1.Attenuation of streptomycin ototoxicity by tetramethylpyrazine and its effect on K⁺ channels in the outer hair cells of guinea pig cochlea.
Hao TANG ; Gui-Ying CUI ; Li-Juan SHI ; Qing-Hua GAO ; Yu CAO
Acta Physiologica Sinica 2007;59(4):534-538
In order to elucidate the mechanism underlying the attenuation of streptomycin ototoxicity by tetramethylpyrazine (TMP), the present study investigated the effect of TMP on the outward K(+) current in the outer hair cells of guinea pig cochlea. Sixty guinea pigs were divided into 6 groups randomly. Auditory brainstem response (ABR) was used to observe the change in thresholds and to evaluate ototoxicity induced by streptomycin. Whole-cell patch-clamp technique was used to observe the effect of TMP on outward K(+) current in isolated outer hair cells. The results showed that TMP attenuated the threshold shift caused by streptomycin and increased the amplitudes of Ca(2+)-sensitive K(+) current [I(K(Ca))] in the outer hair cells. The present data suggest that TMP displays anti-ototoxicity induced by streptomycin. The augmented amplitudes of I(K(Ca)) of the outer hair cells induced by TMP may be one of the mechanisms underlying its ototoxicity-attenuating effect.
Animals
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Auditory Threshold
;
Cochlea
;
cytology
;
Evoked Potentials, Auditory, Brain Stem
;
Guinea Pigs
;
Hair Cells, Auditory, Outer
;
drug effects
;
Patch-Clamp Techniques
;
Potassium Channels
;
metabolism
;
Pyrazines
;
Streptomycin
;
toxicity
2.Effects of acetamidophenol on auditory in mice.
Lin CHEN ; Xiaoqin LUO ; Xiaohong CHEN ; Xueyuan ZHANG ; Wei YUAN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(11):785-789
OBJECTIVE:
The purpose of this investigation was to observe the effects of the Acetaminophen on auditory in mice.
METHOD:
Regardless of male and female mice, healthy seven-year-old C57 mice were randomly divided into Acetaminophen low-dose group (150 mg/kg), Acetaminophen medium-dose group (300 mg/kg), Acetaminophen high-dose group(600 mg/kg) and control group. Then mice were tested for ABR to observe the changes of ABR's threshold in the zero, second, fourth and ninth day separately. The change of cochlea hair cells morphology was studied by immunofluorescent labeling. And HPLC detects the concentration of Acetaminophen in endolymph of mice cochlea.
RESULT:
After 30 minutes following administration, the Acetaminophen in endolymph of mice cochlear can be assayed by high performance liquid chromatography (HPLC). Acetaminophen increased the hearing thresholds compared to the control group. Hearing thresholds increased significantly in the Acetaminophen at 9 d,compared to the control group (P < 0.05). After administered medium-dose and high-dose of Acetaminophen, on the 9th day with the time of giving medicine to all the groups strengthens, the ABR thresholds heightens. And the average threshold is (44.75 +/- 16.00) dB, (50.00 +/- 11.00) dB respectively. Hair cells damages could be observed in experimental group after operations.
CONCLUSION
Acetaminophen can pass through blood-labyrinth barrier to the inner ear. These data demonstrate that taking certain acetaminophen can induce hearing impairment in mice.
Acetaminophen
;
toxicity
;
Animals
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Female
;
Hair Cells, Auditory
;
drug effects
;
pathology
;
Hearing
;
drug effects
;
Male
;
Mice
;
Mice, Inbred C57BL
3.Effects of Erlong Zuoci pill and its disassembled prescriptions on gentamicin-induced ototoxicity model in vitro.
Yang DONG ; Bi-yin CAO ; Jing WANG ; Da-lian DING ; Zhi-fen HAN ; Jian-rong SHI
Chinese journal of integrative medicine 2010;16(3):258-263
OBJECTIVETo study the effects of Erlong Zuoci Pill (, ELZCP) and its disassembled: prescriptions on gentamicin (GM)-induced ototoxicity model in vitro.
