Pub Date : 2025-12-01Epub Date: 2025-10-30DOI: 10.1016/j.etap.2025.104859
Wei Zhang , Hui Chen , Yanshu Li , Qian Zhu , Kangtai Liu , Xinran Liu , Yan Wang , Gaochun Zhu
Lead (Pb) facilitates neurological deficits. Silybin is a flavonoid with neuroprotective properties. Heterogeneous nuclear ribonucleoprotein U (hnRNP U) has been implicated in neurodevelopmental disorders and predicted to regulate Repressor Element-1 Silencing Transcription (REST) expression. STAT3 can form a complex with hnRNP U and is inhibited by Silybin. We aim to elucidate the role of hnRNP U/STAT3 in Pb neurotoxicity and the neuroprotective effects of Silybin in Pb-exposed rats. We found that Pb increased the nuclear protein levels of hnRNP U and STAT3 and REST expression, which Silybin can partially reverse. Silencing hnRNP U reduced REST expression. Inhibiting STAT3 blocked hnRNP U nuclear transport. Silybin improves Pb-induced learning and memory impairment. Silybin reduced the expression of hnRNP U and NFκB. Inhibiting NFκB reduced hnRNP U expression. These suggest that Silybin improves Pb-induced learning and memory impairment by antagonizing STAT3/hnRNP U/REST and hnRNP U/NFκB.
{"title":"Silybin ameliorates Pb-induced learning and memory impairment by inhibiting STAT3/hnRNP U/REST and NFκB/hnRNP U","authors":"Wei Zhang , Hui Chen , Yanshu Li , Qian Zhu , Kangtai Liu , Xinran Liu , Yan Wang , Gaochun Zhu","doi":"10.1016/j.etap.2025.104859","DOIUrl":"10.1016/j.etap.2025.104859","url":null,"abstract":"<div><div>Lead (Pb) facilitates neurological deficits. Silybin is a flavonoid with neuroprotective properties. Heterogeneous nuclear ribonucleoprotein U (hnRNP U) has been implicated in neurodevelopmental disorders and predicted to regulate Repressor Element-1 Silencing Transcription (REST) expression. STAT3 can form a complex with hnRNP U and is inhibited by Silybin. We aim to elucidate the role of hnRNP U/STAT3 in Pb neurotoxicity and the neuroprotective effects of Silybin in Pb-exposed rats. We found that Pb increased the nuclear protein levels of hnRNP U and STAT3 and REST expression, which Silybin can partially reverse. Silencing hnRNP U reduced REST expression. Inhibiting STAT3 blocked hnRNP U nuclear transport. Silybin improves Pb-induced learning and memory impairment. Silybin reduced the expression of hnRNP U and NFκB. Inhibiting NFκB reduced hnRNP U expression. These suggest that Silybin improves Pb-induced learning and memory impairment by antagonizing STAT3/hnRNP U/REST and hnRNP U/NFκB.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104859"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396813","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}
Coastal ecosystems are highly exposed to cadmium (Cd), a widespread heavy metal with multifaceted toxicity. This study investigates the early cellular responses of Mytilus galloprovincialis exposed to two hazardous Cd concentrations (0.1 and 1 µM) for 4 days. Digestive gland analyses revealed a dose-dependent modulation of key stress biomarkers. Gene expression was quantified for proteins involved in folding (HSP90, HSP70, HSP27, HSP26, calreticulin, FKBP) and metal detoxification (metallothionein-10 and −20; MT-10, MT-20). Oxidative stress responses included catalase (CAT) and glutathione S-transferase (GST) activities, malondialdehyde (MDA) levels, and protein sulfhydryls (PSH), while MT levels were also measured. The results show a coordinated upregulation of chaperones and antioxidant defenses, reflecting an adaptive strategy to Cd-induced stress. Although these biomarkers are not specific to cadmium, their integrated responses provide mechanistic insight into early cellular perturbations, highlighting their potential value for biomarker-based environmental monitoring in coastal ecosystems.
