Pub Date : 2025-11-01DOI: 10.1016/j.fct.2025.115826
Lynn A. Abdallah , Areej Merhi , Nathalie Hayeck , Houssam Shaib , Mohamad G. Abiad , Omar Obeid , Christelle F. Iskandar
Pyrrolizidine alkaloids (PAs) are phytotoxins that can contaminate Camellia sinensis, posing health risks through tea consumption. This study aimed to quantify six PAs in 32 loose tea samples (17 black, 15 green) available in the Lebanese market and collected from Beirut suburbs using UPLC-MS/MS, compare with EU guidelines, and assess dietary exposure risks. The results showed sum PA concentrations averaged 110.4 μg/kg (range 12.2–609.9 μg/kg), with black teas showing higher average contamination (125.9 μg/kg) than green teas (92.9 μg/kg) (P > 0.05).Exposure assessments revealed samples exceeding the EU PA limits for both adults and children. Long-term MOE risk assessments indicated minimal risk for adults, but moderate concern for children, particularly with frequent consumption. These findings underscore the need for stricter regulations and enhanced monitoring to mitigate dietary PA exposure risks.
{"title":"Pyrrolizidine alkaloid contamination in loose tea and its health risk assessment","authors":"Lynn A. Abdallah , Areej Merhi , Nathalie Hayeck , Houssam Shaib , Mohamad G. Abiad , Omar Obeid , Christelle F. Iskandar","doi":"10.1016/j.fct.2025.115826","DOIUrl":"10.1016/j.fct.2025.115826","url":null,"abstract":"<div><div>Pyrrolizidine alkaloids (PAs) are phytotoxins that can contaminate <em>Camellia sinensis</em>, posing health risks through tea consumption. This study aimed to quantify six PAs in 32 loose tea samples (17 black, 15 green) available in the Lebanese market and collected from Beirut suburbs using UPLC-MS/MS, compare with EU guidelines, and assess dietary exposure risks. The results showed sum PA concentrations averaged 110.4 μg/kg (range 12.2–609.9 μg/kg), with black teas showing higher average contamination (125.9 μg/kg) than green teas (92.9 μg/kg) (P > 0.05).Exposure assessments revealed samples exceeding the EU PA limits for both adults and children. Long-term MOE risk assessments indicated minimal risk for adults, but moderate concern for children, particularly with frequent consumption. These findings underscore the need for stricter regulations and enhanced monitoring to mitigate dietary PA exposure risks.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115826"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-07-30DOI: 10.1016/j.fct.2025.115674
Siyanda Mazaleni, Anil A Chuturgoon, Terisha Ghazi
Deoxynivalenol (DON) is a globally distributed mycotoxin that contaminates agricultural foods. Previous studies have reported high concentrations of DON in staple foods as well as its associated toxic effects; however, there are limited studies on DNA methylation. Therefore, we investigated the effect of DON on global DNA methylation as well as the possible mechanism of DNA methylation changes by miR-29b and DNA methylation regulators in human hepatocellular carcinoma (HepG2) cells. HepG2 cells were exposed to 5, 10, and 26.17 μM of DON for 72 h. Global DNA methylation was determined using ELISA, whilst DNMT1, DNMT3a, DNMT3b, MBD2, TET1-3, and miR-29b expressions were measured using qPCR. The protein expression of DNMT1, DNMT3a, DNMT3b, and MBD2 was determined by Western blotting. At concentrations of 10 and 26.17 μM, DON induced global DNA hypomethylation. DON upregulated DNMT1 and downregulated DNMT3b; however, DNMT3a was only significantly downregulated by 5 μM DON. The protein expression of DNMT1 was upregulated and DNMT3b was downregulated at all DON concentrations, whereas DNMT3a was downregulated by 10 and 26.17 μM DON. DON upregulated MBD2 mRNA expression but downregulated its protein expression. TET2 and TET3 were upregulated, while TET1 was downregulated. miR-29b expression was significantly upregulated by 10 and 26.17 μM DON. Together, these results indicate that DON induced global DNA hypomethylation in HepG2 cells by altering miR-29b expression as well as DNMTs, MBD2, and TET expression levels, and provide insight into the potential of DON, as a DNA hypomethylation inducer, to cause genomic instability and cancer initiation and progression.
