Pub Date : 2025-09-09DOI: 10.1016/j.etap.2025.104817
Kane Colston , Karen Mifsud , Nicola Rooney , Juan Manuel Grande , Irene Bueno
Asian vulture declines have been linked to the consumption of contaminated livestock carcasses with the non-steroidal anti-inflammatory (NSAID) diclofenac. Studies have suggested that the toxicity of NSAIDs to Old World vultures may be through an intronic premature termination codon (PTC) in the gene CYP2C19, encoding a cytochrome P450 enzyme thought responsible for diclofenac metabolism in vultures. However, it remains unclear whether this mechanism applies for all susceptible raptor species. We used nucleotide databases (NCBI) to compare the Cape vulture (Gyps coprotheres) CYP2C19 sequence to other vulture sequences to identify the presence of the intronic PTC. Our search revealed that only Gyps species possessed the CYP2C19 PTC. This is despite NSAID toxicity at similar contaminant levels found in non-Gyps accipitrid mortalities. Our findings suggest avian scavengers could be affected by additional toxicological mechanisms, including sublethal toxicity. Further research is required to establish such mechanisms and exposure risk in non-Gyps scavengers.
{"title":"Non-steroidal anti-inflammatory drugs (NSAIDs) as a hidden threat to scavenging raptors beyond Gyps: A call for wider research and surveillance","authors":"Kane Colston , Karen Mifsud , Nicola Rooney , Juan Manuel Grande , Irene Bueno","doi":"10.1016/j.etap.2025.104817","DOIUrl":"10.1016/j.etap.2025.104817","url":null,"abstract":"<div><div>Asian vulture declines have been linked to the consumption of contaminated livestock carcasses with the non-steroidal anti-inflammatory (NSAID) diclofenac. Studies have suggested that the toxicity of NSAIDs to Old World vultures may be through an intronic premature termination codon (PTC) in the gene CYP2C19, encoding a cytochrome P450 enzyme thought responsible for diclofenac metabolism in vultures. However, it remains unclear whether this mechanism applies for all susceptible raptor species. We used nucleotide databases (NCBI) to compare the Cape vulture (<em>Gyps coprotheres</em>) CYP2C19 sequence to other vulture sequences to identify the presence of the intronic PTC. Our search revealed that only <em>Gyps</em> species possessed the CYP2C19 PTC. This is despite NSAID toxicity at similar contaminant levels found in non-<em>Gyps</em> accipitrid mortalities. Our findings suggest avian scavengers could be affected by additional toxicological mechanisms, including sublethal toxicity. Further research is required to establish such mechanisms and exposure risk in non-<em>Gyps</em> scavengers.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104817"},"PeriodicalIF":4.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-02DOI: 10.1016/j.etap.2025.104815
Isis Coalova , Nancy Andrioli , Hugo March , María del Carmen Ríos de Molina , Gabriela Chaufan
The increasing global use of pesticides in crop pest control has raised concerns about toxic interactions. This study investigates the interaction between glyphosate and cypermethrin formulations concerning cell death and genotoxicity. Three models were applied to assess whether the combined effects were additive, antagonistic, or synergistic: "Linear Interaction Effect", "Combination Subthresholding," and "Cooperative Effect". Key indicators, such as apoptotic nuclei, caspase 3/7 activity, early and late apoptosis, micronuclei frequency, and mitotic abnormalities, were evaluated. Results showed synergistic effects on early and late apoptosis, as indicated by the "Linear Interaction Effect" model, while morphological apoptosis markers and micronuclei frequency displayed additive effects. Caspase 3/7 activity induction was synergistic, though no interaction was observed in the combination effect. These findings suggest that agrochemical mixtures cause more severe toxic effects than individual chemicals, emphasizing the need for mechanistic studies on common environmental contaminant mixtures.
