Anion exchanger1 (AE1/SLC4A1) function is impaired in red blood cells from prediabetic subjects: Potential benefits of finger lime (Citrus australasica, Faustrime cultivar) juice extract.

Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia-induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress-related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/ß-spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition.

Distinct Sensory Hedonic Functions for Sourness in Adults.

Over the last half-century, variable responses to sweetness have repeatedly been shown to fall into a small number of hedonic responses, implying that looking only at group means may can obfuscate meaningfully different response patterns. Comparative data for sourness is quite sparse, especially in adults. While increased liking with higher acid concentration has been reported for some children, in adults, sourness is classically assumed to be aversive, with a monotonic drop in liking with increasing sourness. Here, we test this assumption using a simple model system or experimental beverage in convenience samples of adults from the United States (increasing citric acid in water) and Italy (increasing citric acid in pear juice). Participants rated intensity and liking of sampled stimuli. For both cohorts, we find clear evidence of three distinct patterns of responses: a strong negative group where liking dropped with increased sourness, an intermediate group who showed a more muted drop in liking with more sourness, and a strong positive group where liking increased with more sourness. Strikingly, both cohorts showed similar proportions of response patterns, with ~63-70% in the strong negative group, and 11-12% in the strong positive group, suggesting these proportions may be stable across cultures. Notably, the three groups did not differ by age or gender. These data support the existence of different hedonic response profiles to sour stimuli in adults, once again highlighting the importance of looking at individual differences and potential consumer segments, rather than merely averaging hedonic responses across all individuals within a group.

Interventions based on sensory-hedonic strategies and on nudging to facilitate vegetable and pulses consumption in the school environment.

Childhood and adolescence shape lifelong taste preferences and dietary habits, making them crucial periods for promoting healthy and sustainable eating. As students consume up to half of their daily energy intake at school, school interventions can have a significant impact on promoting plant-based diets. Although the benefits of promoting plant-based diets on children's and adolescents' health and environmental sustainability are well established and various studies report promising effects of interventions based on sensory-hedonic strategies and on nudging in promoting vegetables and pulses in schools, a comprehensive collection of those reports is lacking. Therefore, this systematic review aims to collect published literature on the above interventions in schools that focus on promoting the consumption of vegetables and pulses to children and adolescents. Three databases-PubMed, Scopus, and Web of Science-were searched over all years until March 2022 using pre-specified terms. From the 10.488 studies identified, a total of 57 studies reporting sensory-hedonic (e.g., manipulating food sensory properties or their hedonic value) or nudging (e.g., changing the presentation) interventions targeting children and/or adolescents in schools and aiming at promoting vegetables and/or pulses were included. Overall, interventions based on sensory-hedonic strategies (either enhancing the perception of well-accepted flavor and texture or manipulating their hedonic value) and on nudging (through incentives and prompts) are effective in promoting vegetables and pulses. A gap in the literature was identified for interventions targeting adolescents and promoting pulses. Finally, multicomponent interventions, rather than using one strategy alone, could be more successful.

Bringing down barriers to children's healthy eating: a critical review of opportunities, within a complex food system.

This narrative review revises the scientific evidence of recent years on healthy eating in children and adolescents, making sense of promising avenues of action, from a food system perspective. A conceptual framework is provided to better understand how eating habits of children and adolescents are shaped to identify key multisectoral approaches that should be implemented to promote healthier diets. The following influencing factors are discussed: individual factors (physiological and psychological factors, food preferences and food literacy competencies), factors within the personal and socio-cultural food environments, external food environments, and the supply chain. In each section, the main barriers to healthy eating are briefly discussed focussing on how to overcome them. Finally, a discussion with recommendations of actions is provided, anchored in scientific knowledge, and transferable to the general public, industry, and policymakers. We highlight that multidisciplinary approaches are not enough, a systems approach, with a truly holistic view, is needed. Apart from introducing systemic changes, a variety of interventions can be implemented at different levels to foster healthier diets in children through fostering healthier and more sustainable food environments, facilitating pleasurable sensory experiences, increasing their food literacy, and enhancing their agency by empowering them to make better food related decisions. Acknowledging children as unique individuals is required, through interpersonal interactions, as well as their role in their environments. Actions should aim to enable children and adolescents as active participants within sustainable food systems, to support healthier dietary behaviours that can be sustained throughout life, impacting health at a societal level.

