Manganese in toenails is associated with hearing loss at high frequencies in humans

<p><b>Purpose:</b> Elevated hearing thresholds from high frequencies are known to be one of the hallmarks of age-related hearing loss. Our recent study showed accumulation of manganese (Mn) in inner ears resulting in acceleration of age-related hearing loss in mice orally exposed to Mn. However, there is no evidence showing an association between Mn in non-invasive biological samples and hearing loss in humans evaluated by pure tone audiometry (PTA). In this study, we evaluated Mn in non-invasive biological samples as a possible biomarker for hearing loss in humans.</p> <p><b>Materials and methods:</b> We determined hearing levels by PTA and Mn levels in toenails, hair and urine with an inductively coupled plasma mass spectrometer (ICP-MS) in 145 healthy subjects in Bangladesh.</p> <p><b>Results:</b> Multivariable analyses showed that Mn levels in toenails, but not in hair and urine samples, were significantly associated with hearing loss at 8 kHz and 12 kHz. Moreover, our experimental study showed a significant correlation between Mn levels in inner ears and nails, but not hair, in mice orally exposed to Mn.</p> <p><b>Conclusions:</b> The results provide novel evidence that Mn in toenails is a possible biomarker for hearing loss at high frequencies in humans.</p

Arsenic level in toenails is associated with hearing loss in humans

<div><p>Arsenic (As) pollution in drinking water is a worldwide health risk for humans. We previously showed hearing loss in young people who live in areas of As-polluted drinking water and in young mice orally treated with As. In this study, we epidemiologically examined associations between As levels in toenails and hearing in 145 Bangladeshi aged 12–55 years in 2014. Levels of As in toenails, but not those in urine, were shown to be significantly correlated with hearing loss at 4 kHz [odds ratio (OR) = 4.27; 95% confidence interval (CI): 1.51, 12.05], 8 kHz (OR = 3.91; 95% CI: 1.47, 10.38) and 12 kHz (OR = 4.15; 95% CI: 1.55, 11.09) by multivariate analysis with adjustments for age, sex, smoking and BMI. Our experimental study further showed a significant association between As levels in inner ears and nails (r = 0.8113, p = 0.0014) in mice orally exposed to As, suggesting that As level in nails is a suitable index to assess As level in inner ears. Taken together, the results of our study suggest that As level in nails could be a convenient and non-invasive biomarker for As-mediated hearing loss in humans.</p></div

Characteristics of the study participants.

<p>Characteristics of the study participants.</p

Associations between hearing levels and confounding factors including age, BMI, sex and smoking.

<p>Associations between hearing levels and confounding factors including age, BMI, sex and smoking.</p

Correlation between As levels in inner ear and nails in mice.

<p>Correlation between As levels in inner ears and nails was determined by Spearman correlation coefficients.</p

Adjusted ORs (95% CI) for hearing loss and As levels in biological samples (n = 145)^a.

<p>Adjusted ORs (95% CI) for hearing loss and As levels in biological samples (n = 145)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198743#t004fn002" target="_blank">^a</a>.</p

As levels in biological samples from humans.

<p>As levels in biological samples from humans.</p

Association between hearing thresholds and As levels in biological samples in humans.

<p>(A) Hearing levels (mean ± SD) at 1, 4, 8 and 12 kHz in the high As group (≥ 0.60 μg/g; n = 97) and low As group (< 0.60 μg/g; n = 48) in toenails are presented. (B) Hearing levels (mean ± SD) at 1, 4, 8 and 12 kHz in the high As group (≥ 76.12 μg/L; n = 73) and low As group (< 76.12 μg/L; n = 72) in urine samples are presented. Significant differences (*p<0.05; **p < 0.01; ***p<0.001) were determined by the Mann-Whitney <i>U</i> test.</p