Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coenzyme Q10 (CoQ10) has already been favorably evaluated in the clinical treatment of heart disease. In the otolaryngological field, it has been reported that CoQ10 is effective in promoting recovery from acute sudden deafness. However, the pharmakinetics of CoQ10 in the inner ear is not yet clarified. The present study focuses upon the pharmacokinetics of CoQ10 using guinea pigs with acute sensorineural hearing loss artificially induced by hypoxia conditions. The respiration of the animals was controlled in an artificial respirator while the ABR, ECG and blood pressure were monitored. Repeated hypoxia caused a gradual disappearance of the ABR. After the experiments, the animals were sacrificed and brain and inner ear were examined by histological and histochemical methods as well as by SEM and TEM. The results indicated that CoQ10 is effective in promoting recovery from damage in auditory hairs as well as preventing respiratory metabolic impairment of hair cell due to hypoxia.
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PMID:Pharmacokinetics of coenzyme Q10 in recovery of acute sensorineural hearing loss due to hypoxia. 324 40

Forty-five guinea pigs were randomly divided into 2 groups: 15 in the control group and 30 in the experimental group. All animals were injected immediately with 400 mg/kg kanamycin for 10 days. At the same time, the experimental animals were given orally 10 mg/kg thyroxin every other day 5 times. All animals were decapitated 10 days after administration of drugs and measurement of ABR. Then, the specimens of cochlea were prepared for both SEM and TEM. The result of SEM showed that the degeneration and loss of stereocilium in each turn was significantly milder in the experimental group than in the control. Under TEM, outer and inner hair cells showed changes caused by kanamycin. In the experimental group, the mitochondrias were basically normal. The secondary lysosomes gathered under cuticular plate and supranuclear area. In the control group, the mitochondria showed pyknosis and high density, and multivesicular bodies were increased. The cytoplasm was swelling. There were many vacuoles produced by accumulation of liquid in the cytoplasm. Based on the findings of ultrastructural changes of cochlear hair cells, the mechanism of thyroxine against ototoxicity of kanamycin was discussed.
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PMID:[An electron microscopic study of thyroxine against ototoxicity of kanamycin]. 803 86

Macroautophagy/autophagy dysfunction is associated with many neurodegenerative diseases. TFEB (transcription factor EB), an important molecule that regulates lysosomal and autophagy function, is regarded as a potential target for treating some neurodegenerative diseases. However, the relationship between autophagy dysfunction and spiral ganglion neuron (SGN) degeneration and the role of TFEB in SGN degeneration has not yet been established. Here, we showed that in degenerated SGNs, induced by sensory epithelial cell loss in the cochlea of mice following kanamycin and furosemide administration, the lipofuscin area and oxidative stress level were increased, the nuclear-to-cytoplasmic TFEB ratio was decreased, and the late stage of autophagic flux was impaired. After autophagy dysfunction was partially ameliorated with an MTOR inhibitor, which promoted TFEB translocation into the nucleus from the cytoplasm, we found that the lysosomal deficits were significantly relieved, the oxidative stress level was reduced, and the density of surviving SGNs and auditory nerve fibers was increased. The results in the present study reveal that autophagy dysfunction is an important component of SGN degeneration, and TFEB may be a potential target for attenuating SGN degeneration following sensory epithelial cell loss in the cochlea of mice. Abbreviations: 3-NT: 3-nitrotyrosine; 4-HNE: 4-hydroxynonenal; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ABR: auditory brainstem response; APP: amyloid beta (A4) precursor protein; CLEAR: coordinated lysosomal expression and regulation; CTSB: cathespin B; CTSD: cathespin D; SAMR1: senescence-accelerated mouse/resistance 1; SAMP8: senescence-accelerated mouse/prone 8; MAPK1/ERK2: mitogen-activated protein kinase 1; MTOR: mechanistic target of rapamycin kinase; SGN: spiral ganglion neuron; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscope; TFEB: transcription factor EB.
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PMID:Restoring autophagic flux attenuates cochlear spiral ganglion neuron degeneration by promoting TFEB nuclear translocation via inhibiting MTOR. 3070 60