METHODSAfter the spiral organ of cochleae: of newborn mice (postnatal days: 2-3) cultured for 24 h, GM alone or combined with water extracting-alcohol precipitating solution of ELZCP or with its disassembled prescriptions was added. Hair cells were observed under a fluorescence microscope after TRITC-phalloidin staining, and the cochlear hair cell loss rate was calculated by counting the whole cochlear hair cells and analyzed by whole cochlear hair cells analyzing software.
RESULTSGM induced cochlear outer hair cells (OHCs) and inner hair cells (IHCs) injuries in a dose-dependent manner, and they were significantly different as compared with those in the normal control group (P<0.05, P<0.01). ELZCP at the concentration of 0.003-3 mg/mL could decrease the hair cells loss induced by the 0.3 mmol/L GM (P<0.05, P<0.01), the effects was in a dose-dependent manner, and the concentration of 0.3 mg/mL showed the optimal protective effect. For the ELZCP disassembled prescriptions, Liuwei-Dihuang could decrease OHC loss rate than that in the 0.3 mmol/L GM model group (P<0.05), but the OHC loss rate was still higher than that in the ELZCP group (P<0.01), which indicated that the protective effect of hair cells by Liuwei-Dihuang was not better than that of ELZCP. Poria decreased OHC loss rate from 72.1 % +/-3.7 % to 58.8 %+/- 8.2 % (P<0.05).
CONCLUSIONSELZCP could play a role in antagonizing the injury of cochlear hair cells induced by GM ototoxicity,: and its disassembled prescriptions, Liuwei-Dihuang was the main component to protect the cochlear hair cells from GM-induced ototoxicity, and Magnetitum combined with Radix Bupleurui could strengthen the action of the whole prescription; Poria could reduce GM-induced OHC loss.
Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Gentamicins ; toxicity ; Hair Cells, Auditory, Inner ; drug effects ; pathology ; Hair Cells, Auditory, Outer ; drug effects ; pathology ; Mice ; Organ of Corti ; drug effects ; pathology ; Prescriptions ; Tablets
4.Effects of traditional Chinese herbs on growth of mouse hair follicles and hair bulb cells in vitro.
Qiao-yun WU ; Xian-jie WU ; Zhong-fa LU ; Min ZHENG
Journal of Zhejiang University. Medical sciences 2006;35(4):435-439
OBJECTIVETo investigate the effect of water soluble extracts of traditional Chinese herbs on growth of mouse hair follicles and hair bulb cells in vitro.
METHODSMouse hair follicles and hair bulb cells were cultured in Williams E medium with (experimental groups) or without (control group) water soluble extracts of Chinese herbs; the experimental group was further divided into mixture and single herb groups. Hair growth was observed by microscopy and growth activity of hair bulb cells was detected by MTT colorimetric assay.
RESULTOn day 7 of culture, the hair growth in the mixture groups was faster than that in the control group (P<0.05). On day 3 and 5 of culture, the cell growth activity in the mixture groups was greater than that in the control group (P<0.05). While the hair growth and the cell growth activity between the single herb groups and the control group were not significantly different.
CONCLUSIONThe water soluble extracts of mixed traditional Chinese medicines can promote the growth of mouse hair in vitro and stimulate the proliferation of hair bulb cells; while those of the single traditional Chinese herb have no effect.
Angelica sinensis ; Animals ; Animals, Newborn ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Hair ; drug effects ; growth & development ; Hair Cells, Auditory ; cytology ; drug effects ; Hair Follicle ; drug effects ; Mice ; Mice, Inbred C57BL ; Organ Culture Techniques
5.Preventive effects of cerebro cellular growth peptide on gentamycin-induced inner ear damage in guinea pigs.
Song-Jian KANG ; Xian-Jun SHI ; You-Zhen WEI ; An HONG ; Xin-Quan JIANG
Chinese Journal of Applied Physiology 2003;19(1):90-93
AIMTo investigate the preventive effects of the cerebro cellular growth peptide (CCGP) on gentamycin-induced inner ear damage in guinea pigs, and to clarify its mechanism.
METHODSThe hypoacusis severity and enzymatic activity in the cochlear hair cells were examined by brainstem auditory evoked potential (BAEP) and histochemistry, respectively. The damaged hair cells was counted in three groups.