{"title":"Unraveling the molecular mechanisms of cadmium-induced stress in Mytilus galloprovincialis: Chaperone proteins as key mediators","authors":"Khouloud Boukadida , Mohamed Banni , Tiziana Cappello , Marouane Chemek , Imed Messaoudi , Hamadi Boussetta","doi":"10.1016/j.etap.2025.104847","DOIUrl":"10.1016/j.etap.2025.104847","url":null,"abstract":"<div><div>Coastal ecosystems are highly exposed to cadmium (Cd), a widespread heavy metal with multifaceted toxicity. This study investigates the early cellular responses of <em>Mytilus galloprovincialis</em> exposed to two hazardous Cd concentrations (0.1 and 1 µM) for 4 days. Digestive gland analyses revealed a dose-dependent modulation of key stress biomarkers. Gene expression was quantified for proteins involved in folding (HSP90, HSP70, HSP27, HSP26, calreticulin, FKBP) and metal detoxification (metallothionein-10 and −20; MT-10, MT-20). Oxidative stress responses included catalase (CAT) and glutathione S-transferase (GST) activities, malondialdehyde (MDA) levels, and protein sulfhydryls (PSH), while MT levels were also measured. The results show a coordinated upregulation of chaperones and antioxidant defenses, reflecting an adaptive strategy to Cd-induced stress. Although these biomarkers are not specific to cadmium, their integrated responses provide mechanistic insight into early cellular perturbations, highlighting their potential value for biomarker-based environmental monitoring in coastal ecosystems.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104847"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314388","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}
Crayfish has been used in biomedical research due to their adaptability and resistance. While genetics, molecular biology, behavior assessments, electrophysiology, and microscopy techniques have been employed to study these crustaceans, in vivo metabolic evaluations using imaging techniques remain scarce. From this perspective, the use of micro positron emission tomography (MicroPET) imaging in crustacean models represents a novel approach to understand metabolic processes in these organisms and evaluating potential environmental impacts on aquatic species.
Objective
To assess the regional uptake of [18F]FDG in male and female crayfish using MicroPET imaging and to find the optimal scan acquisition time.
Methods
Adult male and female crayfish (n = 10/sex, 30–40 g) underwent 1-hour MicroPET scans (6 frames of 10 min) after administration of [18F]FDG (7.4 ± 1.2 MBq). Standardized uptake values (SUV) were calculated for the brain, gonads, green gland, heart, and ganglia of ventral nerve cord.
Results
The brain, green gland, and subesophageal ganglion exhibited the highest metabolic activity. Significant differences in [18F]FDG uptake related to sex were observed only in the gonads, with females showing higher uptake than males. No significant differences were found in other structures; nevertheless, male crayfish showed a higher coefficient of variation (44.33–92.7 %) than females (13.11–46.55 %). Exploratory inter-structure correlation analysis showed uniformly high coupling along the ventral nerve cord in both sexes, with males exhibiting stronger coordination between the heart/green gland and abdominal ganglia (Δρ up to ∼0.8), suggesting sex-dependent metabolic integration.
Conclusions
MicroPET imaging is a valuable tool for assessing metabolic activity and sexual dimorphism in crayfish in a single 10-minute scan (40 min after dose administration). These findings provide a groundwork for further studies investigating the physiological and biochemical basis of these differences.
