Gokul Sudhakaran, Karthikeyan Ramamurthy, V N Dhaareshwar, R Rajakrishnan, Ahmed Alfarhan, Jesu Arockiaraj
{"title":"Liquid mosquito repellent induces toxic effects in zebrafish.","authors":"Gokul Sudhakaran, Karthikeyan Ramamurthy, V N Dhaareshwar, R Rajakrishnan, Ahmed Alfarhan, Jesu Arockiaraj","doi":"10.1080/01480545.2024.2436511","DOIUrl":null,"url":null,"abstract":"<p><p>Mosquitoes serve as vectors for life-threatening parasitic diseases, presenting a continuous threat throughout human history. This has resulted in the extensive utilization of various mosquito repellents, including liquid mosquito repellents (LMRs), roll-ons, and topical creams. While these products demonstrate significant efficacy, the toxicological implications associated with their use are not yet fully understood and continue to be a subject of debate. The analysis conducted using gas chromatography-mass spectrometry (GC-MS) on LMR revealed the presence of 158 distinct compounds, among which were Piperazine 2,5-dimethyl propyl and a range of hydrocarbons. The analysis of network toxicology indicated that 78 of the examined compounds contravened Lipinski's rule of five and exhibited considerable overlap with target genes associated with lung cancer pathways, thereby highlighting potential concerns regarding their carcinogenic properties. The exposure of zebrafish embryos to LMR concentrations between 0.1 and 14 µg/mL resulted in developmental toxicity assays that demonstrated a dose-dependent escalation in mortality rates and the occurrence of morphological abnormalities, such as pericardial edema and skeletal deformities. Behavioral assays demonstrated a marked decrease in locomotor activity at elevated LMR concentrations, indicating potential neurotoxic effects. Biochemical analyses revealed elevated levels of reactive oxygen species (ROS), enhanced lipid peroxidation, and diminished glutathione, which are indicative of oxidative stress. Enzyme activity assays indicated a reduction in superoxide dismutase (SOD) and catalase (CAT) activities, alongside an increase in lactate dehydrogenase (LDH) activity, which suggests the occurrence of cellular damage. Analysis of gene expression demonstrated significant dysregulation in genes associated with oxidative stress (SOD1, CAT), inflammatory markers (TNF-α, IL-1β), apoptotic regulators (p53, bcl2), and neurobiological genes (brain-derived neurotrophic factor, bdnf). The results highlight the possible health hazards linked to LMR exposure, which manifest as developmental, biochemical, and genetic alterations in zebrafish embryos.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.1000,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug and Chemical Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01480545.2024.2436511","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Mosquitoes serve as vectors for life-threatening parasitic diseases, presenting a continuous threat throughout human history. This has resulted in the extensive utilization of various mosquito repellents, including liquid mosquito repellents (LMRs), roll-ons, and topical creams. While these products demonstrate significant efficacy, the toxicological implications associated with their use are not yet fully understood and continue to be a subject of debate. The analysis conducted using gas chromatography-mass spectrometry (GC-MS) on LMR revealed the presence of 158 distinct compounds, among which were Piperazine 2,5-dimethyl propyl and a range of hydrocarbons. The analysis of network toxicology indicated that 78 of the examined compounds contravened Lipinski's rule of five and exhibited considerable overlap with target genes associated with lung cancer pathways, thereby highlighting potential concerns regarding their carcinogenic properties. The exposure of zebrafish embryos to LMR concentrations between 0.1 and 14 µg/mL resulted in developmental toxicity assays that demonstrated a dose-dependent escalation in mortality rates and the occurrence of morphological abnormalities, such as pericardial edema and skeletal deformities. Behavioral assays demonstrated a marked decrease in locomotor activity at elevated LMR concentrations, indicating potential neurotoxic effects. Biochemical analyses revealed elevated levels of reactive oxygen species (ROS), enhanced lipid peroxidation, and diminished glutathione, which are indicative of oxidative stress. Enzyme activity assays indicated a reduction in superoxide dismutase (SOD) and catalase (CAT) activities, alongside an increase in lactate dehydrogenase (LDH) activity, which suggests the occurrence of cellular damage. Analysis of gene expression demonstrated significant dysregulation in genes associated with oxidative stress (SOD1, CAT), inflammatory markers (TNF-α, IL-1β), apoptotic regulators (p53, bcl2), and neurobiological genes (brain-derived neurotrophic factor, bdnf). The results highlight the possible health hazards linked to LMR exposure, which manifest as developmental, biochemical, and genetic alterations in zebrafish embryos.
期刊介绍:
Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal.
Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.