{"title":"Deoxynivalenol induces global DNA hypomethylation by modulating the expression of miR-29b and DNA methylation regulators in HepG2 cells.","authors":"Siyanda Mazaleni, Anil A Chuturgoon, Terisha Ghazi","doi":"10.1016/j.fct.2025.115674","DOIUrl":"10.1016/j.fct.2025.115674","url":null,"abstract":"<p><p>Deoxynivalenol (DON) is a globally distributed mycotoxin that contaminates agricultural foods. Previous studies have reported high concentrations of DON in staple foods as well as its associated toxic effects; however, there are limited studies on DNA methylation. Therefore, we investigated the effect of DON on global DNA methylation as well as the possible mechanism of DNA methylation changes by miR-29b and DNA methylation regulators in human hepatocellular carcinoma (HepG2) cells. HepG2 cells were exposed to 5, 10, and 26.17 μM of DON for 72 h. Global DNA methylation was determined using ELISA, whilst DNMT1, DNMT3a, DNMT3b, MBD2, TET1-3, and miR-29b expressions were measured using qPCR. The protein expression of DNMT1, DNMT3a, DNMT3b, and MBD2 was determined by Western blotting. At concentrations of 10 and 26.17 μM, DON induced global DNA hypomethylation. DON upregulated DNMT1 and downregulated DNMT3b; however, DNMT3a was only significantly downregulated by 5 μM DON. The protein expression of DNMT1 was upregulated and DNMT3b was downregulated at all DON concentrations, whereas DNMT3a was downregulated by 10 and 26.17 μM DON. DON upregulated MBD2 mRNA expression but downregulated its protein expression. TET2 and TET3 were upregulated, while TET1 was downregulated. miR-29b expression was significantly upregulated by 10 and 26.17 μM DON. Together, these results indicate that DON induced global DNA hypomethylation in HepG2 cells by altering miR-29b expression as well as DNMTs, MBD2, and TET expression levels, and provide insight into the potential of DON, as a DNA hypomethylation inducer, to cause genomic instability and cancer initiation and progression.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115674"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.fct.2025.115681
Iñaki Lacomba, Antonio López, Raquel Hervàs-Ayala, Clara Coscollà
Prenatal exposure to persistent organic pollutants (POPs) is a matter of great concern due to the vulnerability of the foetus. Seventeen polychlorinated dibenzo-p-dioxins and dibenzofurans (PCCD/Fs) and 12 dioxin-like polychlorinated biphenyls (dl-PCBs) were measured in meconium samples from 50 Spanish newborns using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Median concentrations (wet weight) of PCDD/Fs and dl-PCBs were 0.017 pg toxic equivalents (TEQ)/g and 0.0017 pg TEQ/g, respectively. Highly significant correlations were observed between some congeners of dl-PCBs and octachlorodibenzo-p-dioxin (OCDD), suggesting their similar sources and kinetic behaviour. Neonatal weight and gestational age were demographic parameters that influenced dl-PCB levels in meconium. Multiple regression analysis showed that consumption of ultra-processed foods contributed to the levels of several dl-PCBs in meconium. Our study concludes that meconium may be employed as a human matrix for assessing prenatal exposure to POPs and provides, for the first time, information about predictors of exposure and biomonitoring of dioxins and furans in biological meconium samples.