{"title":"Whole-body glucose uptake in crayfish (Procambarus clarkii): A study of sexual dimorphism via [18F]FDG MicroPET imaging","authors":"Arturo Avendaño-Estrada , Miguel Angel Avila-Rodríguez , Jesús Hernández-Falcón , Karina Mendoza-Ángeles","doi":"10.1016/j.etap.2025.104849","DOIUrl":"10.1016/j.etap.2025.104849","url":null,"abstract":"<div><div>Crayfish has been used in biomedical research due to their adaptability and resistance. While genetics, molecular biology, behavior assessments, electrophysiology, and microscopy techniques have been employed to study these crustaceans, <em>in vivo</em> metabolic evaluations using imaging techniques remain scarce. From this perspective, the use of micro positron emission tomography (MicroPET) imaging in crustacean models represents a novel approach to understand metabolic processes in these organisms and evaluating potential environmental impacts on aquatic species.</div></div><div><h3>Objective</h3><div>To assess the regional uptake of [<sup>18</sup>F]FDG in male and female crayfish using MicroPET imaging and to find the optimal scan acquisition time.</div></div><div><h3>Methods</h3><div>Adult male and female crayfish (n = 10/sex, 30–40 g) underwent 1-hour MicroPET scans (6 frames of 10 min) after administration of [<sup>18</sup>F]FDG (7.4 ± 1.2 MBq). Standardized uptake values (SUV) were calculated for the brain, gonads, green gland, heart, and ganglia of ventral nerve cord.</div></div><div><h3>Results</h3><div>The brain, green gland, and subesophageal ganglion exhibited the highest metabolic activity. Significant differences in [<sup>18</sup>F]FDG uptake related to sex were observed only in the gonads, with females showing higher uptake than males. No significant differences were found in other structures; nevertheless, male crayfish showed a higher coefficient of variation (44.33–92.7 %) than females (13.11–46.55 %). Exploratory inter-structure correlation analysis showed uniformly high coupling along the ventral nerve cord in both sexes, with males exhibiting stronger coordination between the heart/green gland and abdominal ganglia (Δρ up to ∼0.8), suggesting sex-dependent metabolic integration.</div></div><div><h3>Conclusions</h3><div>MicroPET imaging is a valuable tool for assessing metabolic activity and sexual dimorphism in crayfish in a single 10-minute scan (40 min after dose administration). These findings provide a groundwork for further studies investigating the physiological and biochemical basis of these differences.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104849"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338429","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}
This study examined the association between ambient air pollution and risk of rheumatoid arthritis (RA). Individuals born 1960–1999 from the nationwide Danish Occupational Cohort with eXposure data were linked to modeled exposure at the home address(es) and RA hospital diagnoses (N = 2,092,596). Recent and 10-years cumulative exposure to particles ≤ 2.5 (PM2.5) and ≤ 10 µm (PM10), nitrogen oxide (NO2) and elemental carbon (EC) were subdivided into quartiles, and risk of incident RA (1997–2018) were calculated using Poisson regression analyses. Recent and cumulative exposure to PM2.5, NO2 and EC increased risk of RA, for all quartiles compared to the lowest quartile, but without a clear exposure-response relationship. Analyses stratified on sex generally showed similar trends, yet small differences were seen for PM2.5 and EC (differences between IRR for men and women in model 2: PM2.5 0.03–0.19, and EC 0.05–0.14). Higher risks were indicated for exposure to PM2.5 and PM10 for age below as compared to above 40 years. In conclusion, exposure to PM2.5, NO2 and EC increased risk of RA, with little influence from sex and some influence of age.
{"title":"Air pollution and risk of rheumatoid arthritis – A Danish register-based cohort study","authors":"Regitze Sølling Wils , Helena Breth Nielsen , Esben Meulengracht Flachs , Astrid Juhl Andersen , Lene Wohlfahrt Dreyer , Matthias Ketzel , Jørgen Brandt , Jibran Khan , Ulla Vogel , Camilla Sandal Sejbaek , Karin Sørig Hougaard","doi":"10.1016/j.etap.2025.104855","DOIUrl":"10.1016/j.etap.2025.104855","url":null,"abstract":"<div><div>This study examined the association between ambient air pollution and risk of rheumatoid arthritis (RA). Individuals born 1960–1999 from the nationwide Danish Occupational Cohort with eXposure data were linked to modeled exposure at the home address(es) and RA hospital diagnoses (N = 2,092,596). Recent and 10-years cumulative exposure to particles ≤ 2.5 (PM<sub>2.5</sub>) and ≤ 10 µm (PM<sub>10</sub>), nitrogen oxide (NO<sub>2</sub>) and elemental carbon (EC) were subdivided into quartiles, and risk of incident RA (1997–2018) were calculated using Poisson regression analyses. Recent and cumulative exposure to PM<sub>2.5</sub>, NO<sub>2</sub> and EC increased risk of RA, for all quartiles compared to the lowest quartile, but without a clear exposure-response relationship. Analyses stratified on sex generally showed similar trends, yet small differences were seen for PM2.5 and EC (differences between IRR for men and women in model 2: PM2.5 0.03–0.19, and EC 0.05–0.14). Higher risks were indicated for exposure to PM<sub>2.5</sub> and PM<sub>10</sub> for age below as compared to above 40 years. In conclusion, exposure to PM<sub>2.5</sub>, NO<sub>2</sub> and EC increased risk of RA, with little influence from sex and some influence of age.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104855"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359319","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}
This study aimed to investigate the effects of the herbicide 2,4-D dimethylammonium on hybrid catfish at a sub-lethal concentration by evaluating key post-exposure responses, including acetylcholinesterase (AChE) gene expression, hematological profiles, and histological alterations.
