Potential diagnostic biomarkers for early detection of idiopathic sensorineural hearing loss in type 2 diabetes mellitus patients

Santosa, Agus; Suastika, I Ketut; Saraswasti, Made Ratna; Suardana, Wayan; Sujaya, I Nengah

doi:10.15562/ijbs.v16i1.371

Cited by 3 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…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 hearing loss (14), lead toxicity (15), presbycusis (16), sudden SNHL (17), and Ménière'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

Otol Neurotol

View full text Add to dashboard Cite

Hypothesis Ototoxin cyclodextrin (CDX) will induce a burst in serum prestin when quantified with automated Western blot analysis. Background 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. Previously, we demonstrated a burst in serum prestin after cisplatin exposure using enzyme-linked immunosorbent assayELISA. Methods Guinea pigs were treated with either 3,000 or 4,000 mg/kg CDX, and serum samples were obtained through 3 days after exposure. Serum prestin levels were quantified using automated blot analysis, western and hair cell counts were obtained. Results Both 3,000 and 4,000 mg/kg resulted in robust OHC loss, although more variability was seen at the lower dose. Automated Western blot analysis demonstrated that the prestin profile after CDX exposure is different than baseline. Specifically, a new ~134- kDa band accounted for the prestin burst after ototoxin ablation of OHCs at both doses. Conclusions We reproduced the prestin burst seen after cisplatin administration using CDX. Automated Western blot western analysis revealed that a ~a ~ 134- kDa species of prestin is responsible for the burst. We suggest that the induced band may be a prestin dimer, which could serve as a biomarker for early detection of ototoxicity in the clinical setting. These results add further promise to the potential of serum prestin to serve as an ototoxicity biomarker when using therapeutics with ototoxic properties.

show abstract

Verification of Outer Hair Cell Motor Protein, Prestin, as a Serological Biomarker for Mouse Cochlear Damage

Zheng,

Zhou,

Fuentes

et al. 2024

IJMS

View full text Add to dashboard Cite

The motor protein prestin, found in the inner ear’s outer hair cells (OHCs), is responsible for high sensitivity and sharp frequency selectivity in mammalian hearing. Some studies have suggested that prestin could be a serological biomarker for cochlear damage, as OHCs are highly vulnerable to damage from various sources. However, the reported data are inconsistent and lack appropriate negative controls. To investigate whether prestin can be used as a serological biomarker for cochlear damage or stress, we measured prestin quantities in the bloodstreams of mice using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that rapidly kill OHCs. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect prestin specifically. The ELISA kit that could detect the prestin protein from cochlear homogenates failed to detect prestin in the bloodstream, despite there being significant damage to OHCs in the cochleae. Furthermore, the optical densities of the serum samples, which correlate to prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice using ELISA.

show abstract

Potential diagnostic biomarkers for early detection of idiopathic sensorineural hearing loss in type 2 diabetes mellitus patients

Cited by 3 publications

References 18 publications

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

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

Automated Western Blot Analysis of Ototoxin-Induced Prestin Burst in the Blood after Cyclodextrin Exposure

Verification of Outer Hair Cell Motor Protein, Prestin, as a Serological Biomarker for Mouse Cochlear Damage

Contact Info

Product

Resources

About