{"title":"Assessment of cell death and genotoxic potential of glyphosate and cypermethrin formulations, individually and in combination, in HEp-2 cells","authors":"Isis Coalova , Nancy Andrioli , Hugo March , María del Carmen Ríos de Molina , Gabriela Chaufan","doi":"10.1016/j.etap.2025.104815","DOIUrl":"10.1016/j.etap.2025.104815","url":null,"abstract":"<div><div>The increasing global use of pesticides in crop pest control has raised concerns about toxic interactions. This study investigates the interaction between glyphosate and cypermethrin formulations concerning cell death and genotoxicity. Three models were applied to assess whether the combined effects were additive, antagonistic, or synergistic: \"Linear Interaction Effect\", \"Combination Subthresholding,\" and \"Cooperative Effect\". Key indicators, such as apoptotic nuclei, caspase 3/7 activity, early and late apoptosis, micronuclei frequency, and mitotic abnormalities, were evaluated. Results showed synergistic effects on early and late apoptosis, as indicated by the \"Linear Interaction Effect\" model, while morphological apoptosis markers and micronuclei frequency displayed additive effects. Caspase 3/7 activity induction was synergistic, though no interaction was observed in the combination effect. These findings suggest that agrochemical mixtures cause more severe toxic effects than individual chemicals, emphasizing the need for mechanistic studies on common environmental contaminant mixtures.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104815"},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.etap.2025.104814
Muhammad Kashif Ashraf , Sana Ullah , Muhamamd Bilal , Cristiana Roberta Multisanti , Caterina Faggio
The continuous increase in the concentration of heavy metals in bodies of water due to human activity poses a serious threat to the sustainability and overall health of the ecosystem. This study investigated the essential and toxic elements bioaccumulation in various tissues (gills, muscles, liver, and brain) of the Minor carp (Labeo gonius) from two sampling sites of highly polluted Khushab Lake, a tributary of River Jhelum (in the Pakistan's Punjab province), along with a less exposed reference site (Chashma Lake-less polluted site). The impacts of pollution on the health profile of the fish were assessed using multiple biomarkers for analysis. The maximum accumulation of essential and toxic elements was reported in liver tissues, followed by gills. Copper (Cu) and iron (Fe) were the highest accumulated essential elements in liver and gills tissues, while magnesium (Mg) and calcium (Ca) were the highest accumulated in muscles and brain tissues. Hematological and serum biochemical profile of L. gonius showed intense abnormalities at Khushab Lake as compared to reference site. Histopathological investigations indicated severe alterations in the liver tissues along with significant changes in other tissues. Principal component analysis (PCA) showed strong correlations among essential and toxic elements in various tissues of fish. The results revealed that aquatic life in Lake Khushab is at the greatest risk to its health. Therefore, mitigating measures should be adapted by key stakeholders including environmental protection agency (ensure disposal of pre-treated wastes and effluents) and fisheries department (limnological assessment and stocking of fish at regular intervals).
{"title":"Multi-biomarker assessment of essential and toxic elements accumulation in Labeo gonius from Khushab Lake (Pakistan)","authors":"Muhammad Kashif Ashraf , Sana Ullah , Muhamamd Bilal , Cristiana Roberta Multisanti , Caterina Faggio","doi":"10.1016/j.etap.2025.104814","DOIUrl":"10.1016/j.etap.2025.104814","url":null,"abstract":"<div><div>The continuous increase in the concentration of heavy metals in bodies of water due to human activity poses a serious threat to the sustainability and overall health of the ecosystem. This study investigated the essential and toxic elements bioaccumulation in various tissues (gills, muscles, liver, and brain) of the Minor carp (<em>Labeo gonius)</em> from two sampling sites of highly polluted Khushab Lake, a tributary of River Jhelum (in the Pakistan's Punjab province), along with a less exposed reference site (Chashma Lake-less polluted site). The impacts of pollution on the health profile of the fish were assessed using multiple biomarkers for analysis. The maximum accumulation of essential and toxic elements was reported in liver tissues, followed by gills. Copper (Cu) and iron (Fe) were the highest accumulated essential elements in liver and gills tissues, while magnesium (Mg) and calcium (Ca) were the highest accumulated in muscles and brain tissues. Hematological and serum biochemical profile of <em>L. gonius</em> showed intense abnormalities at Khushab Lake as compared to reference site. Histopathological investigations indicated severe alterations in the liver tissues along with significant changes in other tissues. Principal component analysis (PCA) showed strong correlations among essential and toxic elements in various tissues of fish. The results revealed that aquatic life in Lake Khushab is at the greatest risk to its health. Therefore, mitigating measures should be adapted by key stakeholders including environmental protection agency (ensure disposal of pre-treated wastes and effluents) and fisheries department (limnological assessment and stocking of fish at regular intervals).</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104814"},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-28DOI: 10.1016/j.etap.2025.104810
