Potentiation of Ototoxicity by Glutathione Depletion

Hoffman, Denise; Jones-King, Kitty L.; Whitworth, Craig; Rybak, Leonard P.

doi:10.1177/000348948809700107

Cited by 96 publications

(37 citation statements)

References 18 publications

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“…Oxidative stress has been implicated in the ototoxicity of several agents that potentiate NIHL, including aminoglycoside antibiotics (e.g., Garetz et al 1994;Hester et al 1998;Hoffman et al 1987Hoffman et al , 1988, the antineoplastic agent cisplatin Rybak et al 1995;Campbell et al 1996Campbell et al , 1999Gabaizadeh et al 1997), and carbon monoxide (Rao and Fechter 2000). Oxidative stress is also suspected to result from hydrogen cyanide treatment which also promotes NIHL (Fechter et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Fechter

Gearhart

Shirwany

2004

JARO - Journal of the Association for Research in Otolaryngolog

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Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl-N-tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile.

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Section: Discussionmentioning

confidence: 99%

Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Fechter

Gearhart

Shirwany

2004

JARO - Journal of the Association for Research in Otolaryngolog

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“…Subsequently, the metabolism of Ag to toxic compounds inactivated by glutathione in the ears and kidneys was proposed (10). Recently, two reports have demonstrated that a toxic metabolite had to be generated before Ag cytotoxicity to guinea pig cochlear hair cells could be obtained in vitro (5,11).…”

Section: Discussionmentioning

confidence: 99%

Effects of polyaspartic acid on pharmacokinetics of tobramycin in two strains of rat

Reinhard

Bekersky

Sanders

et al. 1994

Antimicrob Agents Chemother

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To provide insight into polyaspartic acid nephroprotection and differences in aminoglycoside renal toxicity between two rat strains, the single-dose pharmacokinetics of tobramycin was examined in the presence and absence of polyaspartic acid. Following a single subcutaneous 6.5-mg/kg dose of tobramycin alone, higher aminoglycoside concentrations were measured in Sprague-Dawley rats than in Fischer rats (P < 0.05). Simultaneous administration of polyaspartic acid (50 mg/kg) and tobramycin did not alter the concentrations of tobramycin in serum. The amount of tobramycin in renal tissue and the amount recovered in urine over a 24-h period were greater in both rat strains when tobramycin and polyaspartic acid were given concomitantly. Rats from each strain were randomly assigned to treatment groups in either part 1 or 2 of the experiment. Part 1 addressed serum pharmacokinetics and consisted of 24 rats of each strain that received a single 6.5-mg/kg subcutaneous dose of tobramycin dissolved in sterile water for injection (sterile tobramycin sulfate; kindly donated by Eli Lilly & Co., Indianapolis, Ind.). A low dose of tobramycin was selected to avoid any complicating effect of Ag-induced renal dysfunction on the pharmacokinetics. An additional 24 rats of each strain received the same dose of tobramycin plus 50 mg of PAA (poly-L-aspartic acid, Na salt; molecular weight, 9,600-13,000; Sigma Chemical Co., St. Louis, Mo.) per kg dissolved in sterile water for injection. The PAA was injected subcutaneously at a site distant from the tobramycin immediately after the tobramycin injection. Serum was collected from three rats of each strain and each treatment group at 0, 15, 30, 45, 60, 120, 180, and 240

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“…Incomplete protection may be related to observations that many hydroxyl scavengers are only partially effective in inhibiting lipid peroxidation as they compete for OH in 'free solution' but do not cross the lipid membrane barriers to scavenge OH within the cells (for additional detail, see Halliwell and Gutteridge, 1998). Manipulation of endogenous GSH with the above agents also affects cisplatin-induced injury (Campbell et al, 1996;1999;Hu et al, 1999;Rybak et al, 2000;, and aminoglycoside ototoxicity (Hoffman et al, 1988;Garetz et al, 1994a;1994b;Lautermann and Schacht, 1996). Subsequent corroboration of the importance of endogenous antioxidants has come from genetically manipulated mice in which endogenous antioxidant protection was reduced via deletion of copper-zinc super oxide dismutase (Sod1) (Ohlemiller et al, 1999a;McFadden et al, 2001) or glutathione peroxidase (Gpx1) (Ohlemiller et al, 2000).…”

Section: Endogenous Antioxidant Defense Against Nihlmentioning

confidence: 99%

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

et al. 2007

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Recent research has shown the essential role of reduced blood flow and free radical formation in the cochlea in noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant late formation 7-10 days following noise exposure, and one mechanism underlying noise-induced reduction in cochlear blood flow has finally been identified. These new insights have led to the formulation of new hypotheses regarding the molecular mechanisms of NIHL; and, from these, we have identified interventions that prevent NIHL, even with treatment onset delayed up to 3 days post-noise. It is essential to now assess the additive effects of agents intervening at different points in the cell death pathway to optimize treatment efficacy. Finding safe and effective interventions that attenuate NIHL will provide a compelling scientific rationale to justify human trials to eliminate this single major cause of acquired hearing loss.

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Potentiation of Ototoxicity by Glutathione Depletion

Cited by 96 publications

References 18 publications

Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Effects of polyaspartic acid on pharmacokinetics of tobramycin in two strains of rat

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

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