{"title":"Biomonitoring and exposure predictors of 29 dioxin, furan, and dl-PCB congeners in newborn meconium from Spain.","authors":"Iñaki Lacomba, Antonio López, Raquel Hervàs-Ayala, Clara Coscollà","doi":"10.1016/j.fct.2025.115681","DOIUrl":"10.1016/j.fct.2025.115681","url":null,"abstract":"<p><p>Prenatal exposure to persistent organic pollutants (POPs) is a matter of great concern due to the vulnerability of the foetus. Seventeen polychlorinated dibenzo-p-dioxins and dibenzofurans (PCCD/Fs) and 12 dioxin-like polychlorinated biphenyls (dl-PCBs) were measured in meconium samples from 50 Spanish newborns using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Median concentrations (wet weight) of PCDD/Fs and dl-PCBs were 0.017 pg toxic equivalents (TEQ)/g and 0.0017 pg TEQ/g, respectively. Highly significant correlations were observed between some congeners of dl-PCBs and octachlorodibenzo-p-dioxin (OCDD), suggesting their similar sources and kinetic behaviour. Neonatal weight and gestational age were demographic parameters that influenced dl-PCB levels in meconium. Multiple regression analysis showed that consumption of ultra-processed foods contributed to the levels of several dl-PCBs in meconium. Our study concludes that meconium may be employed as a human matrix for assessing prenatal exposure to POPs and provides, for the first time, information about predictors of exposure and biomonitoring of dioxins and furans in biological meconium samples.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115681"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.fct.2025.115827
Xingyuan Li , Hui Li
Bisphenol A (BPA)—a prevalent environmental contaminant commonly found in plastics—has potential adverse effects on human health. Despite its widespread use, the toxicological mechanisms of BPA in gynecological cancers remain unclear. This study aimed to investigate the potential role of BPA in cervical, endometrial, and ovarian cancers using network toxicology, molecular docking, and molecular dynamics simulations. We identified 683 potential targets of BPA, as well as 496, 207, and 344 overlapping genes associated with cervical, endometrial, and ovarian cancers, respectively. The key genes CXCL8 and MMP9 were consistently upregulated in all three cancers. Molecular docking analysis revealed significant binding affinities of BPA to CXCL8 (˗6.5 kcal/mol) and MMP9 (˗8.5 kcal/mol). Molecular dynamics simulations further confirmed the stability of these interactions, indicating that BPA may promote the development and progression of gynecological tumors through these targets. The regulation of MMP9, CXCL8, TNF, ESR1, UBA52, and PTGS2 expression by BPA was also demonstrated by RT-PCR and Western blot assays. In addition, the effects of MMP9 and CXCL8 on the migration of female reproductive cancer cells were successfully validated by Transwell. This study highlights the utility of network toxicology in understanding the mechanisms of environmental pollutants and emphasizes the need for further investigations into the effects of BPA exposure.
{"title":"Assessing the role of bisphenol A in female reproductive cancers using network toxicology, molecular dynamics, and preliminary experimental validation","authors":"Xingyuan Li , Hui Li","doi":"10.1016/j.fct.2025.115827","DOIUrl":"10.1016/j.fct.2025.115827","url":null,"abstract":"<div><div>Bisphenol A (BPA)—a prevalent environmental contaminant commonly found in plastics—has potential adverse effects on human health. Despite its widespread use, the toxicological mechanisms of BPA in gynecological cancers remain unclear. This study aimed to investigate the potential role of BPA in cervical, endometrial, and ovarian cancers using network toxicology, molecular docking, and molecular dynamics simulations. We identified 683 potential targets of BPA, as well as 496, 207, and 344 overlapping