Shirui Liu , Simeng Yu , Yankun Huang , Jingyun Zhang , Kai Song , Shenbao Qu , Cixin Li , Aijiang Yang , Xia Hu
Di-(2-ethylhexyl) phthalate (DEHP) threatens human and wildlife health seriously, yet sex-dependent reproductive toxicity remains unclear. Therefore, in this study, we exposed zebrafish to various concentrations (0.01, 0.1, 1.0, and 2.0 mg/L) of DEHP for 28 days. Results indicate that DEHP exposure induced oxidative stress as a common response in both sexes and more pronounced reproductive toxicity to males than females. In males, sperm development stagnated at spermatogonia and enriched pathways were mainly associated with ribosome (Rps3, Rps27a) and endoplasmic reticulum stress(Hspa5). In females, oocyte development was affected at later stages and the pathways were mainly lipid metabolism and GnRH signaling pathway. Hub genes from PPI in females were Cacna2d3, Prkcba, Calm2a, Pla2g4aa in SCvsHigh while Pla2g4aa in SCvsLow. Overall, these findings provide new insights into the molecular mechanisms of DEHP toxicity, which is crucial for understanding its impact on reproductive health and ecological risk assessment.
{"title":"A transcriptomics-based analysis provides insights into the sex-dependent reproductive toxicity of DEHP in zebrafish (Danio rerio)","authors":"Shirui Liu , Simeng Yu , Yankun Huang , Jingyun Zhang , Kai Song , Shenbao Qu , Cixin Li , Aijiang Yang , Xia Hu","doi":"10.1016/j.etap.2025.104810","DOIUrl":"10.1016/j.etap.2025.104810","url":null,"abstract":"<div><div>Di-(2-ethylhexyl) phthalate (DEHP) threatens human and wildlife health seriously, yet sex-dependent reproductive toxicity remains unclear. Therefore, in this study, we exposed zebrafish to various concentrations (0.01, 0.1, 1.0, and 2.0 mg/L) of DEHP for 28 days. Results indicate that DEHP exposure induced oxidative stress as a common response in both sexes and more pronounced reproductive toxicity to males than females. In males, sperm development stagnated at spermatogonia and enriched pathways were mainly associated with ribosome (<em>Rps3</em>, <em>Rps27a</em>) and endoplasmic reticulum stress(<em>Hspa5</em>). In females, oocyte development was affected at later stages and the pathways were mainly lipid metabolism and GnRH signaling pathway. Hub genes from PPI in females were <em>Cacna2d3, Prkcba, Calm2a, Pla2g4aa</em> in SCvsHigh while <em>Pla2g4aa</em> in SCvsLow. Overall, these findings provide new insights into the molecular mechanisms of DEHP toxicity, which is crucial for understanding its impact on reproductive health and ecological risk assessment.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104810"},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-28DOI: 10.1016/j.etap.2025.104811
Didi Shan , Jianhua Liao , Yuxuan Zhu , Jia Yu , Jing Xu , Deyang Kong , Feng Ge
Fluorine-containing pesticides are widely applied in agriculture, yet their chronic ecotoxic effects on soil organisms remain understudied. This study evaluated the toxicity of three pesticides on Eisenia fetida through a 56-day soil exposure at gradient concentrations (fluxapyroxad:C1:62.5,C2:250, C3:1000 mg a.i./kg dry soil; fluopyram: C4:15.6, C5:62.5, C6:250 mg a.i./kg dry soil; bixafen: C7:125, C8:500, C9:1000 mg a.i./kg dry soil). Biomarkers of oxidative stress (ROS, MDA),antioxidant enzymes (SOD, CAT, GST), DNA damage (8-OHdG), mitochondrial function (SDH), and histopathology were assessed periodically. The results indicated that there was no significant difference in growth and reproduction between the low concentration groups and the control group(P > 0.05), while higher doses lead to weight loss (up to 40 % inhibition) and reduced offspring, likely due to energy depletion and reproductive organ damage. ROS and MDA increased dose- and time-dependently, with antioxidant enzymes showing initial activation followed by suppression, indicating antioxidant system failure. DNA damage (8-OHdG) escalated with concentration, linked to ROS overproduction. SDH activity declined significantly at high doses, reflecting mitochondrial dysfunction. Histopathology revealed epidermal shedding, intestinal damage, and seminal vesicle disorganization under high-exposure conditions. Integrated biomarker response (IBR) analysis confirmed dose-time-dependent toxicity, with maximal ecological risk in high-concentration groups. These findings highlight the mechanisms of fluorine-containing pesticide toxicity in earthworms, emphasizing their potential to disrupt soil ecosystems. This study provides critical data for ecological risk assessments of agrochemicals.
