Protective effect of creatine on amikacin-induced ototoxicity. 2022

Emre Apaydın, and Elif Dağlı, and Sevinç Bayrak, and Ekrem Said Kankılıç, and Hasan Şahin, and Aydın Acar
Kecioren Training and Research Hospital, Department of Otolaryngology, Ankara, Turkey. Electronic address: dr.emreapaydin@hotmail.com.

BACKGROUND Aminoglycosides are widely known for their ototoxic side effects. Nevertheless, they are potent antibiotics used in the treatment of life-threatening conditions because of the current concern for antibiotic resistance. We hypothesized that creatine supplements which are believed to improve mitochondrial antioxidant defense system and maintain optimal energy homeostasis may improve the ototoxic side effects. OBJECTIVE This study aimed to investigate the protective effects of creatine monohydrate against ototoxicity induced by amikacin in rats in an experimental animal model, using distortion product otoacoustic emissions and auditory brainstem response. METHODS Twenty healthy rats were assigned to four groups (5 rats in each): the control group, the creatine monohydrate group, the amikacin group and the amikacin+creatine monohydrate group. The creatine monohydrate group received creatine at a dose of 2g/kg once daily via gastric gavage for 21 days. The amikacin group received amikacin at a dose of 600mg/kg by intramuscular injections once daily for 21 days. The amikacin+creatine monohydrate group received intramuscular injections of amikacin (600mg/kg) once daily for 21 days and creatine monohydrate (2g/kg) once daily via gastric gavage for 21 days. The control group received nothing. The distortion product otoacoustic emissions and auditory brainstem response measurements were performed on all rats on days 0, 7, 21. RESULTS Regarding auditory brainstem response values, a significant increase in the auditory threshold was observed in the amikacin group on day 21 (p< 0.001). The amikacin+creatine monohydrate group showed significantly lower levels of auditory brainstem response auditory thresholds on day 21 in comparison to the amikacin group (p< 0.001). Additionally, the control group and the amikacin+creatine monohydrate group did not differ significantly with respect to auditory brainstem response thresholds on treatment day 21 (p> 0.05). When we compare distortion product otoacoustic emissions values, there was no significant difference between the amikacin and amikacin+creatine monohydrate groups on day 7 (p> 0.05), However significantly greater distortion product otoacoustic emissions values were observed in the amikacin+creatine monohydrate group on day 21 compared to the amikacin group (p< 0.001). CONCLUSIONS Our findings demonstrate that creatine treatment protects against amikacin ototoxicity when given at a sufficient dose and for an adequate time period.

UI MeSH Term Description Entries
D003401 Creatine An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.
D000081015 Ototoxicity Damage to the EAR or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION. Auditory Toxicity,Drug-Induced Cochlear Toxicity,Drug-Induced Cochleotoxicity,Drug-Induced Otological Toxicity,Drug-Induced Ototoxicity,Drug-Induced Vestibular Toxicity,Drug-Induced Vestibulotoxicity,Drug-Related Cochlear Toxicity,Drug-Related Cochleotoxicity,Drug-Related Otological Toxicity,Drug-Related Ototoxicity,Otological Toxicity,Radiation-Induced Ototoxicity,Cochlear Toxicities, Drug-Induced,Cochlear Toxicities, Drug-Related,Cochlear Toxicity, Drug-Induced,Cochlear Toxicity, Drug-Related,Cochleotoxicities, Drug-Induced,Cochleotoxicities, Drug-Related,Cochleotoxicity, Drug-Induced,Cochleotoxicity, Drug-Related,Drug Induced Cochlear Toxicity,Drug Induced Cochleotoxicity,Drug Induced Otological Toxicity,Drug Induced Ototoxicity,Drug Induced Vestibular Toxicity,Drug Induced Vestibulotoxicity,Drug Related Cochlear Toxicity,Drug Related Cochleotoxicity,Drug Related Otological Toxicity,Drug Related Ototoxicity,Drug-Induced Cochlear Toxicities,Drug-Induced Cochleotoxicities,Drug-Induced Otological Toxicities,Drug-Induced Ototoxicities,Drug-Induced Vestibular Toxicities,Drug-Induced Vestibulotoxicities,Drug-Related Cochlear Toxicities,Drug-Related Cochleotoxicities,Drug-Related Otological Toxicities,Drug-Related Ototoxicities,Otological Toxicities, Drug-Induced,Otological Toxicities, Drug-Related,Otological Toxicity, Drug-Induced,Otological Toxicity, Drug-Related,Ototoxicities,Ototoxicities, Drug-Induced,Ototoxicities, Drug-Related,Ototoxicities, Radiation-Induced,Ototoxicity, Drug-Induced,Ototoxicity, Drug-Related,Ototoxicity, Radiation-Induced,Radiation Induced Ototoxicity,Radiation-Induced Ototoxicities,Toxicity, Otological,Vestibular Toxicities, Drug-Induced,Vestibular Toxicity, Drug-Induced,Vestibulotoxicities, Drug-Induced,Vestibulotoxicity, Drug-Induced
D000583 Amikacin A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics. A.M.K,Amikacin Sulfate,Amikacina Medical,Amikacina Normon,Amikafur,Amikalem,Amikason's,Amikayect,Amikin,Amiklin,Amukin,BB-K 8,BB-K8,Biclin,Biklin,Gamikal,Kanbine,Oprad,Yectamid,BB K 8,BB K8,BBK 8,BBK8,Medical, Amikacina,Normon, Amikacina,Sulfate, Amikacin
D000617 Aminoglycosides Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS. Aminoglycoside
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D016057 Evoked Potentials, Auditory, Brain Stem Electrical waves in the CEREBRAL CORTEX generated by BRAIN STEM structures in response to auditory click stimuli. These are found to be abnormal in many patients with CEREBELLOPONTINE ANGLE lesions, MULTIPLE SCLEROSIS, or other DEMYELINATING DISEASES. Acoustic Evoked Brain Stem Potentials,Auditory Brain Stem Evoked Responses,Brain Stem Auditory Evoked Potentials,Evoked Responses, Auditory, Brain Stem,Acoustic Evoked Brain Stem Potential,Acoustic Evoked Brainstem Potential,Acoustic Evoked Brainstem Potentials,Auditory Brain Stem Evoked Response,Auditory Brain Stem Response,Auditory Brain Stem Responses,Auditory Brainstem Evoked Response,Auditory Brainstem Evoked Responses,Auditory Brainstem Responses,Brain Stem Auditory Evoked Potential,Brainstem Auditory Evoked Potential,Brainstem Auditory Evoked Potentials,Evoked Potential, Auditory, Brainstem,Evoked Potentials, Auditory, Brainstem,Evoked Response, Auditory, Brain Stem,Evoked Response, Auditory, Brainstem,Evoked Responses, Auditory, Brainstem,Auditory Brainstem Response,Brainstem Response, Auditory,Brainstem Responses, Auditory,Response, Auditory Brainstem,Responses, Auditory Brainstem
D017084 Otoacoustic Emissions, Spontaneous Self-generated faint acoustic signals from the inner ear (COCHLEA) without external stimulation. These faint signals can be recorded in the EAR CANAL and are indications of active OUTER AUDITORY HAIR CELLS. Spontaneous otoacoustic emissions are found in all classes of land vertebrates. Spontaneous Otoacoustic Emissions,Otoacoustic Emission, Spontaneous,Spontaneous Otoacoustic Emission
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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