genes associated with cervical, endometrial, and ovarian cancers, respectively. The key genes CXCL8 and MMP9 were consistently upregulated in all three cancers. Molecular docking analysis revealed significant binding affinities of BPA to CXCL8 (˗6.5 kcal/mol) and MMP9 (˗8.5 kcal/mol). Molecular dynamics simulations further confirmed the stability of these interactions, indicating that BPA may promote the development and progression of gynecological tumors through these targets. The regulation of MMP9, CXCL8, TNF, ESR1, UBA52, and PTGS2 expression by BPA was also demonstrated by RT-PCR and Western blot assays. In addition, the effects of MMP9 and CXCL8 on the migration of female reproductive cancer cells were successfully validated by Transwell. This study highlights the utility of network toxicology in understanding the mechanisms of environmental pollutants and emphasizes the need for further investigations into the effects of BPA exposure.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115827"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.fct.2025.115825
Yağmur Özhan , Etil Güzelmeric , Zeynep Çokçeken , Rengin Reis , Muhammed Hamitoğlu , Gulcin Tugcu , Yüksel Kan , Ahmet Aydın , Hande Sipahi
Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic agents for the management of mild to moderate pain. Though clinically safe at therapeutic doses, excessive use causes severe toxicity due to reactive metabolites inducing oxidative stress and hepatotoxicity. Sideritis congesta, has been traditionally utilized for its anti-inflammatory, anti-ulcer, antioxidant, and antimicrobial properties. In the present study, we aimed to investigate the potential protective effects of S. congesta aqueous and hydroalcoholic extract against APAP-induced cytotoxicity and oxidative stress in HepG2 cell line. The anti-inflammatory and anti-mutagenic activities of S. congesta AE has been evaluated. Moreover, bioactive compounds were further analyzed using in silico methodologies to predict biological activities. Our findings revealed that APAP treatment significantly reduced SOD and CAT activity along with GSH level, whereas pretreatment with S.congesta extracts effectively restored their activities. Additionally, APAP-induced elevated MDA levels, was significantly mitigated by S. congesta extracts. Moreover, its extracts demonstrated potent antimutagenic activity. These findings show that S. congesta has strong hepatoprotective effects against APAP-induced oxidative stress and cytotoxicity. Its ability to modulate antioxidant defense systems, inhibit lipid peroxidation, and exert anti-inflammatory and anti-mutagenic effects underscores its potential as a natural therapeutic candidate for mitigating APAP-induced toxicity.
{"title":"Exploring the cytoprotective potential of Sideritis congesta extracts in APAP-induced hepatotoxicity: in vitro and in silico approaches","authors":"Yağmur Özhan , Etil Güzelmeric , Zeynep Çokçeken , Rengin Reis , Muhammed Hamitoğlu , Gulcin Tugcu , Yüksel Kan , Ahmet Aydın , Hande Sipahi","doi":"10.1016/j.fct.2025.115825","DOIUrl":"10.1016/j.fct.2025.115825","url":null,"abstract":"<div><div>Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic agents for the management of mild to moderate pain. Though clinically safe at therapeutic doses, excessive use causes severe toxicity due to reactive metabolites inducing oxidative stress and hepatotoxicity. <em>Sideritis congesta,</em> has been traditionally utilized for its anti-inflammatory, anti-ulcer, antioxidant, and antimicrobial properties. In the present study, we aimed to investigate the potential protective effects of <em>S. congesta</em> aqueous and hydroalcoholic extract against APAP-induced cytotoxicity and oxidative stress in HepG2 cell line. The anti-inflammatory and anti-mutagenic activities of <em>S. congesta</em> AE has been evaluated. Moreover, bioactive