{"title":"Insights into the chronic toxicity and mechanisms of fluorine-containing pesticides on earthworms","authors":"Didi Shan , Jianhua Liao , Yuxuan Zhu , Jia Yu , Jing Xu , Deyang Kong , Feng Ge","doi":"10.1016/j.etap.2025.104811","DOIUrl":"10.1016/j.etap.2025.104811","url":null,"abstract":"<div><div>Fluorine-containing pesticides are widely applied in agriculture, yet their chronic ecotoxic effects on soil organisms remain understudied. This study evaluated the toxicity of three pesticides on <em>Eisenia fetida</em> through a 56-day soil exposure at gradient concentrations (fluxapyroxad:C1:62.5,C2:250, C3:1000 mg a.i./kg dry soil; fluopyram: C4:15.6, C5:62.5, C6:250 mg a.i./kg dry soil; bixafen: C7:125, C8:500, C9:1000 mg a.i./kg dry soil). Biomarkers of oxidative stress (ROS, MDA),antioxidant enzymes (SOD, CAT, GST), DNA damage (8-OHdG), mitochondrial function (SDH), and histopathology were assessed periodically. The results indicated that there was no significant difference in growth and reproduction between the low concentration groups and the control group(<em>P</em> > 0.05), while higher doses lead to weight loss (up to 40 % inhibition) and reduced offspring, likely due to energy depletion and reproductive organ damage. ROS and MDA increased dose- and time-dependently, with antioxidant enzymes showing initial activation followed by suppression, indicating antioxidant system failure. DNA damage (8-OHdG) escalated with concentration, linked to ROS overproduction. SDH activity declined significantly at high doses, reflecting mitochondrial dysfunction. Histopathology revealed epidermal shedding, intestinal damage, and seminal vesicle disorganization under high-exposure conditions. Integrated biomarker response (IBR) analysis confirmed dose-time-dependent toxicity, with maximal ecological risk in high-concentration groups. These findings highlight the mechanisms of fluorine-containing pesticide toxicity in earthworms, emphasizing their potential to disrupt soil ecosystems. This study provides critical data for ecological risk assessments of agrochemicals.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104811"},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-27DOI: 10.1016/j.etap.2025.104813
Alessandro F. Gualtieri , Serena Mirata , Mario Passalacqua , Anna Maria Bassi , Sonia Scarfì
This communication addresses the matter of the appropriate concentration metrics for the in vitro testing of mineral fibres, a specific technical issue affecting the correct determination of their toxic/carcinogenic potential. The exposure to certain mineral fibres (e.g., asbestos and erionite) is well-known for its detrimental effects on human health, with caution exposure limits set to 0.01 ff/cm3 by the European Council in 2023. In this regard, in vitro tests have a crucial role in the preliminary determination of the hazardous potential of mineral fibres, although selecting the appropriate concentration metrics and doses is currently controversial. Here, we address the complex technical issues of the current normalisation methods (i.e., mass normalization and fibre number normalization) with their advantages and disadvantages, ultimately concluding that mass normalisation should be recommended. In fact, considering two fibrous species with the same chemical composition, mass normalisation guarantees that the concentration of atomic species and ROS-inducing metals remains equal, while this parameter becomes an additional variable with fibre number normalisation.
