Eliane Dallegrave

Purpose: Ototoxicity caused by chemotherapy is a growing problem. Literature highlights the effects of platinum compounds. However, other chemotherapy drugs also have demonstrated audiological changes. The objective of this study was to compare pre- and post-treatment distortion product otoacoustic emissions (DPOAEs) in adult patients undergoing different chemotherapy regimens. Methods: Cohort study comprising 174 individuals receiving chemotherapy (CT) between April 2022 and December 2023. DPOAE were evaluated in all patients at 2 kHz, 4 kHz, 6 kHz, 8 kHz, 10 kHz, and 12 kHz, before initiating chemotherapy and after completing the treatment. For differential analysis, the protocols were grouped into CT with platinum-based agents and other protocols. Results: A reduction in response in at least one frequency of the DPOAE test was observed in 79% of the patients. 81% of those who received CT without platinum derivatives exhibited alterations in post-treatment examinations, whereas in the group with platinum-based compounds, alterations were observed in 79% of the subjects. Different percentages of response deterioration were observed across frequencies: 27.6% at 2 kHz, 24.6% at 4 kHz, 41.2% at 6 kHz, 58.8% at 8 kHz, 57.4% at 10 kHz, and 72.4% at 12 kHz. The ototoxic effect of chemotherapy protocols, with and without platinum, was more pronounced at higher frequencies, with no statistically significant difference between the groups. Conclusion: Chemotherapy has shown signs of ototoxicity through changes in DPOAEs in the sample studied. The ototoxic effects were similar between drug protocols with and without platinum, highlighting the need for audiological monitoring in all chemotherapy patients.

Cancer patients undergoing potentially-ototoxic chemotherapy may present a series of hearing disorders and risk factors prior to treatment. Thus, it is necessary to know the profile of these patients to promote preventive actions and guidelines regarding the hearing health of these individuals. To describe and relate the hearing characteristics of patients entering a chemotherapy service before the exposure to potentially-ototoxic drugs. We conducted a cross-sectional study of 261 individuals who started chemotherapy between April and December 2022. All patients filled out a hearing case history and underwent otoscopy. Individuals who had a non-altered otoscopy due to obstructive cerumen underwent distortion-product otoacoustic emissions (DPOAEs) at 2, 4, 6, 8, 10, and 12 kHz in both ears. In total, 83% of the patients reported good hearing and 31% described some level of hearing impairment. The most prevalent self-reported hearing issue was tinnitus (35%). Only 12% had a medical diagnosis of hearing loss, and 20% had obstructive cerumen during otoscopy. Individuals who reported hearing impairments such as reduced hearing and difficulty understanding noises demonstrated fewer responses in the DPOAEs at various frequencies. In addition, there were significant differences in DPOAE amplitudes among different age groups. Given the substantial burden of hearing loss with ageing, attention to this population is essential for the possibility of preventing or delaying hearing loss. Cancer patients entering a chemotherapy service have a hearing case history of risk factors and hearing alterations prior to exposure to potentially-ototoxic drugs.

Background: Olive leaves, a by-product of olive oil production, are rich in oleuropein, a phenolic compound with antioxidant and anti-inflammatory properties. This systematic review and meta-analysis evaluated the effects of olive leaf extract (OLE) and oleuropein on glucose metabolism, lipid profile, and inflammatory markers in randomized clinical trials (RCTs). Methods: The review was registered in PROSPERO (CRD42022375615) and followed PRISMA guidelines. PubMed, Scopus, and Web of Science were searched up to January 2026 without restrictions. Eligible studies were RCTs in adults comparing OLE or oleuropein with placebo or control. Study selection, data extraction, and risk of bias (RoB 2) assessment were performed independently by two reviewers; certainty of evidence was assessed with GRADE. Meta-analyses were conducted when at least two trials reported suitable data. Results: Eleven RCTs were included (4 short-term and 7 continuous-intake trials). Short-term crossover studies showed heterogeneous effects on postprandial glycemia and insulin responses, precluding meta-analysis. In continuous-intake, parallel-design RCTs, pooled analyses demonstrated no statistically or clinically significant effects on glycemic or lipid outcomes. Evidence regarding inflammatory markers was scarce and of low certainty. Conclusion: The current evidence does not support clinical recommendations for OLE supplementation aimed at health benefits. Data from methodologically consistent and robust trials indicate no statistically significant metabolic or inflammatory effects under usual human consumption patterns, whereas evidence from other study designs remains inconclusive. Further high-quality RCTs are required to clarify potential metabolic benefits.

