Effect of cisplatin chemotherapy on the inner ear function and serum prestin concentration

Jalali, Mir Mohammad; Saedi, Hamid Saeidi; Saadat, Farshid

doi:10.1007/s00405-021-06967-3

Cited by 12 publications

(11 citation statements)

References 30 publications

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“…Therefore, monitoring of serum prestin level could potentially guide dosage and administration schedule of therapeutics with ototoxic properties. A recent report of elevated prestin levels in cisplatin-treated cancer patients with ototoxicity is consistent with this view [37]. It remains to be determined if prestin could be a helpful biomarker for assessing candidacy for novel pharmacotherapeutics aimed at hair cell regeneration.…”

Section: Discussionsupporting

confidence: 60%

Characterization of ototoxic-induced prestin burst in the blood and implications for developing prestin as an ototoxicity biomarker

Harrison

Driscoll

Farnsworth

et al. 2022

Preprint

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In the clinical realm, we primarily rely on audiological measures for diagnosis and surveillance of sensorineural hearing loss (SNHL) and have limited therapeutic options. We have proposed a blood-based biomarker approach to overcome this challenge by measuring the outer hair cell’s (OHC) electromotile protein, prestin, in the blood. In a guinea pig model of cyclodextran (CDX) ototoxicity, using western blots, we show that prestin in the blood may have several different forms and specifically the ~ 134 kDa form spikes after ototoxin ablation of OHCs. This form appears to be a glycosylated dimer likely secreted by the inner ear as exosomes reflecting increased expression after ototoxin exposure. These results suggest that the ~ 134 kDa dimer may serve as a biomarker for early detection of ototoxicity in the clinical setting. However, because prestin can still be measured in the blood after total ablation of OHCs, its ability to inform on OHC health is restricted to a narrow window after ototoxin-induced injury. Monitoring prestin, when using therapeutics with ototoxic properties, could guide dosage and administration schedule to minimize damage.

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Section: Discussionsupporting

confidence: 60%

Characterization of ototoxic-induced prestin burst in the blood and implications for developing prestin as an ototoxicity biomarker

Harrison

Driscoll

Farnsworth

et al. 2022

Preprint

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“…We were the rst to demonstrate that levels of circulating prestin rise rapidly after exposure to cisplatin in animal models [4,5]. Several other groups have since reported increased prestin levels in experimental models of ototoxicity using cisplatin [8,9] and amikacin [8] and in patients undergoing treatment with cisplatin [9,10]. Many have explored and reported promising results on the value of prestin as a biomarker in human SNHL [11][12][13], including noise-induced [14], lead toxicity [15], presbycusis [16], sudden SNHL [17] and Meniere's disease [18].…”

Section: Introductionmentioning

confidence: 99%

Automated western blot analysis of ototoxin-induced prestin burst in the blood after cyclodextrin exposure

Harrison

Driscoll

Farnsworth

et al. 2023

Preprint

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In the clinical realm, we primarily rely on audiological measures for diagnosis and surveillance of sensorineural hearing loss (SNHL) and have limited therapeutic options. We have proposed a blood-based biomarker approach to overcome this challenge by measuring the outer hair cell’s (OHC) electromotile protein, prestin, in the blood. In a guinea pig model of cyclodextrin (CDX) ototoxicity, using western blots, we show that prestin in the blood may have several different forms and specifically the ~ 134 kDa form spikes after ototoxin ablation of OHCs. This form appears to be a glycosylated dimer likely secreted by the inner ear as exosomes reflecting increased expression after ototoxin exposure. These results suggest that the ~ 134 kDa dimer may serve as a biomarker for early detection of ototoxicity in the clinical setting. However, because prestin can still be measured in the blood after total ablation of OHCs, its ability to inform on OHC health is restricted to a narrow window after ototoxin-induced injury. Monitoring prestin, when using therapeutics with ototoxic properties, could guide dosage and administration schedule to minimize damage.

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“…However, we (2,4) and others (3) have reported that prestin levels in the serum increase in advance of changes in auditory measures, thus making it a promising biomarker of ototoxicity. The early findings in human subjects further support such a role (3,7).…”

Section: Discussionmentioning

confidence: 56%

Serum Prestin After Ototoxin Exposure Is Not Dependent on Outer Hair Cell Loss

Harrison,

Driscoll,

Farnsworth

et al. 2024

Otol Neurotol

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Hypothesis Cyclodextrin (CDX)-induced serum prestin burst is not dependent on outer hair cell (OHC) loss. Background Serum prestin has been proposed as a biomarker for ototoxicity. We recently used an automated Western approach to quantify serum prestin changes in a newly introduced model of CDX ototoxicity. To gain insights into prestin as a biomarker, here we further characterize serum prestin in the CDX model. Methods Guinea pigs were treated with 750, 3,000, or 4,000 mg/kg CDX, and serum samples were obtained through up to 15 weeks after exposure. Serum prestin levels were quantified using automated Western, and hair cell counts were obtained. Results All three doses induced an N-glycosylated ~134-kDa prestin burst; however, only the 3,000 and 4,000 mg/kg resulted in robust OHC loss. Prestin levels returned to baseline where they remained up to 15 weeks in the absence of OHCs. Conclusion The ~134-kDa prestin burst induced after CDX administration is N-glycosylated, representing a posttranslational modification of prestin. Serum prestin seems to be a promising biomarker when using therapeutics with ototoxic properties because it is not dependent on OHC loss as a necessary event, thus affording the opportunity for early detection and intervention.

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Effect of cisplatin chemotherapy on the inner ear function and serum prestin concentration

Cited by 12 publications

References 30 publications

Characterization of ototoxic-induced prestin burst in the blood and implications for developing prestin as an ototoxicity biomarker

Characterization of ototoxic-induced prestin burst in the blood and implications for developing prestin as an ototoxicity biomarker

Automated western blot analysis of ototoxin-induced prestin burst in the blood after cyclodextrin exposure

Serum Prestin After Ototoxin Exposure Is Not Dependent on Outer Hair Cell Loss

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