{"title":"In vitro testing of hazardous mineral fibres: The issue of the concentration metric","authors":"Alessandro F. Gualtieri , Serena Mirata , Mario Passalacqua , Anna Maria Bassi , Sonia Scarfì","doi":"10.1016/j.etap.2025.104813","DOIUrl":"10.1016/j.etap.2025.104813","url":null,"abstract":"<div><div>This communication addresses the matter of the appropriate concentration metrics for the <em>in vitro</em> testing of mineral fibres, a specific technical issue affecting the correct determination of their toxic/carcinogenic potential. The exposure to certain mineral fibres (e.g., asbestos and erionite) is well-known for its detrimental effects on human health, with caution exposure limits set to 0.01 ff/cm<sup>3</sup> by the European Council in 2023. In this regard, <em>in vitro</em> tests have a crucial role in the preliminary determination of the hazardous potential of mineral fibres, although selecting the appropriate concentration metrics and doses is currently controversial. Here, we address the complex technical issues of the current normalisation methods (i.e., mass normalization and fibre number normalization) with their advantages and disadvantages, ultimately concluding that mass normalisation should be recommended. In fact, considering two fibrous species with the same chemical composition, mass normalisation guarantees that the concentration of atomic species and ROS-inducing metals remains equal, while this parameter becomes an additional variable with fibre number normalisation.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104813"},"PeriodicalIF":4.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-26DOI: 10.1016/j.etap.2025.104812
Loïc Angrand , Romain K. Gherardi , Guillemette Crépeaux
Aluminium-Based Adjuvants (ABAs) have been used in vaccines since the 1920s to boost immune responses. Despite their widespread use, their mechanisms of action remain only partially understood, and growing concerns exist about their long-term safety, particularly in vulnerable populations. This study examines the regulatory history of the aluminium content limit in vaccines and identifies major gaps in toxicological and epidemiological evaluation.
Through a detailed review of regulatory records, historical archives, Freedom of Information Act (FOIA) requests and responses, and scientific literature, we found that the current aluminium threshold of 0.85 mg per dose was set in the mid-20th century based on immunological efficacy - not on toxicological data- and remains in place despite changes in vaccination schedules and cumulative exposure. The key documents supporting this limit, which date back to 1947 and 1952, do not evaluate the potential toxicity of ABAs and are, in any case, no longer relevant to the current vaccination schedule.
There is an urgent need for independent pharmacokinetic and toxicological studies, transparent access to proprietary adjuvant compound, and a comeback to safer alternatives such as biocompatible calcium phosphate. Updating these standards is crucial for strengthening public confidence in vaccination policies.
