Pub Date : 2025-02-24DOI: 10.1016/j.fct.2025.115344
Mehrnoosh Abtahi , Mohammad Paeezi , Sina Dobaradaran , Azita Mohagheghian , Amin Bagheri , Reza Saeedi
The health risk and burden of disease associated with dietary exposure to pesticide residues in foodstuffs in Iran were assessed. The pesticide residue levels in foodstuffs in the country were determined through systematic review and meta-analysis. The non-carcinogenic risk, carcinogenic risk, and attributable burden of disease were estimated in terms of hazard quotient (HQ), incremental lifetime cancer risk (ILCR), and disability-adjusted life year (DALY), respectively. The meta-analysis showed that 58% of pesticide-food pairs lacked Codex maximum residue levels (MRLs), 34% had pesticide levels below these limits, and 8% exceeded them. Based on the average HQs, two foodstuffs (onion and tangerine) and two pesticides (haloxyfop-R-methyl and cyhalothrin) exhibited unacceptable non-cancer risk (>1.0). The average ILCR value of lindane was assessed to be at the unacceptable level (1.4 × 10−4). The total annual disease burden values attributable to pesticide residues in foodstuffs were assessed to be 242 for death cases, 0.29 for death rate (per 100,000 people), 13,792 for DALYs, and 16.1 for DALY rate. The three food items with the highest DALY rates from pesticide residues were cucumber (5.9), fish (3.9), and date (2.1). The health risk and disease burden of pesticide residues in foodstuffs were considered to be relatively high.
{"title":"Assessment of health risk and burden of disease associated with dietary exposure to pesticide residues through foodstuffs in Iran","authors":"Mehrnoosh Abtahi , Mohammad Paeezi , Sina Dobaradaran , Azita Mohagheghian , Amin Bagheri , Reza Saeedi","doi":"10.1016/j.fct.2025.115344","DOIUrl":"10.1016/j.fct.2025.115344","url":null,"abstract":"<div><div>The health risk and burden of disease associated with dietary exposure to pesticide residues in foodstuffs in Iran were assessed. The pesticide residue levels in foodstuffs in the country were determined through systematic review and meta-analysis. The non-carcinogenic risk, carcinogenic risk, and attributable burden of disease were estimated in terms of hazard quotient (HQ), incremental lifetime cancer risk (ILCR), and disability-adjusted life year (DALY), respectively. The meta-analysis showed that 58% of pesticide-food pairs lacked Codex maximum residue levels (MRLs), 34% had pesticide levels below these limits, and 8% exceeded them. Based on the average HQs, two foodstuffs (onion and tangerine) and two pesticides (haloxyfop-R-methyl and cyhalothrin) exhibited unacceptable non-cancer risk (>1.0). The average ILCR value of lindane was assessed to be at the unacceptable level (1.4 × 10<sup>−4</sup>). The total annual disease burden values attributable to pesticide residues in foodstuffs were assessed to be 242 for death cases, 0.29 for death rate (per 100,000 people), 13,792 for DALYs, and 16.1 for DALY rate. The three food items with the highest DALY rates from pesticide residues were cucumber (5.9), fish (3.9), and date (2.1). The health risk and disease burden of pesticide residues in foodstuffs were considered to be relatively high.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"199 ","pages":"Article 115344"},"PeriodicalIF":3.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511893","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 : 2025-02-22DOI: 10.1016/j.fct.2025.115335
Nan Wang , Zhengshan Gao , Honghong Zhan , Lin Jing , Fancheng Meng , Min Chen
Doxorubicin (DOX) is a potent anticancer drug, while its toxic side effects involve multi-organ toxicity, including hepatotoxicity. This study aims to investigate the therapeutic potential of salidroside against DOX-induced hepatotoxicity and elucidate its underlying mechanisms. Result showed that salidroside exhibited a liver protective effect in DOX-induced hepatotoxicity in mice, represented by the decreased serum ALT, AST and LDH levels, as well as the rescue of pathological changes in mice livers. Further study showed salidroside reduced the expression level of pyroptosis-associated proteins, including NLRP3, cleaved-caspase 1, gasdermin D (GSDMD-N) and mature IL-1β in mice liver tissues. In vitro study confirmed salidroside exerted a similar effect in AML12 cells. Mechanistically, salidroside alleviated mitochondrial dysfunction by activating the PGC-1α/Mfn2 signaling pathway, and restrained the endoplasmic reticulum (ER) stress, represented by the downregulation of GRP78 and p-PERK/PERK level. Subsequent investigations revealed that salidroside activated the Sestrin2/AMPK pathway, while the application of AMPK inhibitors, PGC-1α siRNA or Sestrain2 siRNA reversed the effects of salidroside on ameliorating mitochondrial dysfunction and ER stress, suggesting salidroside could be a promising therapeutic strategy for alleviating DOX-induced hepatotoxicity.