Results
AChE gene expression was characterized using RT-PCR, yielding product sizes of 489 bp for brain tissue and 470 bp for gill tissue. 2,4-D dimethylammonium impacted the cumulative mortality rates, AChE gene expression, blood cell quantity and morphology. Histological revealed that exposure led to degeneration of neurons and vacuolar changes in brain tissue, and partial fusion of lamellae, blood congestion, edema, and hyperplasia in gill tissue.
Conclusion
Exposure to 2,4-D dimethylammonium at sub-lethal concentrations led to significant effects on AChE gene expression, blood cell counts and histological alterations hybrid catfish. These findings highlight the importance of monitoring and regulating herbicide use to mitigate potential long-term impacts on aquatic life, as well as human health.
{"title":"2,4-D dimethylammonium toxicity in hybrid catfish: Acetylcholinesterase gene, hematology and histology","authors":"Sugunya Kumla , Phochit Nanthanawat , Jakkaphun Nanuam , Pongpat Kiatprasert , Amnuay Wattanakornsiri , Chutima Thanomsit","doi":"10.1016/j.etap.2025.104867","DOIUrl":"10.1016/j.etap.2025.104867","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effects of the herbicide 2,4-D dimethylammonium on hybrid catfish at a sub-lethal concentration by evaluating key post-exposure responses, including acetylcholinesterase (AChE) gene expression, hematological profiles, and histological alterations.</div></div><div><h3>Results</h3><div>AChE gene expression was characterized using RT-PCR, yielding product sizes of 489 bp for brain tissue and 470 bp for gill tissue. 2,4-D dimethylammonium impacted the cumulative mortality rates, AChE gene expression, blood cell quantity and morphology. Histological revealed that exposure led to degeneration of neurons and vacuolar changes in brain tissue, and partial fusion of lamellae, blood congestion, edema, and hyperplasia in gill tissue.</div></div><div><h3>Conclusion</h3><div>Exposure to 2,4-D dimethylammonium at sub-lethal concentrations led to significant effects on AChE gene expression, blood cell counts and histological alterations hybrid catfish. These findings highlight the importance of monitoring and regulating herbicide use to mitigate potential long-term impacts on aquatic life, as well as human health.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104867"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531054","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 : 2025-12-01Epub Date: 2025-11-14DOI: 10.1016/j.etap.2025.104869
Noor Muhammad Khan , Arpita Vyas , Mohammad Ghasemzadeh-Hasankolaei , Vasantha Padmanabhan , Neil P. Evans , Michelle Bellingham
Cardiovascular disease (CVD) is a major sexually dimorphic cause of mortality and morbidity. Prenatal exposure to environmental chemicals (ECs) can program the adult onset of CVD. Using a real-life EC exposure sheep model, this study investigated structural and molecular underpinnings of the sex-specific effects of prenatal EC mixture exposure via mothers grazing on biosolids treated pasture (BTP) in left ventricular (LV) tissues. EC mixture exposure had no impact on plasma TG and TC levels, LV cardiomyocyte number or collagen scoring in both sexes. However, a significant increase (P < 0.05) in fibrosis was evident in interstitial, perivascular and replacement fibrosis in BTP males. A significant upregulation of inflammatory (MHC-DRB1, MHC-DYA), apoptosis (CASP3) markers, together with elevated IGF-1 and IGF1-R expression was restricted to EC exposed males only. These findings extend our earlier results on sex-specific differences in prenatal EC exposure programming of adult CV functioning, particularly in males.