Background: Viticulture in Southern Brazil heavily relies on fungicides, such as Mancozeb, to manage fungal diseases. Increasing concern has emerged regarding the chronic health effects of Mancozeb exposure among vineyard workers, particularly its potential to induce oxidative stress and genotoxicity. Methods: A cross-sectional study was conducted between July and November 2023 involving 94 participants: 50 vineyard workers occupationally exposed to Mancozeb and 44 organic farmers with no history of pesticide exposure, who served as the control group. Eligible participants were aged 18 years or older, and exposed individuals had at least 5 years of documented Mancozeb use. Data on demographics, health status, occupational history, and use of personal protective equipment (PPE) were collected through structured interviews. Blood and urine samples were analyzed to determine hematological and biochemical parameters, oxidative stress biomarkers, genotoxicity (via comet assay and micronucleus test), and urinary ethylene thiourea (ETU), the primary metabolite of Mancozeb. Results: Workers exposed to Mancozeb exhibited significantly elevated levels of oxidative stress markers (p < 0.001) and DNA damage in both genotoxicity assays (p < 0.001). Urinary ETU concentrations were also markedly elevated, and a threshold of 69.3 ng/mL was identified as a discriminative marker of exposure. Conclusions: This study offers a novel contribution by proposing a specific biological exposure limit for ETU concentrations, derived from ROC curve analysis, representing a significant advancement in occupational health. The findings underscore the urgent need for regulatory biological exposure limits and the implementation of effective preventive strategies.

The inhalation of pollutants from fossil fuel combustion increases oxidative stress and may cause genotoxic damage, a risk heightened during physical exercise due to increased respiratory rates. This concern extends to equines engaged in intense activities like show jumping. Antioxidant supplementation with vitamin E and selenium may mitigate oxidative stress induced by exercise in polluted environments. This study evaluated the effects of oral supplementation on show jumping horses subjected to physical exertion in urban (n = 10) and peri-urban (n = 10) areas with varying pollution levels. Oxidative stress markers (protein quantification, superoxide dismutase, catalase, and thiobarbituric acid reactive substances), marker of genomic instability (binucleation), and clinical parameters were assessed in relation to environmental nitrogen dioxide (NO₂) and ozone (O₃) levels. Results showed that supplementation influenced thiobarbituric acid reactive substances (TBARS), with lower malondialdehyde (MDA) concentration in supplemented groups, especially in urban horses (p = 0.027). DNA damage was reduced in supplemented horses from urban areas with high ozone (O₃) levels (p = 0.002), but no protective effect was observed in peri-urban horses. These findings suggest that vitamin E and selenium supplementation have antioxidant and DNA-protective impact in urban environments, though their efficacy appears variable in peri-urban areas. Further research incorporating additional pollution markers is necessary to clarify these effects.

Ototoxicity is the adverse reaction in the auditory system caused by exposure to xenobiotics. Animal models have been used to improve the understanding of ototoxicity research. Zebrafish (Danio rerio) is a model animal that is being increasingly used in ototoxicity research. Here, we identified and map the evidence on the use of zebrafish as an animal model to study ototoxicity. We conducted an exploratory systematic search in the three databases (Cochrane, LILACS and PubMed) with a two-step screening process based on inclusion/exclusion criteria. Outcome measures of included non-drug xenobiotics studies (n = 15) and drugs (n = 118) were grouped into: hair cell death rate, exposure time, and developmental stages. Our review evidences zebrafish as an important model to screen the ototoxicity potential of xenobiotics, but also demonstrates novel studies are necessary to define the most appropriate evaluation outcomes and specific protocol.