate on the expression of heat shock protein 27 (HSP27)during oxidative stress in tissue-cultured human lens epithelial cells were investigated. Cultured human lens epithelial cells (HLB-3) were divided into 3 groups: control group (group A), oxidation injury group (group B) and sodium salicylate group (group C). Apoptosis of human lens epithelial cells cultured in vitro was induced in the presence of 150 μmol/L H2O2. Cells viability and the expression of HSP27 were analyzed. Viability of the cells was measured by methyl thiazole tetrazolium (MTT)chromatometry. The expression of HSP27 in HLB-3 cells was detected by using immunohistochemistry and image analysis system. Sodium salicylate could induce the expression of HSP27, and the cells viability in group C was significantly higher than in group B (0.2667±0.01414 vs 0.2150±0.01080, P=0.012＜0.05). The average gray value of HSP27 in group B was less than that in group C (P=0.000＜0.05). The increased expression of HSP27 by sodium salicylate might play an important role in the protection of hydrogen peroxide-induced injury of human lens epithelial cells,suggesting that sodium salicylate could suppress, at least in part, the apoptosis of human lens epithelial cells.
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OBJECTIVE To understand what role of the L-type calcium channels play in the mechanism of salicylate-induced tinnitus. METHODS The effects of salicylate on L-type calcium channels in freshly dissociated inferior colliculus neurons of rats were studied using the whole-cell voltage clamp method. RESULTS Salicylate blocked L-type calcium channel current (ICa,L) in concentration-dependent manner. The half-blocking concentration of salicylate was 1.99 mmol/L. Salicylate did not affect the conductance-voltage curve and the steady-state activation curve of ICa,L, shifted the steady-state inactivation curve of ICa,L by about 8 mV in the hyperpolarizing direction, and delayed the recovery from inactivation of ICa,L. CONCLUSION Our results suggest that salicylate’s blocking of L-type calcium channels may contribute to salicylate-induced tinnitus by decreasing the release of ?-aminobutyric acid in the inferior colliculus.
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OBJECTIVE:To establish a method for simultaneous determination of the contents of three components in synthesis and actual satongfeng injection.METHODS:A flexible tolerance simplex method was used for multi-wavelength spectrophotometry with interval of 1nm in 258～290nm wavelenth,33 wavelenths were selected.RESULTS:The linear range and average recoveries rate of sodium salicylate,phenazone and caffeine were 0～42,0～12,0～6?g?mL-1 and(99.93?0.22)%,(99.85?0.24)% and(100.19?0.40)% respectively.All were agreed with those by standard method.CONCLUSIONS:This method is easy in operation,fast and reproducible,applicable to automatic analysis,and therefore can be used for the quality control of the preparation.
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Objective To study the change and the characteristics of distortion product otoacoustic emissions (DPOAE) of awake guinea pigs with the acute injection of sodium salicylate, and to investigate the ototoxicity of sodium salicylate to OHC. Methods With CELESTA 503 otoacoustic emission analyzer, DPOAE including DP-gram and DP-I/O function of awake guinea pigs were recorded.DPOAE were measared before and 2,4,8 h after acute injection of sodium salicylate or saline respectively. The data were analysed with SPSS 10.0.Results Acute sodium salicylate injection mainly caused the DPOAE amplitude and the I/O slope to reversibly decrease and increase respectively. The changes were largest 2 h after injection, and almost returned to normal level 8 h after injection. The differences between certain outcomes of DPOAE after and before injection were significant (P
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Objective To investigate the different expression levels of Na+-K+-2Cl-co-transporter NKCC1 mRNA in the cochlea of rats after sodium salicylate injection and to explore the mechanism underlying the change of outer hair cells,induced by different salicylate administration.Methods Twenty-four normal adult rats were randomly divided into four groups with six rats in each group. Rats in control group,did not recieve sodium salicylate injection. The other three groups were acute group,chronic group,and recovered group according to the different doses of sodium salicylate.The fluorescence quantitative PCR method was used to detect the expression levels of NKCC1 mRNA in the rat cochleas of the four groups.Results NKCC1 mRNA was expressed in all of the four groups.After sodium salicylate injection,the expressions of NKCC1 mRNA in chronic and recovered group were higher than that in control group(P
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Objective To investigate the antagonist effects of sodium salicylate(NaSA) on the cisplatin(CDDP) induced hearing impairment in guinea pigs.Methods 60 guinea pigs were randomly divided into four groups: ①CDDP +NaSA(50 mg/kg) group,②CDDP +NaSA(100 mg/kg) group,③CDDP +NaSA(150 mg/kg) group and ④CDDP +NS(normal saline) control group.Auditory brainstem response(ABR) and distortion product otoacoustic emission(DPOAE) were used to evaluate their effects on hearing threshold and DPOAE amplitudes.Results The ABR responses of groupsⅠ,Ⅱ and Ⅲ were significantly lower than in the control group(P0.05).The ABR responses for group Ⅰ were significantly higher than group Ⅲ(P