{"title":"Salidroside alleviates doxorubicin-induced hepatotoxicity via Sestrin2/AMPK-mediated pyroptotic inhibition","authors":"Nan Wang , Zhengshan Gao , Honghong Zhan , Lin Jing , Fancheng Meng , Min Chen","doi":"10.1016/j.fct.2025.115335","DOIUrl":"10.1016/j.fct.2025.115335","url":null,"abstract":"<div><div>Doxorubicin (DOX) is a potent anticancer drug, while its toxic side effects involve multi-organ toxicity, including hepatotoxicity. This study aims to investigate the therapeutic potential of salidroside against DOX-induced hepatotoxicity and elucidate its underlying mechanisms. Result showed that salidroside exhibited a liver protective effect in DOX-induced hepatotoxicity in mice, represented by the decreased serum ALT, AST and LDH levels, as well as the rescue of pathological changes in mice livers. Further study showed salidroside reduced the expression level of pyroptosis-associated proteins, including NLRP3, cleaved-caspase 1, gasdermin D (GSDMD-N) and mature IL-1β in mice liver tissues. In vitro study confirmed salidroside exerted a similar effect in AML12 cells. Mechanistically, salidroside alleviated mitochondrial dysfunction by activating the PGC-1α/Mfn2 signaling pathway, and restrained the endoplasmic reticulum (ER) stress, represented by the downregulation of GRP78 and p-PERK/PERK level. Subsequent investigations revealed that salidroside activated the Sestrin2/AMPK pathway, while the application of AMPK inhibitors, PGC-1α siRNA or Sestrain2 siRNA reversed the effects of salidroside on ameliorating mitochondrial dysfunction and ER stress, suggesting salidroside could be a promising therapeutic strategy for alleviating DOX-induced hepatotoxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"199 ","pages":"Article 115335"},"PeriodicalIF":3.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490103","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 : 2025-02-22DOI: 10.1016/j.fct.2025.115343
Aicha Mallouki , Yu-Syuan Luo
The prevalence and residue levels of mycotoxins in food have emerged as a global public health concern, exacerbated by climate change. Despite routine monitoring of mycotoxin residues in foodstuffs by health agencies, comprehensive exposure assessments remain limited due to insufficient food consumption data and complex food classification systems. This study employed the Stochastic Human Exposure and Dose Simulation High-Throughput (SHEDS-HT) model, adapted for the Taiwanese population with National Food Consumption Database (NFCD), to estimate aggregate dietary exposure to six major mycotoxins: aflatoxin B1, ochratoxin A, zearalenone, fumonisin B1, deoxynivalenol, and citrinin. Using Margin of Exposure (MoE) analysis, citrinin was identified as the non-carcinogenic priority mycotoxin, with infants and children being the most vulnerable group due to their higher intake of rice-based products per unit body weight. Additionally, 2.5% and 2.4% of the population exceeded the (provisional) tolerable daily intake (pTDI) for ochratoxin A and aflatoxin B1, respectively, with notable detection in candy, spices, sugar, and peanut-based products. For cancer risk characterization, aflatoxin B1 and ochratoxin A demonstrated MoE values below the critical safety threshold (10,000), indicating potential health risks. This study highlights the urgent need for coordinated surveillance and emphasizes the importance of biomonitoring approaches to better characterize total mycotoxin exposure in Taiwan, providing valuable insights for evidence-based risk management and regulatory strategies.