Oxidative Stress and Immune Response in Melanoma: Ion Channels as Targets of Therapy.

Oxidative stress and immune response play an important role in the development of several cancers, including melanoma. Ion channels are aberrantly expressed in tumour cells and regulate neoplastic transformation, malignant progression, and resistance to therapy. Ion channels are localized in the plasma membrane or other cellular membranes and are targets of oxidative stress, which is particularly elevated in melanoma. At the same time, ion channels are crucial for normal and cancer cell physiology and are subject to multiple layers of regulation, and therefore represent promising targets for therapeutic intervention. In this review, we analyzed the effects of oxidative stress on ion channels on a molecular and cellular level and in the context of melanoma progression and immune evasion. The possible role of ion channels as targets of alternative therapeutic strategies in melanoma was discussed.

d-Galactose induced early aging in human erythrocytes: Role of band 3 protein.

Aging, a time-dependent multifaceted process, affects both cell structure and function and involves oxidative stress as well as glycation. The present investigation focuses on the role of the band 3 protein (B3p), an anion exchanger essential to red cells homeostasis, in a d-galactose ( d-Gal)-induced aging model. Anion exchange capability, measured by the rate constant of SO4²- uptake through B3p, levels of lipid peroxidation, oxidation of membrane sulfhydryl groups, B3p expression, methemoglobin, glycated hemoglobin (Hb), and the reduced glutathione/oxidized glutathione ratio were determined after exposure of human erythrocytes to 25, 35, 50, and 100 mmol/L d-Gal for 24 h. Our results show that: (i) in vitro application of d-Gal is useful to model early aging in human erythrocytes; (ii) assessment of B3p ion transport function is a sensitive tool to monitor aging development; (iii) d-Gal leads to Hb glycation and produces substantial changes on the endogenous antioxidant system; (iv) the impact of aging on B3p function proceeds through steps, first involving Hb glycation and then oxidative events at the membrane level. These findings offer a useful tool to understand the mechanisms of aging in human erythrocytes and propose B3p as a possible target for new therapeutic strategies to counteract age-related disturbances.

Oxidation Stress as a Mechanism of Aging in Human Erythrocytes: Protective Effect of Quercetin.

Aging is a multi-factorial process developing through a complex net of interactions between biological and cellular mechanisms and it involves oxidative stress (OS) as well as protein glycation. The aim of the present work was to verify the protective role of Quercetin (Q), a polyphenolic flavonoid compound, in a d-Galactose (d-Gal)-induced model of aging in human erythrocytes. The anion-exchange capability through the Band 3 protein (B3p) measured by the rate constant of the SO42- uptake, thiobarbituric acid reactive substances (TBARS) levels-a marker of lipid peroxidation-total sulfhydryl (-SH) groups, glycated hemoglobin (A1c), and a reduced glutathione/oxidized glutathione (GSH-GSSG) ratio were determined following the exposure of erythrocytes to 100 mM d-Gal for 24 h, with or without pre-incubation with 10 µM Q. The results confirmed that d-Gal activated OS pathways in human erythrocytes, affecting both membrane lipids and proteins, as denoted by increased TBARS levels and decreased total sulfhydryl groups, respectively. In addition, d-Gal led to an acceleration of the rate constant of the SO42- uptake through the B3p. Both the alteration of the B3p function and oxidative damage have been improved by pre-treatment with Q, which preferentially ameliorated lipid peroxidation rather than protein oxidation. Moreover, Q prevented glycated A1c formation, while no protective effect on the endogenous antioxidant system (GSH-GSSG) was observed. These findings suggest that the B3p could be a novel potential target of antioxidant treatments to counteract aging-related disturbances. Further studies are needed to confirm the possible role of Q in pharmacological strategies against aging.