RESULTSCCGP reduced the elevated BAEP reaction thresholds. It protected activities of mitochondrial succinate dehydrogenase and lysosome acid phosphatase in the cochlear hair cells. The number of damaged hair cells in the CCGP group was less than that in the gentamycin (GM) group.
CONCLUSIONCCGP can reduce GM ototoxicity. The mechanism may be associated with the protective activity of mitochondrial enzyme, the maintenance of lysosome intactness, energy metabolism of the cochlear hair cells, and reduction of autolysis of hair cells induced by hydrolase over flowing from lysosome.
Animals ; Evoked Potentials, Auditory, Brain Stem ; Female ; Gentamicins ; toxicity ; Guinea Pigs ; Hair Cells, Auditory ; drug effects ; physiology ; Male ; Nerve Growth Factor ; pharmacology
6.Gentamicin on inner hair cells ribbon synapses CaV1.3 calcium ion channel protein expression.
Jianhua SUN ; Xuefeng WANG ; Ke LIU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(4):261-264
OBJECTIVE:
To learn the influence the gentamycin on C57BL/6J mice hear and cochlear hair cell ribbon synapses CaV1.3 calcium protein amount. To explore the relationship between hear loss and its dosage correlation change and significance.
METHOD:
The fixed amino glucoside to C57BL/6J mice was used to make abdominal cavity injection mold every day. The auditory brain-stem response ABR was used to measure the hear of mice in 7th, 14th, 28th after the injection. Immunofluorescence method was used to observe cochlear basement membrane of hair ribbon synapse CaV1.3 calcium channel proteins in the distribution and expression. Inner hair cells synaptic membrane was immune fluorescent tags with CtbP2 and CaV1. 3.
RESULT:
With the growth of the injected drugs, ABR threshold increased,but all the hair cells and shape had no obvious change. However the amount of hair rib bon synapse CaV1.3 calcium ion channel proteins in the expression had significant differences (P < 0.01). CaV1.3 calcium ion channel proteins increased slightly lower than normal at 7th day, significantly decreased at 14th day, had increased, increased quantity compare with 14th day, but at 28th day after intraperitoneal injection of gentamicin.
CONCLUSION
The increasing,decreasing and increasing trend of cochlear hair cells CaV1.3 proteins in the environment of amino glucoside drug toxicity showed that the increase of hair ribbon synapse CaV1.3 proteins may have a compensatory effect on the drug toxicity. With the increase of the drug toxicity effect, this kind of decompensated function could be the listening decline, which may be one of the mechanism of damage to hearing.
Animals
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Calcium Channels, L-Type
;
metabolism
;
Evoked Potentials, Auditory, Brain Stem
;
Gentamicins
;
pharmacology
;
Hair Cells, Auditory, Inner
;
drug effects
;
metabolism
;
Mice
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Mice, Inbred C57BL
;
Proteomics
7.Research on the origin and ultrastructure microglia-like cell in SD rat Corti's organ after neomycin ototoxicity.
Yu-cheng WANG ; Zheng-min WANG ; Wei WEI ; Huawei LI ; Yunzhen SHEN ; Houyong LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(8):618-619
Animals
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Cell Line
;
Ear, Inner
;
cytology
;
drug effects
;
Female
;
Hair Cells, Auditory
;
drug effects
;
ultrastructure
;
Male
;
Neomycin
;
adverse effects
;
Rats
;
Rats, Sprague-Dawley
8.The effects of oxidative damage induced by organic oxidant t-BHP on cochlear hair cells.
Li-mei CHEN ; Xiao GUO ; Xu-dong LI ; Zhi WANG ; Yi-min LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(3):186-189
OBJECTIVETo establish the oxidative damage model of cochlea hair cells using organic oxidant t-BHP in vitro.
METHODSHEI-OC1 cells were exposed to t-BHP at 8 doses (30~4000 µmol/L) for 12 h. Trypan blue test was used to detected the cellular viability and MTT assay was utilized to measured the cellular proliferation. The intracellular ROS levels were determined by 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA).