compounds were further analyzed using <em>in silico</em> methodologies to predict biological activities. Our findings revealed that APAP treatment significantly reduced SOD and CAT activity along with GSH level, whereas pretreatment with <em>S.congesta</em> extracts effectively restored their activities. Additionally, APAP-induced elevated MDA levels, was significantly mitigated by <em>S. congesta</em> extracts. Moreover, its extracts demonstrated potent antimutagenic activity. These findings show that <em>S. congesta</em> has strong hepatoprotective effects against APAP-induced oxidative stress and cytotoxicity. Its ability to modulate antioxidant defense systems, inhibit lipid peroxidation, and exert anti-inflammatory and anti-mutagenic effects underscores its potential as a natural therapeutic candidate for mitigating APAP-induced toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115825"},"PeriodicalIF":3.5,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.fct.2025.115824
Peipei Wu , Danqi Chen , Fei Wang , Kun Lu , Einar M. Sigurdsson , Chunyuan Jin
{"title":"Corrigendum to “Formaldehyde induces and promotes Alzheimer's disease pathologies in a 3D human neural cell culture model” [Food Chem. Toxicol. (2025 Dec) 206 115777]","authors":"Peipei Wu , Danqi Chen , Fei Wang , Kun Lu , Einar M. Sigurdsson , Chunyuan Jin","doi":"10.1016/j.fct.2025.115824","DOIUrl":"10.1016/j.fct.2025.115824","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115824"},"PeriodicalIF":3.5,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.fct.2025.115814
Yuyang Yao , Juer Liu , Yanling Cheng , Qiming Miao , Xinyue Zhu , Jingyi Xie , Na Zhang , Wei Hua , Guangwei Huang , Xiangyang Lin , Shengquan Mi , Roger Ruan
Almond hulls (AH) are a by-product of almond production, contain bioactive compounds with potential health benefits. This study evaluated the subchronic toxicity of AH in a 90-day oral toxicity study following OECD Guideline 408. Sprague-Dawley rats (96 total, 48 per sex) were assigned into four groups and fed diets containing AH at concentrations of 0 %, 0.625 %, 1.25 %, and 2.5 %, equivalent to doses of 0, 500, 1000, and 2000 mg/kg body weight/day. Rats were observed daily for clinical signs, with body weight and food consumption were recorded weekly. At the end of the study, hematology, clinical biochemistry, organ weights, and histopathology were assessed. No treatment-related adverse effects were observed in any group, including no changes in clinical signs, body weight, food consumption, or motor activity. Hematology and biochemical parameters were within normal ranges, and histopathology showed no abnormalities. The no-observed-adverse-effect level (NOAEL) for AH was determined to be 2.5 %, the highest dose tested, equivalent to 2000 mg/kg body weight/day. These findings confirm the safety of AH as a functional food ingredient. Combined with previous evidence showing no genotoxicity at doses up to 5000 mg/kg, AH is considered safe for human consumption at levels exceeding 322.58 mg/kg/day based on body weight.
{"title":"Lack of adverse effects in a subchronic 90-day oral toxicity study of almond hull powder in Sprague-Dawley rats","authors":"Yuyang Yao , Juer Liu , Yanling Cheng , Qiming Miao , Xinyue Zhu , Jingyi Xie , Na Zhang , Wei Hua , Guangwei Huang , Xiangyang Lin , Shengquan Mi , Roger Ruan","doi":"10.1016/j.fct.2025.115814","DOIUrl":"10.1016/j.fct.2025.115814","url":null,"abstract":"<div><div>Almond hulls (AH) are a by-product of almond production, contain bioactive compounds with potential health benefits. This study evaluated the subchronic toxicity of AH in a 90-day oral toxicity study following OECD Guideline 408. Sprague-Dawley rats (96 total, 48 per sex) were assigned into four groups and fed diets containing AH at concentrations of 0 %, 0.625 %, 1.25 %, and 2.5 %, equivalent to doses of 0, 500, 