Antioxidant Activity of Quercetin in a H2O2-Induced Oxidative Stress Model in Red Blood Cells: Functional Role of Band 3 Protein.

During their lifespan, red blood cells (RBCs) are exposed to a large number of stressors and are therefore considered as a suitable model to investigate cell response to oxidative stress (OS). This study was conducted to evaluate the potential beneficial effects of the natural antioxidant quercetin (Q) on an OS model represented by human RBCs treated with H2O2. Markers of OS, including % hemolysis, reactive oxygen species (ROS) production, thiobarbituric acid reactive substances (TBARS) levels, oxidation of protein sulfhydryl groups, CD47 and B3p expression, methemoglobin formation (% MetHb), as well as the anion exchange capability through Band 3 protein (B3p) have been analyzed in RBCs treated for 1 h with 20 mM H2O2 with or without pre-treatment for 1 h with 10 µM Q, or in RBCs pre-treated with 20 mM H2O2 and then exposed to 10 µM Q. The results show that pre-treatment with Q is more effective than post-treatment to counteract OS in RBCs. In particular, pre-exposure to Q avoided morphological alterations (formation of acanthocytes), prevented H2O2-induced OS damage, and restored the abnormal distribution of B3p and CD47 expression. Moreover, H2O2 exposure was associated with a decreased rate constant of SO42- uptake via B3p, as well as an increased MetHb formation. Both alterations have been attenuated by pre-treatment with 10 µM Q. These results contribute (1) to elucidate OS-related events in human RBCs, (2) propose Q as natural antioxidant to counteract OS-related alterations, and (3) identify B3p as a possible target for the treatment and prevention of OS-related disease conditions or aging-related complications impacting on RBCs physiology.

Remote testing: Sensory test during Covid-19 pandemic and beyond.

Restrictions adopted by many countries in 2020 due to Covid-19 pandemic had severe consequences on the management of sensory and consumer testing that strengthened the tendency to move data collection out of the laboratory. Remote sensory testing, organized at the assessor's home or workplace and carried out under the live online supervision of the panel leader, represents a trade-off between adequate control and the convenience of conducting testing out of the lab. The Italian Sensory Science Society developed the "Remote sensory testing" research project aimed at testing the effectiveness and validity of the sensory tests conducted remotely through a comparison with evaluations in a classical laboratory setting. Guidelines were developed to assist panel leaders in setting up and controlling the evaluation sessions in remote testing conditions. Different methods were considered: triangle and tetrad tests, Descriptive Analysis and Temporal Dominance of Sensations tests, all of which involved trained panels, and Check-All-That-Apply and hedonic tests with consumers. Remote sensory testing provided similar results to the lab testing in all the cases, with the exception of the tetrad test run at work. Findings suggest that remote sensory testing, if conducted in strict compliance with specifically developed sensory protocols, is a promising alternative to laboratory tests that can be applied with both trained assessors and consumers even beyond the global pandemic.

Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

ALTERTASTE: improving food pleasure and intake of oncology patients receiving chemotherapy.

ALTERTASTE is a prospective study to evaluate changes in taste/flavor perception and food preferences in patients treated with adjuvant or neoadjuvant chemotherapy for breast or colorectal cancer. The study adopts a longitudinal approach. Taste and odor responsiveness, food preferences and habits, emotions elicited by foods, and quality of life will be measured at six-time points: before chemotherapy (T0), after two cycles (T1, after around 1 month), after four cycles (T2, after around 2 months), after six cycles (T3, after around 4 months), at the end of chemotherapy (T4, after around 6 months) and 3 months after the conclusion of the therapy (T5). In addition, patients will be characterized for oral responsiveness and their psychological traits and attitudes toward food. The ALTERTASTE trial is expected to improve the understanding of the impact of chemotherapy on taste and smell and the repercussions of these alterations on food behaviors. Furthermore, the trial aims to develop an easy and reliable procedure to test smell, taste and food behavior alterations to allow a routine measure with patients. Clinical trial registration: NCT04495387 (ClinicalTrials.gov).