{"title":"Regulatory limits of aluminium content of vaccines have not been set based on toxicological studies","authors":"Loïc Angrand , Romain K. Gherardi , Guillemette Crépeaux","doi":"10.1016/j.etap.2025.104812","DOIUrl":"10.1016/j.etap.2025.104812","url":null,"abstract":"<div><div>Aluminium-Based Adjuvants (ABAs) have been used in vaccines since the 1920s to boost immune responses. Despite their widespread use, their mechanisms of action remain only partially understood, and growing concerns exist about their long-term safety, particularly in vulnerable populations. This study examines the regulatory history of the aluminium content limit in vaccines and identifies major gaps in toxicological and epidemiological evaluation.</div><div>Through a detailed review of regulatory records, historical archives, Freedom of Information Act (FOIA) requests and responses, and scientific literature, we found that the current aluminium threshold of 0.85 mg per dose was set in the mid-20th century based on immunological efficacy - not on toxicological data- and remains in place despite changes in vaccination schedules and cumulative exposure. The key documents supporting this limit, which date back to 1947 and 1952, do not evaluate the potential toxicity of ABAs and are, in any case, no longer relevant to the current vaccination schedule.</div><div>There is an urgent need for independent pharmacokinetic and toxicological studies, transparent access to proprietary adjuvant compound, and a comeback to safer alternatives such as biocompatible calcium phosphate. Updating these standards is crucial for strengthening public confidence in vaccination policies.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104812"},"PeriodicalIF":4.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-26DOI: 10.1016/j.etap.2025.104800
Jorge A. Narvaez Pardo , Agustina Freire , Marina C. Muñoz , Bruno Buchholz , Analía L. Tomat , Mariela M. Gironacci , Ulrike M. Steckelings , Natalia D. Magnani , Pablo A. Evelson , Fernando P. Dominici
The impact of chronic exposure to urban air (UA) on renin-angiotensin system (RAS) components and the therapeutic potential of the angiotensin type 2 receptor (AT2R) agonist, Compound 21 (C21), in mitigating pollution-induced inflammation and oxidative stress was evaluated in a mouse model exposed to UA for 14 weeks. Air pollution exposure increased pro-inflammatory cytokines and oxidative damage markers in the lungs and kidneys and upregulated angiotensin converting enzyme; ACE, and angiotensin type 1 receptor; AT1R in the lungs; while it induced a compensatory increase in Mas receptor; MasR and AT2R in the heart and kidneys. C21 treatment reduced IL-1β and TNF-α expression in the lungs and 3-nitrotyrosine levels in the lungs and kidneys, downregulated both ACE and AT1R expression in the lungs and increased renal MasR expression. Current results underscore the relevance of RAS dysregulation in pollution-induced tissue damage and positions AT2R agonism as a possibility for mitigating the health impacts of air pollution.
{"title":"Angiotensin II type 2 receptor activation alleviates inflammation and oxidative stress caused by chronic exposure to air pollution","authors":"Jorge A. Narvaez Pardo , Agustina Freire , Marina C. Muñoz , Bruno Buchholz , Analía L. Tomat , Mariela M. Gironacci , Ulrike M. Steckelings , Natalia D. Magnani , Pablo A. Evelson , Fernando P. Dominici","doi":"10.1016/j.etap.2025.104800","DOIUrl":"10.1016/j.etap.2025.104800","url":null,"abstract":"<div><div>The impact of chronic exposure to urban air (UA) on renin-angiotensin system (RAS) components and the therapeutic potential of the angiotensin type 2 receptor (AT<sub>2</sub>R) agonist, Compound 21 (C21), in mitigating pollution-induced inflammation and oxidative stress was evaluated in a mouse model exposed to UA for 14 weeks. Air pollution exposure increased pro-inflammatory cytokines and oxidative damage markers in the lungs and kidneys and upregulated angiotensin converting enzyme; ACE, and angiotensin type 1 receptor; AT<sub>1</sub>R in the lungs; while it induced a compensatory increase in Mas receptor; MasR and AT<sub>2</sub>R in the heart and kidneys. C21 treatment reduced IL-1β and TNF-α expression in the lungs and 3-nitrotyrosine levels in the lungs and kidneys, downregulated both ACE and AT<sub>1</sub>R expression in the lungs and increased renal MasR expression. Current results underscore the relevance of RAS dysregulation in pollution-induced tissue damage and positions AT<sub>2</sub>R agonism as a possibility for mitigating the health impacts of air pollution.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104800"},"PeriodicalIF":4.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1016/j.etap.2025.104801
Priscilla Dantas de Souza Ventura , Daniel Vitor de Souza , Anna Caroline C. Aguiar , Carolina P.F. Carvalho , Daniel A. Ribeiro , Marcia R. Nagaoka , Marcos L. Gazarini
The genus Plasmodium is responsible for malaria infection and promoting an accumulation of hemozoin followed by the generation of oxidizing species in the liver that is involved in hepatic damage. In this context, we performed the histopathological analysis in the mice liver infected with Plasmodium chabaudi treated orally with the antimalarial chloroquine, captopril (ACE I inhibitor), losartan (AT1 receptor blocker). In hematoxylin and eosin-stained liver sections, histopathological changes, such as sinusoid congestion, leukocyte infiltration, hemozoin deposition, portal tract inflammation, and metanuclear analysis were evaluated. The histopathological analysis shows a beneficial effect of chloroquine treatment alone or in combination with vasodilator treatments, reducing the score for each tissue change. Our data show that Plasmodium chabaudi infection compromises some hepatic histopathological parameters, and interestingly the treatment with vasodilators improved some of these alterations. Particularly, captopril reduces cytotoxicity induced by malaria infection in mouse liver cells.