{"title":"Cancer- and non-cancer risk prioritization of regulated mycotoxins in Taiwan: Insights from the 2018–2022 official Mycotoxin monitoring survey","authors":"Aicha Mallouki , Yu-Syuan Luo","doi":"10.1016/j.fct.2025.115343","DOIUrl":"10.1016/j.fct.2025.115343","url":null,"abstract":"<div><div>The prevalence and residue levels of mycotoxins in food have emerged as a global public health concern, exacerbated by climate change. Despite routine monitoring of mycotoxin residues in foodstuffs by health agencies, comprehensive exposure assessments remain limited due to insufficient food consumption data and complex food classification systems. This study employed the Stochastic Human Exposure and Dose Simulation High-Throughput (SHEDS-HT) model, adapted for the Taiwanese population with National Food Consumption Database (NFCD), to estimate aggregate dietary exposure to six major mycotoxins: aflatoxin B1, ochratoxin A, zearalenone, fumonisin B1, deoxynivalenol, and citrinin. Using Margin of Exposure (MoE) analysis, citrinin was identified as the non-carcinogenic priority mycotoxin, with infants and children being the most vulnerable group due to their higher intake of rice-based products per unit body weight. Additionally, 2.5% and 2.4% of the population exceeded the (provisional) tolerable daily intake (pTDI) for ochratoxin A and aflatoxin B1, respectively, with notable detection in candy, spices, sugar, and peanut-based products. For cancer risk characterization, aflatoxin B1 and ochratoxin A demonstrated MoE values below the critical safety threshold (10,000), indicating potential health risks. This study highlights the urgent need for coordinated surveillance and emphasizes the importance of biomonitoring approaches to better characterize total mycotoxin exposure in Taiwan, providing valuable insights for evidence-based risk management and regulatory strategies.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"199 ","pages":"Article 115343"},"PeriodicalIF":3.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490171","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 : 2025-02-21DOI: 10.1016/j.fct.2025.115306
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, 3-phenylbutanal, CAS registry number 16251-77-7","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115306","DOIUrl":"10.1016/j.fct.2025.115306","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115306"},"PeriodicalIF":3.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476079","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 : 2025-02-21DOI: 10.1016/j.fct.2025.115341
Juman Alsaab , Wedad S. Sarawi , Ahlam M. Alhusaini , Iman H. Hasan , Sumayya Alturaif , Rehab A. Ali , Nouf M. Alrasheed , Raeesa Mohammad , Norah K. Algarzae
Methotrexate (MTX), a potent chemotherapeutic and immunosuppressive agent, is widely used for cancer and autoimmune diseases. MTX-induced hepatotoxicity is a well-recognized adverse response, even at relatively low doses. This study investigates the possible protective effects of procyanidin B2 (PCB2) on MTX-induced hepatotoxicity. Rats were orally treated with PCB2 (40 mg/kg) for 10 days, followed by a single intraperitoneal MTX injection (20 mg/kg) on day 8. The study also included a positive control group treated with quercetin (20 mg/kg), a known antioxidant, alongside MTX. The results revealed that MTX-induced hepatic injury was evidenced by elevation in serum transaminases. This elevation was accompanied by hepatic oxidative stress due to an imbalance in oxidative/antioxidant markers, specifically elevated malondialdehyde (MDA) and decreased glutathione (GSH) levels and superoxide dismutase (SOD) activity. The inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were markedly upregulated in the liver of MTX-intoxicated rats. Additionally, the expressions of nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), caspase-3 and gasdermin E (GSDME) were significantly increased in MTX rats. The use of PCB2 significantly ameliorated the deleterious effect of MTX on previous parameters by restoring oxidant/antioxidant balance, decreasing the inflammatory markers, and normalizing the expression of NF-κB, TLR4, caspase-3 and GSDME. In conclusion, this study uncovered the potential role of PCB2 on MTX-induced hepatotoxicity, confirming its antioxidant, anti-inflammatory, and anti-pyroptosis effects yet, further studies are needed to support its use as a protective therapy against such toxicity.
