Maria Raye Anne V Ng 1 , Patrick J Antonelli 1 , Jerin Joseph 1 , Carolyn Ojano Dirain 2 Show Affiliations »
Abstract
OBJECTIVE: To determine the effects of concurrent treatment with gentamicin and the mitochondria-targeted antioxidant mitoquinone (MitoQ; which may prevent gentamicin ototoxicity) on change in the mitochondrial membrane potential (Δψ(m)), a precursor of apoptosis. STUDY DESIGN: Prospective and controlled. SETTING: Academic research laboratory. SUBJECTS AND METHODS: LLC-PK1 (Lilly Laboratories Culture-Pig Kidney Type 1) and HEI-OC1 (House Ear Institute Organ of Corti 1) cells-renal and auditory cell lines, respectively-were used in this study. Δψ(m) was assessed by flow cytometry through the MitoProbe JC-1 Kit for Flow Cytometry in untreated LLC-PK1 and HEI-OC1 cells and cells exposed to low- (100µM) or high- (2000µM) dose gentamicin for 24 hours, with and without 0.5µM each of MitoQ or idebenone (IDB; an untargeted ubiquinone). RESULTS: Δψ(m) was not different in untreated LLC-PK1 cells and cells coincubated with low-dose gentamicin and MitoQ or IDB (P > .05). In HEI-OC1 cells, coincubation with low-dose gentamicin and MitoQ decreased Δψ(m) (P = .002). Coincubation of LLC-PK1 cells with high-dose gentamicin and DMSO, MitoQ, or IDB depolarized Δψ(m) (P < .0001), with MitoQ depolarizing the Δψ(m) to a greater extent than that of IDB (P = .03). In contrast, HEI-OC1 cells demonstrated a hyperpolarized Δψ(m) when coincubated with high-dose gentamicin and DMSO, MitoQ, or IDB (P < .001). CONCLUSION: The combination of gentamicin and MitoQ holds the potential to disrupt Δψ(m). This suggests a heightened need to monitor for toxicity in patients receiving both agents. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.
OBJECTIVE: To determine the effects of concurrent treatment with gentamicin and the mitochondria-targeted antioxidant mitoquinone (MitoQ ; which may prevent gentamicin ototoxicity ) on change in the mitochondrial membrane potential (Δψ(m)), a precursor of apoptosis. STUDY DESIGN: Prospective and controlled. SETTING: Academic research laboratory. SUBJECTS AND METHODS: LLC-PK1 (Lilly Laboratories Culture-Pig Kidney Type 1) and HEI-OC1 (House Ear Institute Organ of Corti 1) cells-renal and auditory cell lines, respectively-were used in this study. Δψ(m) was assessed by flow cytometry through the MitoProbe JC-1 Kit for Flow Cytometry in untreated LLC-PK1 and HEI-OC1 cells and cells exposed to low- (100µM) or high- (2000µM) dose gentamicin for 24 hours, with and without 0.5µM each of MitoQ or idebenone (IDB ; an untargeted ubiquinone ). RESULTS: Δψ(m) was not different in untreated LLC-PK1 cells and cells coincubated with low-dose gentamicin and MitoQ or IDB (P > .05). In HEI-OC1 cells, coincubation with low-dose gentamicin and MitoQ decreased Δψ(m) (P = .002). Coincubation of LLC-PK1 cells with high-dose gentamicin and DMSO , MitoQ , or IDB depolarized Δψ(m) (P < .0001), with MitoQ depolarizing the Δψ(m) to a greater extent than that of IDB (P = .03). In contrast, HEI-OC1 cells demonstrated a hyperpolarized Δψ(m) when coincubated with high-dose gentamicin and DMSO , MitoQ , or IDB (P < .001). CONCLUSION: The combination of gentamicin and MitoQ holds the potential to disrupt Δψ(m). This suggests a heightened need to monitor for toxicity in patients receiving both agents. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.
Entities: Chemical
Disease
Species
Keywords:
aminoglycoside; antioxidants; gentamicin; mitochondrial membrane potential; mitoquinone; ototoxicity
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Year: 2014
PMID： 25550222 DOI： 10.1177/0194599814564934
Source DB: PubMed Journal: Otolaryngol Head Neck Surg ISSN： 0194-5998 Impact factor: 3.497