{"title":"Sexually dimorphic effects of in-utero exposure to a real-life environmental chemical mixture on markers of cardiovascular function in adult sheep","authors":"Noor Muhammad Khan , Arpita Vyas , Mohammad Ghasemzadeh-Hasankolaei , Vasantha Padmanabhan , Neil P. Evans , Michelle Bellingham","doi":"10.1016/j.etap.2025.104869","DOIUrl":"10.1016/j.etap.2025.104869","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) is a major sexually dimorphic cause of mortality and morbidity. Prenatal exposure to environmental chemicals (ECs) can program the adult onset of CVD. Using a real-life EC exposure sheep model, this study investigated structural and molecular underpinnings of the sex-specific effects of prenatal EC mixture exposure via mothers grazing on biosolids treated pasture (BTP) in left ventricular (LV) tissues. EC mixture exposure had no impact on plasma TG and TC levels, LV cardiomyocyte number or collagen scoring in both sexes. However, a significant increase (P < 0.05) in fibrosis was evident in interstitial, perivascular and replacement fibrosis in BTP males. A significant upregulation of inflammatory (MHC-DRB1, MHC-DYA), apoptosis (CASP3) markers, together with elevated IGF-1 and IGF1-R expression was restricted to EC exposed males only. These findings extend our earlier results on sex-specific differences in prenatal EC exposure programming of adult CV functioning, particularly in males.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104869"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531340","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}
Acute radiation exposure causes severe colonic damage and gastrointestinal (GI) syndrome. Although cystine and theanine (CT) may ameliorate 5 Gy X-ray (0.5531 Gy/min) radiation-induced damage of CT-treated rats (280 mg/kg for 5 days), their precise mechanisms in protecting colonic crypt cells and maintaining epithelial integrity remain unclear. Using a rat model of radiation-induced GI injury following 8–14 Gy exposure, we explored CT treatment effects on crypt survival, apoptosis, DNA damage, and inflammation. CT treatment eliminated bloody diarrhea (p = 0.0075) and decreased ulceration to 6.5 % compared to 35.1 % in controls (p < 0.01). Living crypt increased to 86.7 % from 37.7 % in controls (p < 0.01) at 10 Gy exposure. CT enhanced genomic stability by reducing γ-H2AX foci formations and pyroptotic cell death mediated by AIM2 inflammasome activation, including stem cells. CT treatment enhances crypt survival and limits apoptosis/pyroptosis in radiation-induced GI syndrome, indicating radioprotective potential.
{"title":"Protective effects of cystine and theanine on radiation-induced gastrointestinal syndrome: Modulation of apoptosis, pyroptosis, and crypt survival","authors":"Kazuko Shichijo , Mutsumi Matsuu-Matsuyama , Takashi Tsuchiya , Hisayoshi Kondo , Ichiro Sekine","doi":"10.1016/j.etap.2025.104848","DOIUrl":"10.1016/j.etap.2025.104848","url":null,"abstract":"<div><div>Acute radiation exposure causes severe colonic damage and gastrointestinal (GI) syndrome. Although cystine and theanine (CT) may ameliorate 5 Gy X-ray (0.5531 Gy/min) radiation-induced damage of CT-treated rats (280 mg/kg for 5 days), their precise mechanisms in protecting colonic crypt cells and maintaining epithelial integrity remain unclear. Using a rat model of radiation-induced GI injury following 8–14 Gy exposure, we explored CT treatment effects on crypt survival, apoptosis, DNA damage, and inflammation. CT treatment eliminated bloody diarrhea (<em>p</em> = 0.0075) and decreased ulceration to 6.5 % compared to 35.1 % in controls (<em>p</em> < 0.01). Living crypt increased to 86.7 % from 37.7 % in controls (<em>p</em> < 0.01) at 10 Gy exposure. CT enhanced genomic stability by reducing γ-H2AX foci formations and pyroptotic cell death mediated by AIM2 inflammasome activation, including stem cells. CT treatment enhances crypt survival and limits apoptosis/pyroptosis in radiation-induced GI syndrome, indicating radioprotective potential.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104848"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331407","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 : 2025-12-01Epub Date: 2025-10-30DOI: 10.1016/j.etap.2025.104860
Claudia Moyano-López, Paula Llorens, Ana Juan-García, Cristina Juan
Beauvericin (BEA) and patulin (PAT) are foodborne mycotoxins with known cytotoxic effects, but their combined impact on neuronal cells is unclear. This study evaluates the individual and interactive neurotoxic effects of BEA and PAT in undifferentiated SH-SY5Y human neuroblastoma cells for 24 h and 48 h, focusing on oxidative stress, lipid peroxidation (LPO), cell cycle progression, and cell death. Both toxins increased reactive oxygen species (ROS), with greater levels under co-exposure, while LPO was mainly elevated by individual treatments. Combined exposure led to cell cycle arrest, characterized by SubG1 accumulation and reduction in S and M phases. Apoptosis and necrosis varied with time and dose, with co-exposure favoring late apoptosis and necrosis. These results demonstrate that BEA and PAT act an enhanced manner through oxidative and cell cycle–related mechanisms, underscoring the importance of considering co-exposures in neurotoxicity risk assessment.