{"title":"Procyanidin B2 mitigates methotrexate-induced hepatic pyroptosis by suppressing TLR4/NF-κB and caspase-3/GSDME pathways","authors":"Juman Alsaab , Wedad S. Sarawi , Ahlam M. Alhusaini , Iman H. Hasan , Sumayya Alturaif , Rehab A. Ali , Nouf M. Alrasheed , Raeesa Mohammad , Norah K. Algarzae","doi":"10.1016/j.fct.2025.115341","DOIUrl":"10.1016/j.fct.2025.115341","url":null,"abstract":"<div><div>Methotrexate (MTX), a potent chemotherapeutic and immunosuppressive agent, is widely used for cancer and autoimmune diseases. MTX-induced hepatotoxicity is a well-recognized adverse response, even at relatively low doses. This study investigates the possible protective effects of procyanidin B2 (PCB2) on MTX-induced hepatotoxicity. Rats were orally treated with PCB2 (40 mg/kg) for 10 days, followed by a single intraperitoneal MTX injection (20 mg/kg) on day 8. The study also included a positive control group treated with quercetin (20 mg/kg), a known antioxidant, alongside MTX. The results revealed that MTX-induced hepatic injury was evidenced by elevation in serum transaminases. This elevation was accompanied by hepatic oxidative stress due to an imbalance in oxidative/antioxidant markers, specifically elevated malondialdehyde (MDA) and decreased glutathione (GSH) levels and superoxide dismutase (SOD) activity. The inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were markedly upregulated in the liver of MTX-intoxicated rats. Additionally, the expressions of nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), caspase-3 and gasdermin E (GSDME) were significantly increased in MTX rats. The use of PCB2 significantly ameliorated the deleterious effect of MTX on previous parameters by restoring oxidant/antioxidant balance, decreasing the inflammatory markers, and normalizing the expression of NF-κB, TLR4, caspase-3 and GSDME. In conclusion, this study uncovered the potential role of PCB2 on MTX-induced hepatotoxicity, confirming its antioxidant, anti-inflammatory, and anti-pyroptosis effects yet, further studies are needed to support its use as a protective therapy against such toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"199 ","pages":"Article 115341"},"PeriodicalIF":3.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479583","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 : 2025-02-20DOI: 10.1016/j.fct.2025.115342
Zhiming Ding , Hongzhen Ruan , Yujie Wang , Liuliu Dong , Caiyun Wu , Yunxia Cao , Huifen Xiang , Dan Liang
Fluorene-9-bisphenol (BHPF), a prevalent substitute for bisphenol A (BPA), has become a widespread endocrine disruptor found in numerous consumer products. Despite extensive research on its toxicological profile, the specific effects of BHPF on reproduction, particularly during early embryonic development, remain unclear. Therefore, in our study, we used an in vitro culture system of mouse embryos to treat fertilized eggs with different concentrations of BHPF, and applied immunofluorescence, cell live staining and transcriptome sequencing to explore the effects of BHPF on early embryonic development and related mechanisms. Our study demonstrates that BHPF exposure causes significant developmental arrest in early embryonic stages. Transcriptomic analysis revealed that BHPF exposure altered gene expression at the 2-cell stage, notably impairing zygotic genome activation and maternal mRNA degradation, which disrupted the maternal-to-zygotic transition. Furthermore, BHPF exposure impaired mitochondrial function, as illustrated by altered mitochondrial distribution, reduced membrane potential, and decreased ATP production. Oxidative stress and DNA damage in 2-cell embryos were linked to the accumulation of reactive oxygen species and superoxide anions induced by BHPF. Additionally, BHPF-treated embryos exhibited altered histone modification patterns, suggesting epigenetic disruptions. Overall, these results indicate that BHPF has the potential to disrupt early embryonic development, raising concerns regarding its safety as a BPA substitute.