Lay abstract Malnutrition (under- or over-nutrition) is highly prevalent in cancer patients receiving chemotherapy and is an important predictor of morbidity, mortality, treatment response and toxicity. Alterations in taste and smell are frequently reported as side effects of chemotherapy and may contribute strongly to malnutrition through an impact on eating behaviors and to a worse quality of life. ALTERTASTE is a prospective longitudinal study to evaluate changes in taste/flavor perception and food preferences in patients treated with chemotherapy for breast, colon or rectal cancer. Taste and odor responsiveness, food preferences and habits, emotions elicited by foods, and quality of life will be measured at six-time points: before chemotherapy (T0), after two cycles (T1, after around 1 month), after four cycles (T2, after around 2 months), after six cycles (T3, after around 4 months), at the end of chemotherapy (T4, after around 6 months) and 3 months after the conclusion of the therapy (T5). In addition, patients will be characterized for oral responsiveness and psychological traits and attitudes toward food. The ALTERTASTE trial is expected to improve the understanding of the impact of chemotherapy on taste and smell and the repercussions of these alterations on food behaviors.

Healthier eating: Covid-19 disruption as a catalyst for positive change.

Healthy and sustainable diets are necessary for global development goals, but people struggle to modify their eating behaviours which are often habitual and resistant to change. However, disruption can provide the impetus for change, and in the present research we view the Covid-19 pandemic as a potential catalytic disruption with the potential to induce positive behaviour change. Data were obtained from ~900 USA adults, of which 44% self-reported to have made positive dietary change/s. Those who did so tended to be younger rather than older and with higher educational attainment. They also were less food neophobic than people who did not make positive change/s and placed greater importance on health as a motive of daily decisions about what to eat and drink. The contribution of psychographic variables in differentiating between groups of people who did / did not make positive changes once again show their importance in uncovering and explaining the complex factors that motivate food-related consumer behaviour. It seems this holds also when daily lives are disrupted by unforeseen events.

Relationship between odor intensity estimates and COVID-19 prevalence prediction in a Swedish population.

In response to the COVID-19 pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a step-wise manner, monitoring of COVID-19 prevalence is of importance to guide decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure. Online measures of how intense common household odors are perceived and symptoms of COVID-19 were collected from 2440 Swedes. Average odor intensity ratings were then compared to predicted COVID-19 population prevalence over time in the Swedish population and were found to closely track each other (r=-0.83). Moreover, we found that there was a large difference in rated intensity between individuals with and without COVID-19 symptoms and number of symptoms was related to odor intensity ratings. Finally, we found that individuals progressing from reporting no symptoms to subsequently reporting COVID-19 symptoms demonstrated a large drop in olfactory performance. These data suggest that measures of odor intensity, if obtained in a large and representative sample, can be used as an indicator of COVID-19 disease in the general population. Importantly, this simple measure could easily be implemented in countries without widespread access to COVID-19 testing or implemented as a fast early response before wide-spread testing can be facilitated.

Emerging techniques applied to by-products for food fortification.

