Glutathione Ester But Not Glutathione Protects Against Cisplatin-Induced Ototoxicity in a Rat Model

2003 ◽  
Vol 14 (03) ◽  
pp. 124-133 ◽  
Author(s):  
Kathleen C.M. Campbell ◽  
Deb L. Larsen ◽  
Robert P. Meech ◽  
Leonard P. Rybak ◽  
Larry F. Hughes
Keyword(s):  
Auditory Brainstem Response ◽  
Outer Hair Cell ◽  
Tone Burst ◽  
Auditory Brainstem ◽  
Control Group ◽  
Brainstem Response ◽  
Group A ◽  
Direct Administration ◽  
Response Thresholds ◽  
Para Determinar

Glutathione (GSH) provides an important antioxidant and detoxification pathway. We tested to determine if direct administration of GSH or GSH ester could reduce cisplatin- (CDDP) induced ototoxicity. We tested eight groups of five rats each: a control group, a group receiving 16 mg/kg ip CDDP infused over 30 minutes, and six groups receiving either GSH or GSH ester at 500, 1000, or 1500 mg/kg intraperitoneally 30 minutes prior to 16 mg/kg CDDP. Auditory brainstem response thresholds were measured for click and tone-burst stimuli at baseline and 3 days later. Outer hair cell (OHC) loss was measured for the apical, middle and basal turns. The 500 mg/kg GSH ester reduced hearing loss and OHC loss, but protection decreased as dosage increased, suggesting possible toxicity. GSH was not significantly protective. The best GSH ester protection was less than we have previously reported with D-methionine. El glutatión (GSH) brinda una importante vía antioxidante y de cetoxificación. Realizamos una prueba para determinar si la administración directa de GSH o del éster de GSH podía reducir la ototoxicidad inducida por cisplatino (CDDP). Hicimos una evaluación en ocho grupos de cinco ratas cada uno: un grupo control, un grupo que recibió CDDP intraperitoneal a 16 mg/kg en una ínfusión durante 30 minutos y seis grupos que recibieron intraperitonealmente GSH o el éster de GSH a 500, 1000 o 1500 mg/kg, 30 minutos antes del CDDP a 16 mg/kg. Se midieron umbrales de respuestas auditivas del tallo cerebral tanto para clicks como para bursts tonales, al inicio y 3 días después. La pérdida de células ciliadas externas (OHC) fue establecida a nivel de las vueltas apical, media y basal. La dosis de 500 mg/kg de éster de GSH redujo la hipoacusia y la pérdida de OHC, pero la protección disminuyó conforme la dosis se incrementó, sugiriendo una posible toxicidad. EL GSH no resultó significativamente protector. El mejor efecto protector del éster de GSH fue menor que el previamente reportado con D-Metionina.

Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs

2016 ◽  
Vol 156 (3) ◽  
pp. 543-548 ◽  
Author(s):  
Alan D. Tate ◽  
Patrick J. Antonelli ◽  
Kyle R. Hannabass ◽  
Carolyn O. Dirain
Keyword(s):  
Hearing Loss ◽  
Auditory Brainstem Response ◽  
Guinea Pigs ◽  
Outer Hair Cell ◽  
Auditory Brainstem ◽  
Response Threshold ◽  
Saline Control ◽  
Control Group ◽  
Cochlear Hair Cells ◽  
Brainstem Response

Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

Effects of noise exposure on neonatal auditory brainstem response thresholds in pregnant guinea pigs at different gestational periods

2016 ◽  
Vol 43 (1) ◽  
pp. 78-86
Author(s):  
Chihiro Morimoto ◽  
Kazuhiko Nario ◽  
Tadashi Nishimura ◽  
Ryota Shimokura ◽  
Hiroshi Hosoi ◽  
...  
Keyword(s):  
Auditory Brainstem Response ◽  
Guinea Pigs ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Brainstem Response ◽  
Response Thresholds

Analysis of Click and Swept-Tone Auditory Brainstem Response Results for Moderate and Severe Sensorineural Hearing Loss