RESULTSThe survival rates of HEI-OC1 cells started decrease significantly at the dose of 100 µmol/L t-BHP, the peak of decreased survival rates appeared at the doses of 200~800 µmol/L. The results of MTT assay demonstrated that 30 µmol/L t-BHP could promote cellular proliferation ability, when t-BHP concentrations were higher than 200 µmol/L, the cellular proliferation ability was inhibited. The results of DCFH-DA assay showed that there was no fluorescence in control group, the strong fluorescence was observed in positive control group, the weak fluorescence was observed in 30~50 µmol/L t-BHP groups, the bright fluorescence was observed in 100 µmol/L t-BHP group, still the stronger fluorescence was observed in 200~1000 µmol/L groups, but the cellular number decreased with the doses because of the lower cellular viability.
CONCLUSIONThe exposure to 100 µmol/L t-BHP for 12 h could simulate the oxidative damage induced by noise in cochlear hair cells.
Cell Survival ; Cells, Cultured ; Hair Cells, Auditory ; drug effects ; pathology ; Humans ; Noise ; adverse effects ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; analysis ; tert-Butylhydroperoxide ; toxicity
9.Ototoxicity of kanamycin sulfate in adult rats and its underlying mechanisms.
Zhi-Cun ZHANG ; Hong-Meng YU ; Quan LIU ; Jie TIAN ; Tian-Feng WANG ; Chui-Jin LAI ; Xiao-Ya ZHOU
Acta Physiologica Sinica 2011;63(2):171-176
The aim of the present study was to assess the ototoxicity of kanamycin sulfate (KM) in adult rats and its underlying mechanism. Forty male Sprague-Dawley rats (6-7 weeks old) were randomly divided into the experimental group and the control group. The animals in the experimental group were injected subcutaneously with KM (500 mg/kg per day) for two weeks, and the control group received equal volume of normal saline. To assess the ototoxicity of KM, the auditory brainstem response (ABR) was recorded to monitor the changes in hearing thresholds, and the density of spiral ganglion cells (SGCs) and morphology of cochlea were observed using surface preparations and frozen sections of cochlea. The results showed that the hearing threshold of rats in the experimental group was elevated by more than 60 dB across all the frequencies two weeks after the first administration of KM. And in the experimental group, the density of SGCs became lower, and organ of Corti suffered loss of hair cells. The loss of outer hair cells (OHCs) was more severe than that of inner hair cells (IHCs), correlated with the density decrease of SGCs. We conclude that the ototoxicity of KM in the adult rats was apparent and the underlying mechanism is associated with the loss of SGCs and hair cells.
Animals
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Cochlea
;
drug effects
;
pathology
;
Evoked Potentials, Auditory, Brain Stem
;
drug effects
;
Hair Cells, Auditory, Outer
;
cytology
;
drug effects
;
pathology
;
Hearing Loss
;
chemically induced
;
physiopathology
;
Kanamycin
;
toxicity
;
Male
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Spiral Ganglion
;
pathology
;
physiology
;
ultrastructure
10.Observation on acupuncture at "Neitinggong" for antagonisting ototoxicity caused by gentamicin.
Wei-jun MA ; Min XU ; Xiao-tong ZHANG ; Hui LIU ; Hong-yue LI ; Xiao-hong ZHOU
Chinese Acupuncture & Moxibustion 2007;27(3):209-212
OBJECTIVETo explore the effect of acupuncture at "Neitinggong" drug-induced deafness.
METHODSGuinea pig deafness model was prepared by injection of gentamicin (GM). Acupuncture was respectively given at the points "Neitinggong" "Tinggong" (SI 19) and non-acupoints on the auricle in the experimental animals in different groups and the effects of different points on the auditory brainstem response and cochlear hair cells were observed.
RESULTSThere was a significant difference between GM group and Neitinggong group, and between GM group and Tinggong group. There was no significant difference between GM group and the auricle group, and between Neitinggong group and Tinggong group.
CONCLUSIONAcupuncture at "Neitinggong" can strength the function of the internal ear, and relieve the injury of cochlear hair cells caused by gentamicin, which is an effective acupoint for treatment of drug-induced deafness.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Anti-Bacterial Agents ; toxicity ; Cochlea ; drug effects ; pathology ; Deafness ; chemically induced ; prevention & control ; Evoked Potentials, Auditory, Brain Stem ; drug effects ; Female ; Gentamicins ; toxicity ; Guinea Pigs ; Hair Cells, Auditory ; drug effects ; pathology ; Male