Considering the increasing consumer demand for healthy food, the extract from broccoli by-products was studied. To this aim, in the first step, three extraction techniques were compared in terms of extraction efficiency. The best method was the pressurized liquid extraction. Then, the extract microencapsulation was optimized in terms of type of wall material (between Capsul and maltodextrins), concentration of wall material (10-20-30%, w/v), core/wall material ratio (1:2, 1:5, 1:10, 1:20) and inlet temperature (80, 100, 130, 150, 170 °C). The optimal conditions were found with 10% maltodextrins as wall material, core/wall material ratio 1/2 at 80 °C. Finally, the obtained microencapsulated extract was added at 5% (w/w) to fish burgers. Results demonstrated that total phenolic content, total flavonoids and antioxidant activity of enriched fish products were significantly higher than the control burgers, thus confirming that both process and cooking did not greatly affect the nutritional properties of extracted compounds.

Individual Variation in PROP Status, Fungiform Papillae Density, and Responsiveness to Taste Stimuli in a Large Population Sample.

Despite considerable research investigating the role of 6-n-propylthiouracil bitterness perception and variation of fungiform papillae density in food perception, this relationship remains controversial as well as the association between the 2 phenotypes. Data from 1119 subjects (38.6% male; 18-60 years) enrolled in the Italian Taste project were analyzed. Responsiveness to the bitterness of 6-n-propylthiouracil was assessed on the general Labeled Magnitude Scale. Fungiform papillae density was determined from manual counting on digital images of the tongue. Solutions of tastes, astringent, and pungent sensations were prepared to be moderate/strong on a general Labeled Magnitude Scale. Four foods had tastants added to produce 4 variations in target sensations from weak to strong (pear juice: citric acid, sourness; chocolate pudding: sucrose, sweetness; bean purée: sodium chloride, saltiness; and tomato juice: capsaicin, pungency). Women gave ratings to 6-n-propylthiouracil and showed fungiform papillae density that was significantly higher than men. Both phenotype markers significantly decreased with age. No significant correlations were found between 6-n-propylthiouracil ratings and fungiform papillae density. Fungiform papillae density variation does not affect perceived intensity of solutions. Responsiveness to 6-n-propylthiouracil positively correlated to perceived intensity of most stimuli in solution. A significant effect of fungiform papillae density on perceived intensity of target sensation in foods was found in a few cases. Responsiveness to 6-n-propylthiouracil positively affected all taste intensities in subjects with low fungiform papillae density whereas there were no significant effects of 6-n-propylthiouracil in those with high fungiform papillae density. These data highlight a complex interplay between 6-n-propylthiouracil status and fungiform papillae density and the need of a critical reconsideration of their role in food perception and acceptability.

Bioactive compounds from orange epicarp to enrich fish burgers.

BACKGROUND: The orange industry produces considerable amounts of by-products, traditionally used for animal feed or fuel production. Most of these by-products could be used as functional ingredients. To assess the potential food application of orange epicarp, different percentages of micro-encapsulated orange extract were added to fresh fish burgers. Then, an in vitro digestion was also carried out, before and after micro-encapsulation, to measure the bio-accessibility of the active compounds. RESULTS: A significant increase of bio-accessibility of bioactive compounds has been observed in the orange epicarp extract after micro-encapsulation by spray-drying. From the sensory point of view, the fish sample enriched with 50 g kg-1 micro-encapsulated extract was the most comparable to the control burger, even if it showed a higher phenolic, flavonoid and carotenoid bio-accessibility. CONCLUSION: Orange epicarp may be used as a food additive to enhance the health content of food products. The micro-encapsulation is a valid technique to protect the bioactive compounds and increase their bio-accessibility. © 2017 Society of Chemical Industry.

Optimization and characterization of gluten-free spaghetti enriched with chickpea flour.

This work was focused on the optimization and characterization of maize-based spaghetti fortified with chickpea flour. To the aim, the study has been organized in two subsequent trials. In the first one, the chickpea flour amount added to the spaghetti was continuously increased until the overall sensory quality of pasta reached its sensory threshold. Spaghetti samples loaded with 15% chickpea flour showed poor elasticity and increased firmness, so this concentration represented the highest chickpea flour concentration to be used. The second experimental step was aimed to improve the overall sensory quality of the enriched spaghetti by means of hydrocolloids as pectin, guar flour and agar. Final pasta was characterized for the nutritional composition, the glycemic response and the main quality attributes. The best results were obtained by the addition of guar flour.