2020 ◽  
Vol 25 (6) ◽  
pp. 336-344
Author(s):  
Jingqian Tan ◽  
Jia Luo ◽  
Xin Wang ◽  
Yanbing Jiang ◽  
Xiangli Zeng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Auditory Brainstem Response ◽  
Basilar Membrane ◽  
Auditory Brainstem ◽  
Sensorineural Hearing ◽  
Control Group ◽  
Hearing Sensitivity ◽  
Brainstem Response ◽  
Frequency Components

<b><i>Introduction:</i></b> Auditory brainstem response (ABR) is one of the commonly used methods in clinical settings to evaluate the hearing sensitivity and auditory function. The current ABR measurement usually adopts click sound as the stimuli. However, there may be partial ABR amplitude attenuation due to the delay characteristics of the cochlear traveling wave along the basilar membrane. To solve that problem, a swept-tone method was proposed, in which the show-up time of different frequency components was adjusted to compensate the delay characteristics of the cochlear basilar membrane; therefore, different ABR subcomponents of different frequencies were synchronized. <b><i>Methods:</i></b> The normal hearing group, moderate sensorineural hearing loss group, and severe sensorineural hearing loss group underwent click ABR and swept-tone ABR with different stimulus intensities. The latencies and amplitudes of waves I, III, and V in 2 detections were recorded. <b><i>Results:</i></b> It was found that the latency of each of the recorded I, III, and V waves detected by swept-tone ABR was shorter than that by click ABR in both the control group and experimental groups. In addition, the amplitude of each of the recorded I, III, and V waves, except V waves under 60 dB nHL in the moderate sensorineural hearing loss group, detected by swept-tone ABR was larger than that by click ABR. The results also showed that the swept-tone ABR could measure the visible V waves at lower stimulus levels in the severe sensorineural hearing loss group. <b><i>Conclusion:</i></b> Swept-tone improves the ABR waveforms and helps to obtain more accurate threshold to some extent. Therefore, the proposed swept-tone ABR may provide a new solution for better morphology of ABR waveform, which can help to make more accurate diagnosis about the hearing functionality in the clinic.

scholarly journals Otoprotective Effects of Zingerone on Cisplatin-Induced Ototoxicity

2020 ◽  
Vol 21 (10) ◽  
pp. 3503 ◽  
Author(s):  
Chang Ho Lee ◽  
Da-hye Lee ◽  
So Min Lee ◽  
So Young Kim
Keyword(s):  
Caspase 3 ◽  
Auditory Brainstem ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Auditory Thresholds ◽  
Expression Levels ◽  
Brainstem Response ◽  
Group A

Previous studies have described the effects of zingerone (ZO) on cisplatin (CXP)-induced injury to the kidneys, liver, and other organs but not to the cochlea. This study aimed to investigate the effects of ZO on CXP-induced ototoxicity. Eight-week-old Sprague–Dawley rats were used and divided into a control group, a CXP group, and a CXP + ZO group. Rats in the CXP group received 5 mg/kg/day CXP intraperitoneally for five days. Rats in the CXP + ZO group received 5 mg/kg/day CXP intraperitoneally for five days and 50 mg/kg/day ZO intraperitoneally for seven days. Auditory brainstem response thresholds (ABRTs) were measured before (day 0) and after (day 10) drug administration. Cochlear histology was examined using hematoxylin and eosin (H&E) staining and cochlear whole mounts. The expression levels of cytochrome P450 (CYP)1A1, CYP1B1, inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), and interleukin 6 (IL6) were estimated using quantitative reverse transcription-polymerase chain reaction. The expression levels of heme oxygenase 1 (HO1) and caspase 3 were analyzed via Western blotting. The auditory thresholds at 4, 8, and 16 kHz were attenuated in the CXP + ZO group compared with the CXP group. The mRNA expression levels of CYP1A1, CYP1B1, iNOS, NFκB, TNFα, and IL6 were lower in the CXP + ZO group than in the CXP group. The protein expression levels of HO1 and caspase 3 were lower in the CXP + ZO group than in the CXP group. Cotreatment with ZO exerted otoprotective effects against CXP-induced cochlear injury via antioxidative and anti-inflammatory activities involving CYPs, iNOS, NFκB, and TNFα.

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