Evaluation of Apoptotic Markers in HEI-OC1 Cells Treated with Gentamicin with and without the Mitochondria-Targeted Antioxidant Mitoquinone

Jadidian, Armon; Antonelli, Patrick J.; Ojano-Dirain, Carolyn P.

doi:10.1097/mao.0000000000000517

Cited by 11 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Triphenylphosphonium has been shown to inhibit oxidative phosphorylation in vitro (36). Similarly, we found that dTPP decreased HEI-OC1 cell survival (21) and upregulated Bak gene expression (37). However, the concentrations used in vitro are typically 10 to 100 times greater than those from oral dosing; thus, the unspecific effect of dTPP is unlikely to occur with oral dosing in animal or human subjects where effective drug clearance occurs (36).…”

Section: Discussionmentioning

confidence: 86%

Mitochondria-Targeted Antioxidant MitoQ Reduces Gentamicin-Induced Ototoxicity

Ojano-Dirain¹,

Antonelli²,

Prell³

2014

Otology &Amp; Neurotology

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 86%

Mitochondria-Targeted Antioxidant MitoQ Reduces Gentamicin-Induced Ototoxicity

Ojano-Dirain¹,

Antonelli²,

Prell³

2014

Otology &Amp; Neurotology

Self Cite

View full text Add to dashboard Cite

show abstract

“…A robust protective effect was observed at 500 nM concentration, and was present at D1-D3. c-Abl has been shown to be up-regulated in mouse oC following gentamicin exposure [ 34 ]. c-Src signaling has been implicated in noise-induced hearing loss, and treatment of chinchillas with Src inhibitors on the round window membrane prior to noise exposure was found to protect against HC death as measured by threshold shift and cyctocochleogram.…”

Section: Discussionmentioning

confidence: 99%

A kinase inhibitor library screen identifies novel enzymes involved in ototoxic damage to the murine organ of Corti

et al. 2017

View full text Add to dashboard Cite

Ototoxicity is a significant side effect of a number of drugs, including the aminoglycoside antibiotics and platinum-based chemotherapeutic agents that are used to treat life-threatening illnesses. Although much progress has been made, the mechanisms that lead to ototoxic loss of inner ear sensory hair cells (HCs) remains incompletely understood. Given the critical role of protein phosphorylation in intracellular processes, including both damage and survival signaling, we screened a library of kinase inhibitors targeting members of all the major families in the kinome. Micro-explants from the organ of Corti of mice in which only the sensory cells express GFP were exposed to 200 μM of the ototoxic aminoglycoside gentamicin with or without three dosages of each kinase inhibitor. The loss of sensory cells was compared to that seen with gentamicin alone, or without treatment. Of the 160 inhibitors, 15 exhibited a statistically significant protective effect, while 3 significantly enhanced HC loss. The results confirm some previous studies of kinase involvement in HC damage and survival, and also highlight several novel potential kinase pathway contributions to ototoxicity.

show abstract

“…There is evidence that suggests there is a link between antibiotic‐associated tissue damage and mitochondrial function. Aminoglycoside‐mediated ototoxicity is associated with mutations in mitochondrial DNA and changes in mitochondrial respiration, which could lead to ROS formation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Bactericidal antibiotics promote oxidative damage and programmed cell death in sinonasal epithelial cells

Kohanski

Tharakan

London

et al. 2017

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

Background Antibiotics are widely and heavily used in the treatment of chronic sinusitis. Bactericidal antibiotics can stimulate reactive oxygen species (ROS) formation, a pro-inflammatory response and cell death in cultured human sinonasal epithelial cells(SNECs). Sulforaphane is a potent stimulator of the antioxidant Nrf-2 system and a suppressor of inflammation. In this study we utilized sulforaphane to further explore the relationship between levofloxacin treatment, ROS formation and the cell death response. Methods SNECs were collected from patients during endoscopic sinus surgery and grown in culture at the air-liquid interface. Differentiated SNECs were stimulated with levofloxacin with or without sulforaphane pretreatment. Reactive oxygen species were quantified. Apoptosis markers of Caspase-3 activity and DNA fragmentation were quantified. Results Cultured SNECs treated with levofloxacin resulted in a significant increase in activity of the pro-apoptotic Caspase-3 protease (5.9 fold, p = 0.01). The increase in activity was suppressed by pretreatment with sulforaphane (1.9 fold). ROS levels increased with levofloxacin treatment, (range 1.2-1.8 fold) but were not significantly suppressed by pretreatment with sulforaphane (range 1-1.3 fold). Discussion In this study, we demonstrate that treatment of cultured SNECs with levofloxacin leads to an increase in Caspase-3 activity. Sulforaphane pretreatment suppresses the increased apoptotic response possibly through its antioxidant stimulating properties. Our results suggest that levofloxacin treatment stimulates a potent pro-apoptotic possibly through an ROS-dependent mechanism. Future studies will explore if this antibiotic-induced response is harmful to recovery of function in those with sinusitis.

show abstract

Evaluation of Apoptotic Markers in HEI-OC1 Cells Treated with Gentamicin with and without the Mitochondria-Targeted Antioxidant Mitoquinone

Cited by 11 publications

References 29 publications

Mitochondria-Targeted Antioxidant MitoQ Reduces Gentamicin-Induced Ototoxicity

Mitochondria-Targeted Antioxidant MitoQ Reduces Gentamicin-Induced Ototoxicity

A kinase inhibitor library screen identifies novel enzymes involved in ototoxic damage to the murine organ of Corti

Bactericidal antibiotics promote oxidative damage and programmed cell death in sinonasal epithelial cells

Contact Info

Product

Resources

About