1000, and 2000 mg/kg body weight/day. Rats were observed daily for clinical signs, with body weight and food consumption were recorded weekly. At the end of the study, hematology, clinical biochemistry, organ weights, and histopathology were assessed. No treatment-related adverse effects were observed in any group, including no changes in clinical signs, body weight, food consumption, or motor activity. Hematology and biochemical parameters were within normal ranges, and histopathology showed no abnormalities. The no-observed-adverse-effect level (NOAEL) for AH was determined to be 2.5 %, the highest dose tested, equivalent to 2000 mg/kg body weight/day. These findings confirm the safety of AH as a functional food ingredient. Combined with previous evidence showing no genotoxicity at doses up to 5000 mg/kg, AH is considered safe for human consumption at levels exceeding 322.58 mg/kg/day based on body weight.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115814"},"PeriodicalIF":3.5,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by α-synuclein accumulation and mitochondrial impairment. Mitigating α-synuclein aggregation and mitochondrial dysfunction are prominent strategies in PD treatment. Apigenin, a dietary flavonoid, exhibits anti-inflammatory neuroprotective potential in PD models. However, it is still unclear whether apigenin possesses any impact on α-synuclein aggregation and mitochondrial dysfunction. Here, the effects and underlying mechanism of apigenin were investigated using MPP+-induced PD-like pathology in SH-SY5Y cells. Our results showed that apigenin significantly ameliorated neuronal apoptosis through inhibiting Bax/caspase-3 pathway and activating Bcl-2, increased size of SH-SY5Y neurospheres, and attenuated the levels of α-synuclein oligomers in MPP+-treated cells. Furthermore, apigenin improved MPP+-induced neurite damage as indicated by increased neurite length and expression of tyrosine hydroxylase (TH), growth associated protein 43 (GAP-43) and post-synaptic density protein (PSD-95). Increased ROS levels, depleted ATP levels, and decreased mitochondrial membrane potential and p-Drp1 expression in MPP+-treated cells were alleviated by apigenin. Further studies revealed that apigenin could enhance Akt activity. By using a specific Akt inhibitor, perifosine, the effects of apigenin on preventing MPP+-triggered PD pathologies were eliminated. Together, this work demonstrated that apigenin exerted neuroprotection by mitigating α-synuclein oligomers, neurite damage, mitochondrial dysfunction and neuronal apoptosis via Akt-dependent mechanism.
{"title":"MPP+ induces α-synuclein oligomerization and neurite impairment by disrupting mitochondrial function and Akt signaling, with apigenin emerging as a potential neuroprotective agent","authors":"Ratchaneekorn Reudhabibadh , Nidanut Champoochana , Zulkiflee Kuedo , Peungchaleoy Thammanichanon , Pilaiwanwadee Hutamekalin , Thunwa Binlateh","doi":"10.1016/j.fct.2025.115821","DOIUrl":"10.1016/j.fct.2025.115821","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by α-synuclein accumulation and mitochondrial impairment. Mitigating α-synuclein aggregation and mitochondrial dysfunction are prominent strategies in PD treatment. Apigenin, a dietary flavonoid, exhibits anti-inflammatory neuroprotective potential in PD models. However, it is still unclear whether apigenin possesses any impact on α-synuclein aggregation and mitochondrial dysfunction. Here, the effects and underlying mechanism of apigenin were investigated using MPP<sup>+</sup>-induced PD-like pathology in SH-SY5Y cells. Our results showed that apigenin significantly ameliorated neuronal apoptosis through inhibiting Bax/caspase-3 pathway and activating Bcl-2, increased size of SH-SY5Y neurospheres, and attenuated the levels of α-synuclein oligomers in MPP<sup>+</sup>-treated cells. Furthermore, apigenin