{"title":"ROS-mediated cytotoxicity and cell death pathways in SH-SY5Y cells exposed to beauvericin, patulin, and their combination","authors":"Claudia Moyano-López, Paula Llorens, Ana Juan-García, Cristina Juan","doi":"10.1016/j.etap.2025.104860","DOIUrl":"10.1016/j.etap.2025.104860","url":null,"abstract":"<div><div>Beauvericin (BEA) and patulin (PAT) are foodborne mycotoxins with known cytotoxic effects, but their combined impact on neuronal cells is unclear. This study evaluates the individual and interactive neurotoxic effects of BEA and PAT in undifferentiated SH-SY5Y human neuroblastoma cells for 24 h and 48 h, focusing on oxidative stress, lipid peroxidation (LPO), cell cycle progression, and cell death. Both toxins increased reactive oxygen species (ROS), with greater levels under co-exposure, while LPO was mainly elevated by individual treatments. Combined exposure led to cell cycle arrest, characterized by SubG1 accumulation and reduction in S and M phases. Apoptosis and necrosis varied with time and dose, with co-exposure favoring late apoptosis and necrosis. These results demonstrate that BEA and PAT act an enhanced manner through oxidative and cell cycle–related mechanisms, underscoring the importance of considering co-exposures in neurotoxicity risk assessment.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104860"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145404580","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 : 2025-12-01Epub Date: 2025-10-31DOI: 10.1016/j.etap.2025.104861
Tuğba Tezcan , Selin Özkan-Kotiloğlu , Mukaddes Asena Yıldırım , Mustafa Danışman , H. Ceren Bozmaoğlu , Kenan Can Tok , İrem Kar , Mehmet Gümüştaş , İnci Özgür-İlhan , Halit Sinan Süzen , Dilek Kaya-Akyüzlü
This study investigated whether hsa-miR-29a-3p expression affects diazepam (DZP) metabolism by modulating CYP2C19 gene expression in patients with alcohol withdrawal syndrome (AWS). Blood samples were obtained from 75 male AWS patients. hsa-miR-29a-3p expression was quantified using qRT-PCR, and plasma DZP and its active metabolite nordiazepam (NDZP) levels were measured via HPLC. No significant correlations were found between hsa-miR-29a-3p expression and DZP dose, plasma DZP/NDZP levels, dose-adjusted or weight-adjusted concentrations, or the metabolite-to-parent drug ratio. However, hsa-miR-29a-3p expression levels were significantly higher in patients exhibiting confusion (p = 0.016) and excessive fatigue (p = 0.039). Although hsa-miR-29a-3p did not appear to influence diazepam biotransformation directly, this study is the first to report a potential link between elevated hsa-miR-29a-3p expression and neuropsychiatric symptoms in AWS, suggesting a possible role of this microRNA in the clinical presentation of alcohol withdrawal.