Effect of durum wheat cultivars on physico-chemical and sensory properties of spaghetti.

BACKGROUND: Mixtures of different cultivars provide semolina with proper processing properties but not always good nutritional properties. In this study, the effects of mono-varietal cultivars of durum wheat on pasta quality were evaluated in order to find a good balance between nutritional and sensory properties of the final product. RESULTS: Durum wheat spaghetti was manufactured using semolina from six mono-varietal cultivars. A commercially available semolina mixture was also used to produce a control pasta sample. Instrumental (i.e. rheological and texture analysis), sensory (i.e. elasticity, firmness, adhesiveness) and nutritional (i.e. protein, ash and fibre content, glycaemic index) analyses were carried out. Results highlighted differences between selected cultivars. In particular, spaghetti obtained with Anco Marzio and Cappelli semolina (modern and old cultivars, respectively) showed the highest protein content and the lowest cooking loss, compared with the other samples. CONCLUSION: Spaghetti made with Cappelli semolina showed the lowest adhesiveness and the highest hardness; it recorded the best overall quality and presented the lowest glycaemic response. Hence, durum wheat pasta with a good balance between nutritional and cooking quality could be obtained from semolina based on mono-varietal cultivars. © 2013 Society of Chemical Industry.

Arousal and the modulation of sensory experience: evidence from food-related emotions.

Across sensory systems, several stimulus collative characteristics, including intensity, novelty, complexity and perceived dangerousness, are known to elicit high levels of physiological and psychological arousal. It has become apparent that food rejections by both children and adults are frequently linked to such arousal-inducing characteristics. This paper examines how arousal and arousability are important elements in responding to stimuli generally, but specifically to foods, ultimately influencing food preferences and choices. It is clear that responses to sensory properties are subject not just to variations in perceptual sensitivity due to genetics or experience-as in the case of widely rejected qualities such as bitterness or pungency-but also to the arousal potential of those stimuli. Moreover, this is linked to various enduring aspects of personality, suggesting that the impact of arousal on food choices is merely one aspect of a more general sensory sensitivity. The impact of diet on various health outcomes underlines the importance of understanding the relationship of arousal to food choices. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Oxidative stress-related cellular aging causes dysfunction of the Kv3.1/KCNC1 channel reverted by melatonin.

The voltage-gated Kv3.1/KCNC1 channel is abundantly expressed in fast-spiking principal neurons and GABAergic inhibitory interneurons throughout the ascending auditory pathway and in various brain regions. Inactivating mutations in the KCNC1 gene lead to forms of epilepsy and a decline in the expression of the Kv3.1 channel is involved in age-related hearing loss. As oxidative stress plays a fundamental role in the pathogenesis of epilepsy and age-related hearing loss, we hypothesized that an oxidative insult might affect the function of this channel. To verify this hypothesis, the activity and expression of endogenous and ectopic Kv3.1 were measured in models of oxidative stress-related aging represented by cell lines exposed to 100 mM d-galactose. In these models, intracellular reactive oxygen species, thiobarbituric acid reactive substances, sulfhydryl groups of cellular proteins, and the activity of catalase and superoxide dismutase were dysregulated, while the current density of Kv3.1 was significantly reduced. Importantly, the antioxidant melatonin reverted all these effects. The reduction of function of Kv3.1 was not determined by direct oxidation of amino acid side chains of the protein channel or reduction of transcript or total protein levels but was linked to reduced trafficking to the cell surface associated with Src phosphorylation as well as metabolic and endoplasmic reticulum stress. The data presented here specify Kv3.1 as a novel target of oxidative stress and suggest that Kv3.1 dysfunction might contribute to age-related hearing loss and increased prevalence of epilepsy during aging. The pharmacological use of the antioxidant melatonin can be protective in this setting.