improved MPP<sup>+</sup>-induced neurite damage as indicated by increased neurite length and expression of tyrosine hydroxylase (TH), growth associated protein 43 (GAP-43) and post-synaptic density protein (PSD-95). Increased ROS levels, depleted ATP levels, and decreased mitochondrial membrane potential and p-Drp1 expression in MPP<sup>+</sup>-treated cells were alleviated by apigenin. Further studies revealed that apigenin could enhance Akt activity. By using a specific Akt inhibitor, perifosine, the effects of apigenin on preventing MPP<sup>+</sup>-triggered PD pathologies were eliminated. Together, this work demonstrated that apigenin exerted neuroprotection by mitigating α-synuclein oligomers, neurite damage, mitochondrial dysfunction and neuronal apoptosis via Akt-dependent mechanism.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115821"},"PeriodicalIF":3.5,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27DOI: 10.1016/j.fct.2025.115822
Keith Morris-Schaffer , Sarah Dahlberg , Esther Johann , Mary M. Murphy , Nga L. Tran , Elaine L. Freeman
Sodium l-methylfolate (L-5-MTHF-Na; CAS Number 151533-22-1) is a source of folate proposed to be used as an alternative source of folic acid in human food. The safety of L-5-MTHF-Na was evaluated by testing for genotoxicity, and repeated dose toxicity in guideline preclinical studies. L-5-MTHF-Na was not mutagenic in the bacterial reverse mutation assay and did not induce cytogenetic effects in an in vitro chromosome aberration test and in vitro micronucleus test. In repeated dose 14-day and 90-day oral toxicity studies, rats administered up to 1000 mg/kg bw/day of L-5-MTHF-Na via oral gavage had no adverse treatment-related effects on any endpoint: clinical observations, body weights, food consumption, ophthalmic examination, neurological battery, hematology, clinical chemistry, urinalysis, tissue weights, macroscopic and microscopic observations. There was an observation of non-adverse adaptive changes in creatine kinase levels in male and female rats in the 90-day study with no tissue weight or histopathological correlate. The lack of adverse findings observed with L-5-MTHF-Na are consistent with negative findings observed in published preclinical and clinical studies on calcium l-methylfolate (L-5-MTHF-Ca). In conclusion, L-5-MTHF-Na is shown to have an overall safe profile for its use as a dietary source of folate for nutritional purposes.
l -甲基叶酸钠（L-5-MTHF-Na； CAS编号151533-22-1）是叶酸的一种来源，被提议用作人类食物中叶酸的替代来源。L-5-MTHF-Na的安全性在指导性临床前研究中通过遗传毒性试验和重复剂量毒性试验进行评估。L-5-MTHF-Na在细菌反向突变试验中不具有诱变性，在体外染色体畸变试验和体外微核试验中不诱导细胞遗传学效应。在14天和90天的重复剂量口服毒性研究中，大鼠通过灌胃给予高达1000 mg/kg体重/天的L-5-MTHF-Na，在临床观察、体重、食物消耗、眼科检查、神经电池、血液学、临床化学、尿液分析、组织重量、宏观和微观观察等任何终点都没有出现与治疗相关的不良影响。在90天的研究中，观察到雄性和雌性大鼠肌酸激酶水平的非不良适应性变化，没有组织重量或组织病理学相关。L-5-MTHF-Na没有观察到不良反应，这与已发表的l -甲基叶酸钙（L-5-MTHF-Ca）临床前和临床研究中观察到的不良反应一致。综上所述，L-5-MTHF-Na作为膳食叶酸的营养来源是安全的。
{"title":"Preclinical safety evaluation of sodium l-methylfolate","authors":"Keith Morris-Schaffer , Sarah Dahlberg , Esther Johann , Mary M. Murphy , Nga L. Tran , Elaine L. Freeman","doi":"10.1016/j.fct.2025.115822","DOIUrl":"10.1016/j.fct.2025.115822","url":null,"abstract":"<div><div>Sodium <span>l</span>-methylfolate (L-5-MTHF-Na; CAS Number 151533-22-1) is a source of folate proposed to be used as an alternative source of folic acid in human food. The safety of L-5-MTHF-Na was evaluated by testing for genotoxicity, and repeated dose toxicity in guideline preclinical studies. L-5-MTHF-Na was not mutagenic in the bacterial reverse mutation assay and did not induce cytogenetic effects in an <em>in vitro</em> chromosome aberration test and <em>in vitro</em> micronucleus test. In repeated dose 14-day and 90-day oral toxicity studies, rats administered up to 1000 mg/kg bw/day of L-5-MTHF-Na via oral gavage had no adverse treatment-related effects on any endpoint: clinical