{"title":"Evaluation of hsa-miR-29a-3p expression and diazepam biotransformation via CYP2C19 in alcohol withdrawal syndrome","authors":"Tuğba Tezcan , Selin Özkan-Kotiloğlu , Mukaddes Asena Yıldırım , Mustafa Danışman , H. Ceren Bozmaoğlu , Kenan Can Tok , İrem Kar , Mehmet Gümüştaş , İnci Özgür-İlhan , Halit Sinan Süzen , Dilek Kaya-Akyüzlü","doi":"10.1016/j.etap.2025.104861","DOIUrl":"10.1016/j.etap.2025.104861","url":null,"abstract":"<div><div>This study investigated whether <em>hsa-miR-29a-3p</em> expression affects diazepam (DZP) metabolism by modulating <em>CYP2C19</em> gene expression in patients with alcohol withdrawal syndrome (AWS). Blood samples were obtained from 75 male AWS patients. <em>hsa-miR-29a-3p</em> expression was quantified using qRT-PCR, and plasma DZP and its active metabolite nordiazepam (NDZP) levels were measured via HPLC. No significant correlations were found between <em>hsa-miR-29a-3p</em> expression and DZP dose, plasma DZP/NDZP levels, dose-adjusted or weight-adjusted concentrations, or the metabolite-to-parent drug ratio. However, <em>hsa-miR-29a-3p</em> expression levels were significantly higher in patients exhibiting confusion (p = 0.016) and excessive fatigue (p = 0.039). Although <em>hsa-miR-29a-3p</em> did not appear to influence diazepam biotransformation directly, this study is the first to report a potential link between elevated <em>hsa-miR-29a-3p</em> expression and neuropsychiatric symptoms in AWS, suggesting a possible role of this microRNA in the clinical presentation of alcohol withdrawal.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104861"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145405035","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 : 2025-12-01Epub Date: 2025-11-10DOI: 10.1016/j.etap.2025.104853
Alessandro Giammona , Clarissa Gervasoni , Gianluca Di Iulio , Carmina Sirignano , Stefano Listrani , Matteo Rinaldi , Silvia Canepari , Alessia Lo Dico , Francesca Costabile , Gloria Bertoli
Adverse health effects associated with fine particulate matter (PM2.5) in urban areas can occur even at PM2.5 concentrations below current regulatory limits — a situation increasingly observed in high-income countries. However, the underlying biological mechanisms remain poorly understood. In this study, we investigated the molecular and cellular responses in human bronchial epithelial cells exposed to low PM2.5 using a novel methodology. We first identified specific meteorological conditions that favor low PM2.5 mass concentrations (10 g m−3) combined with high traffic-related aerosol emissions, which we found to correspond to a highly oxidant atmosphere. Under these conditions, PM2.5 samples were collected in the urban background of Rome. The cells were exposed in vitro using a novel methodological approach based on a direct filter-contact model. Our focus was on associating measurable aerosol properties with gene expression pathways related to oxidative stress, inflammation, and their epigenetic modulation through microRNAs. Our findings indicate that exposure to fresh traffic-related aerosols under low PM2.5 concentrations elicited a biphasic gene expression response. The initial response involved the activation of genes such as NRF2, NF-B, CAT1, SOD1, HIF-1, and HMOX1; while a secondary response involved TNF- and GPX4. A strong association was observed between these biological effects and black carbon metrics related to fossil fuel, implicating fresh traffic emissions as key contributors. Additionally, a significant modulation of air pollution-associated microRNAs was observed, even at early times of exposure, suggesting an epigenetic dimension to the cellular stress response. These findings have important implications for future air quality regulations. We provide mechanistic insights into oxidative and epigenetic responses underlying PM2.5 induced biological effects at low PM2.5 levels, emphasizing that neither PM2.5 mass concentration nor its oxidative potential — two metrics currently considered by legislation — are sufficient on their own to explain the observed effects.