{"title":"Captopril reduces liver cytotoxicity in a murine model of Plasmodium chabaudi infection","authors":"Priscilla Dantas de Souza Ventura , Daniel Vitor de Souza , Anna Caroline C. Aguiar , Carolina P.F. Carvalho , Daniel A. Ribeiro , Marcia R. Nagaoka , Marcos L. Gazarini","doi":"10.1016/j.etap.2025.104801","DOIUrl":"10.1016/j.etap.2025.104801","url":null,"abstract":"<div><div>The genus Plasmodium is responsible for malaria infection and promoting an accumulation of hemozoin followed by the generation of oxidizing species in the liver that is involved in hepatic damage. In this context, we performed the histopathological analysis in the mice liver infected with <em>Plasmodium chabaudi</em> treated orally with the antimalarial chloroquine, captopril (ACE I inhibitor), losartan (AT1 receptor blocker). In hematoxylin and eosin-stained liver sections, histopathological changes, such as sinusoid congestion, leukocyte infiltration, hemozoin deposition, portal tract inflammation, and metanuclear analysis were evaluated. The histopathological analysis shows a beneficial effect of chloroquine treatment alone or in combination with vasodilator treatments, reducing the score for each tissue change. Our data show that <em>Plasmodium chabaudi</em> infection compromises some hepatic histopathological parameters, and interestingly the treatment with vasodilators improved some of these alterations. Particularly, captopril reduces cytotoxicity induced by malaria infection in mouse liver cells.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"119 ","pages":"Article 104801"},"PeriodicalIF":4.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1016/j.etap.2025.104802
Carolina Panis , Altair Rodrigues Pires de Paula Filho , Stephen Flint Smith , José Oviedo , Marla Karine Amarante , Virginia Concato , Wander Rogério Pavanelli , Marcelo Estevam , Renata Santos Rabelo , Ohanna Maria Menezes Madeiro da Costa , Maiara Ferreira Terra , Bernardo Lemos
Glyphosate and atrazine, two widely used herbicides, may induce subtle molecular changes even at low levels encountered in the drinking water of some populations. This study assessed structural and RNA expression changes in MCF-7 and MDA-MB-231 breast cancer cell lines after 72-h exposures to glyphosate (50 or 500 ppb) and atrazine (2 or 20 ppb). These doses are commonly found in drinking water and falls below or within the maximum residue levels recommended or allowed in the drinking water of populations in Brazil and the USA. Genome wide RNA sequencing detected differentially expressed genes (DEGs) at lower doses as well as highlighted dose-dependent responses at higher concentrations. For instance, MDA-MB-231 cells treated with 20 ppb atrazine exhibited 60 DEGs, while 500 ppb glyphosate exposure resulted in 39 DEGs, with notable overlap in gene expression profiles across pesticides and doses. Gene set enrichment analysis suggested alterations linked to DNA repair and replication, sterol metabolism, and cellular response to starvation, with specific pathways varying by pesticide and cell line. Significant changes were observed in DNA homologous repair genes for both pesticides and cell lines. Finally, fourier-transform infrared spectroscopy (FTIR) suggested dose- and pesticide-specific structural changes linked to lipid metabolism and nucleic acid modifications. Our findings indicate that low-level glyphosate and atrazine exposures induce subtle structural and transcriptomic changes without overt cytotoxicity. These results underscore the potential implications for chronic environmental herbicide exposures that may affect breast cancer cell development and progression. Our study highlight the need for monitoring exposure in certain populations and for further investigations into the long-term consequences of pesticide exposure for human health.
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