observations, body weights, food consumption, ophthalmic examination, neurological battery, hematology, clinical chemistry, urinalysis, tissue weights, macroscopic and microscopic observations. There was an observation of non-adverse adaptive changes in creatine kinase levels in male and female rats in the 90-day study with no tissue weight or histopathological correlate. The lack of adverse findings observed with L-5-MTHF-Na are consistent with negative findings observed in published preclinical and clinical studies on calcium <span>l</span>-methylfolate (L-5-MTHF-Ca). In conclusion, L-5-MTHF-Na is shown to have an overall safe profile for its use as a dietary source of folate for nutritional purposes.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115822"},"PeriodicalIF":3.5,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27DOI: 10.1016/j.fct.2025.115819
Se-Woong Park , In-Sik Shin , Sung-Hwan Kim , Han Na Suh
This study investigated the median lethal dose and target organs of polyhexamethylene guanidine phosphate (PHMG-P)—an antimicrobial disinfectant—administered via single-dose intravenous injection (IV; 3.13, 6.25, or 12.5 mg/kg) and intratracheal instillation (ITI; 2, 4, or 8 mg/kg) in Sprague-Dawley rats. Alterations in serum biochemical (blood urea nitrogen, creatinine, and gamma-glutamyl transferase), hematological (reticulocyte count), and hepatic histopathological features, such as tubular dilation and atypical morphology, indicated that nephrotoxicity was induced after the 12.5 mg/kg IV. Changes in lung weight, hematological (neutrophil), and histopathological parameters, including alveolar macrophage aggregation, bronchiolar epithelium de-/regeneration, and granulomatous inflammation/pulmonary fibrosis, indicated that lung damage was induced after 8 mg/kg ITI. The acute IV LD50 was 12.20 and 12.83 mg/kg in male and female rats, respectively, and the target organ was the kidney. In contrast, the acute ITI LD50 was 5.68 and 5.01 mg/kg in male and female rats, respectively, and the target organ was the lung. This study indicates that PHMG-P exerts varying toxic effects depending on the route of administration.
{"title":"Differential toxicity of polyhexamethylene guanidine phosphate administered through intravenous injection and intratracheal instillation in Sprague-Dawley rats","authors":"Se-Woong Park , In-Sik Shin , Sung-Hwan Kim , Han Na Suh","doi":"10.1016/j.fct.2025.115819","DOIUrl":"10.1016/j.fct.2025.115819","url":null,"abstract":"<div><div>This study investigated the median lethal dose and target organs of polyhexamethylene guanidine phosphate (PHMG-P)—an antimicrobial disinfectant—administered via single-dose intravenous injection (IV; 3.13, 6.25, or 12.5 mg/kg) and intratracheal instillation (ITI; 2, 4, or 8 mg/kg) in Sprague-Dawley rats. Alterations in serum biochemical (blood urea nitrogen, creatinine, and gamma-glutamyl transferase), hematological (reticulocyte count), and hepatic histopathological features, such as tubular dilation and atypical morphology, indicated that nephrotoxicity was induced after the 12.5 mg/kg IV. Changes in lung weight, hematological (neutrophil), and histopathological parameters, including alveolar macrophage aggregation, bronchiolar epithelium de-/regeneration, and granulomatous inflammation/pulmonary fibrosis, indicated that lung damage was induced after 8 mg/kg ITI. The acute IV LD<sub>50</sub> was 12.20 and 12.83 mg/kg in male and female rats, respectively, and the target organ was the kidney. In contrast, the acute ITI LD<sub>50</sub> was 5.68 and 5.01 mg/kg in male and female rats, respectively, and the target organ was the lung. This study indicates that PHMG-P exerts varying toxic effects depending on the route of administration.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115819"},"PeriodicalIF":3.5,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号