与城市地区细颗粒物（PM2.5）相关的不良健康影响，即使PM2.5浓度低于目前的监管限制，也会发生——这种情况在高收入国家越来越多地观察到。然而，潜在的生物学机制仍然知之甚少。在这项研究中，我们使用一种新颖的方法研究了暴露于低PM2.5的人支气管上皮细胞的分子和细胞反应。我们首先确定了有利于低PM2.5质量浓度（<10 μg m - 3）和高交通相关气溶胶排放的特定气象条件，我们发现这与高度氧化的大气相对应。在这些条件下，在罗马城市背景中采集PM2.5样本。使用基于直接过滤器-接触模型的新方法在体外暴露细胞。我们的重点是将可测量的气溶胶特性与氧化应激、炎症及其通过microrna进行表观遗传调节相关的基因表达途径联系起来。我们的研究结果表明，暴露于低PM2.5浓度下的新鲜交通相关气溶胶引发了双相基因表达反应。最初的反应涉及NRF2、NF-κB、CAT1、SOD1、HIF-1α和HMOX1等基因的激活；而继发性反应涉及TNF-α和GPX4。在这些生物效应和与化石燃料相关的黑碳指标之间观察到强烈的关联，这意味着新的交通排放是关键因素。此外，即使在暴露的早期，也观察到与空气污染相关的microrna的显著调节，这表明细胞应激反应的表观遗传维度。这些发现对未来的空气质量法规具有重要意义。我们提供了低PM2.5水平下PM2.5诱导的生物效应的氧化和表观遗传机制，强调PM2.5质量浓度及其氧化电位这两个目前被立法考虑的指标本身都不足以解释所观察到的效应。
{"title":"Cellular responses of human bronchial epithelial cells following short-term exposure to oxidative particulate matter","authors":"Alessandro Giammona , Clarissa Gervasoni , Gianluca Di Iulio , Carmina Sirignano , Stefano Listrani , Matteo Rinaldi , Silvia Canepari , Alessia Lo Dico , Francesca Costabile , Gloria Bertoli","doi":"10.1016/j.etap.2025.104853","DOIUrl":"10.1016/j.etap.2025.104853","url":null,"abstract":"<div><div>Adverse health effects associated with fine particulate matter (PM<sub>2.5</sub>) in urban areas can occur even at PM<sub>2.5</sub> concentrations below current regulatory limits — a situation increasingly observed in high-income countries. However, the underlying biological mechanisms remain poorly understood. In this study, we investigated the molecular and cellular responses in human bronchial epithelial cells exposed to low PM<sub>2.5</sub> using a novel methodology. We first identified specific meteorological conditions that favor low PM<sub>2.5</sub> mass concentrations (<span><math><mo><</mo></math></span>10 <span><math><mi>μ</mi></math></span>g m<sup>−3</sup>) combined with high traffic-related aerosol emissions, which we found to correspond to a highly oxidant atmosphere. Under these conditions, PM<sub>2.5</sub> samples were collected in the urban background of Rome. The cells were exposed <em>in vitro</em> using a novel methodological approach based on a direct filter-contact model. Our focus was on associating measurable aerosol properties with gene expression pathways related to oxidative stress, inflammation, and their epigenetic modulation through microRNAs. Our findings indicate that exposure to fresh traffic-related aerosols under low PM<sub>2.5</sub> concentrations elicited a biphasic gene expression response. The initial response involved the activation of genes such as <em>NRF2</em>, <em>NF-</em><span><math><mi>κ</mi></math></span><em>B</em>, <em>CAT1</em>, <em>SOD1</em>, <em>HIF-1</em><span><math><mi>α</mi></math></span>, and <em>HMOX1</em>; while a secondary response involved <em>TNF-</em><span><math><mi>α</mi></math></span> and <em>GPX4</em>. A strong association was observed between these biological effects and black carbon metrics related to fossil fuel, implicating fresh traffic emissions as key contributors. Additionally, a significant modulation of air pollution-associated microRNAs was observed, even at early times of exposure, suggesting an epigenetic dimension to the cellular stress response. These findings have important implications for future air quality regulations. We provide mechanistic insights into oxidative and epigenetic responses underlying PM<sub>2.5</sub> induced biological effects at low PM<sub>2.5</sub> levels, emphasizing that neither PM<sub>2.5</sub> mass concentration nor its oxidative potential — two metrics currently considered by legislation — are sufficient on their own to explain the observed effects.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104853"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145485027","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}
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