Safety and Otoprotection of Metformin in Radiation‐Induced Sensorineural Hearing Loss in the Guinea Pig

Mujica‐Mota, Mario A.; Salehi, Pezhman; Dević, Slobodan; Daniel, Sam J.

doi:10.1177/0194599814521013

Cited by 20 publications

(13 citation statements)

References 32 publications

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“… 2 , 3 , 4 , 5 , 6 Regulators, such as p53, reactive oxygen species and c-Jun N-terminal kinases are known to have important roles in apoptosis of irradiated hair cells. 7 , 8 , 9 , 10 N -acetylcysteine, 11 epicatechin 10 and metformin 12 have been previously demonstrated to be effective in reducing apoptosis in irradiated hair cells. Because studies have been limited, the mechanisms underlying IR-induced auditory cell death remain unclear and require further investigation.…”

mentioning

confidence: 99%

MicroRNA-207 enhances radiation-induced apoptosis by directly targeting akt3 in cochlea hair cells

Ren

et al. 2014

Cell Death Dis

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MicroRNAs (miRNAs) have important roles in various types of cellular biological processes. Our study aimed to determine whether miRNAs function in the regulation of ionizing radiation (IR)-induced cell death in auditory cells and to determine how they affect the cellular response to IR. Microarray and qRT-PCR were performed to identify and confirm the differential expression of miRNAs in the cochlea hair cell line HEI-OC1 and in vivo after IR. Upregulation or downregulation of miRNAs using miRNA mimics or inhibitor were detected to characterize the biological effects of the indicated miRNAs. Bioinformatic analyses, luciferase reporter assays and mRNA knockdown were performed to identify a miRNA target gene. We determined that miR-207 was significantly upregulated after IR. MiR-207 enhances IR-induced apoptosis and DNA damage in HEI-OC1 cells. Furthermore, Akt3 was confirmed to be a direct target of miR-207. Downregulation of Akt3 mimics the effects of miR-207. MiR-207 enhances IR-induced apoptosis by directly targeting Akt3 and anti-miR-207 may have a potential role in protecting cochlea hair cells from IR.

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confidence: 99%

MicroRNA-207 enhances radiation-induced apoptosis by directly targeting akt3 in cochlea hair cells

Ren

et al. 2014

Cell Death Dis

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“…Metformin on its own was not found to be ototoxic. 88 Decades of clinical use have demonstrated that metformin is generally well-tolerated and safe even in prediabetics as a preventative agent. 48 Adverse effects, when they occur, are generally gastrointestinal in origin.…”

Section: Resultsmentioning

confidence: 99%

Novel Indications for Commonly Used Medications as Radiation Protectants in Spaceflight

McLaughlin¹,

Donoviel²,

Jones³

2017

aerosp med hum perform

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Background In the space environment, the traditional radioprotective principles of time, distance, and shielding become difficult to implement. Additionally, the complex radiation environment inherent in space, the chronic exposure timeframe, and the presence of numerous confounding variables complicate the process of creating appropriate risk models for astronaut exposure. Pharmaceutical options hold tremendous promise to attenuate acute and late effects of radiation exposure in the astronaut population. Pharmaceuticals currently approved for other indications may also offer radiation protection, modulation, or mitigation properties along with a well-established safety profile. Currently there are only three agents which have been clinically approved to be employed for radiation exposure, and these only for very narrow indications. This review identifies a number of agents currently approved by the U.S. Food and Drug Administration (FDA) which could warrant further investigation for use in astronauts. Specifically, we examine preclinical and clinical evidence for statins, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), metformin, calcium channel blockers, β adrenergic receptor blockers, fingolimod, N-acetylcysteine, and pentoxifylline as potential radiation countermeasures.

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“…Guinea pig in vivo model for fractionated radiation ototoxicity also demonstrated HL in the higher frequencies (22)(23)(24). Although the molecular mechanisms behind HL for fractionated radiation likely differ than for single-fraction radiation ototoxicity, both types of radiation exposure preferentially affect the basal turn of the cochlea, suggesting that the apical and middle turns are more resilient than the basal turn to radiation injury.…”

Section: Discussionmentioning

confidence: 98%

Dexamethasone Protects Against Radiation-induced Loss of Auditory Hair Cells In Vitro

Dinh

Chen

Padgett

et al. 2015

Otology &Amp; Neurotology

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Safety and Otoprotection of Metformin in Radiation‐Induced Sensorineural Hearing Loss in the Guinea Pig

Abstract: Metformin is not ototoxic or radioprotective in vitro or in vivo. Ears solely subjected to metformin had better hearing thresholds than the rest of the groups.

Cited by 20 publications

References 32 publications

MicroRNA-207 enhances radiation-induced apoptosis by directly targeting akt3 in cochlea hair cells

MicroRNA-207 enhances radiation-induced apoptosis by directly targeting akt3 in cochlea hair cells

Novel Indications for Commonly Used Medications as Radiation Protectants in Spaceflight

Dexamethasone Protects Against Radiation-induced Loss of Auditory Hair Cells In Vitro

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