芴-9-双酚（BHPF）是双酚 A（BPA）的普遍替代品，已成为广泛存在于众多消费品中的内分泌干扰物。尽管对其毒理学特征进行了广泛研究，但 BHPF 对生殖，尤其是早期胚胎发育的具体影响仍不清楚。因此，在我们的研究中，我们利用小鼠胚胎体外培养系统，用不同浓度的BHPF处理受精卵，并应用免疫荧光、细胞活体染色和转录组测序等方法来探讨BHPF对早期胚胎发育的影响及相关机制。我们的研究表明，暴露于BHPF会导致胚胎早期发育明显停滞。转录组分析表明，暴露于BHPF会改变2细胞期的基因表达，特别是影响子代基因组激活和母体mRNA降解，从而破坏母体向子代的转变。此外，暴露于 BHPF 会损害线粒体功能，表现为线粒体分布改变、膜电位降低和 ATP 生成减少。2细胞胚胎中的氧化应激和DNA损伤与BHPF诱导的活性氧和超氧阴离子的积累有关。此外，经 BHPF 处理的胚胎表现出组蛋白修饰模式的改变，表明存在表观遗传学破坏。总之，这些结果表明，BHPF 有可能破坏早期胚胎发育，从而引起人们对其作为双酚 A 替代品的安全性的担忧。
{"title":"BHPF inhibits early embryonic development in mice by disrupting maternal-to-zygotic transition and mitochondrial function","authors":"Zhiming Ding , Hongzhen Ruan , Yujie Wang , Liuliu Dong , Caiyun Wu , Yunxia Cao , Huifen Xiang , Dan Liang","doi":"10.1016/j.fct.2025.115342","DOIUrl":"10.1016/j.fct.2025.115342","url":null,"abstract":"<div><div>Fluorene-9-bisphenol (BHPF), a prevalent substitute for bisphenol A (BPA), has become a widespread endocrine disruptor found in numerous consumer products. Despite extensive research on its toxicological profile, the specific effects of BHPF on reproduction, particularly during early embryonic development, remain unclear. Therefore, in our study, we used an <em>in vitro</em> culture system of mouse embryos to treat fertilized eggs with different concentrations of BHPF, and applied immunofluorescence, cell live staining and transcriptome sequencing to explore the effects of BHPF on early embryonic development and related mechanisms. Our study demonstrates that BHPF exposure causes significant developmental arrest in early embryonic stages. Transcriptomic analysis revealed that BHPF exposure altered gene expression at the 2-cell stage, notably impairing zygotic genome activation and maternal mRNA degradation, which disrupted the maternal-to-zygotic transition. Furthermore, BHPF exposure impaired mitochondrial function, as illustrated by altered mitochondrial distribution, reduced membrane potential, and decreased ATP production. Oxidative stress and DNA damage in 2-cell embryos were linked to the accumulation of reactive oxygen species and superoxide anions induced by BHPF. Additionally, BHPF-treated embryos exhibited altered histone modification patterns, suggesting epigenetic disruptions. Overall, these results indicate that BHPF has the potential to disrupt early embryonic development, raising concerns regarding its safety as a BPA substitute.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"199 ","pages":"Article 115342"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476071","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 : 2025-02-20DOI: 10.1016/j.fct.2025.115339
Yuanyuan Li , Tingting Zhang , Qiaoxing Mou , Sirui Liu , Wanxing Wu , Simei Wang , Xiaoyu Yan , Jie Liang , Mengfan Yan , Weiying Liu , Xiaoqi Pan
Acrylamide (ACR) has garnered significant attention due to its neurotoxic effects. Oxidative stress, a key mechanism underlying ACR-induced neurotoxicity, is well-documented. Methionine sulfoxide reductase A (MsrA) plays a pivotal role in protecting various types of cells, including neuronal cells, against the effects of oxidative stress. However, the role of MsrA in ACR-induced neurotoxicity remains poorly understood. This study explored the effects of MsrA on ACR-induced neurotoxicity. After administering ACR by gavage at doses of 20 mg/kg, 30 mg/kg, and 40 mg/kg for 21 days, rats exhibited motor impairment and structural damage in the cerebellum. Both in vivo and in vitro, ACR dose-dependently reduced MsrA level, accompanied by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, c-Jun N-terminal kinase (JNK) phosphorylation, and mitochondria-dependent neuronal apoptosis. To further ascertain the role of MsrA in mitigating ACR-induced neuronal apoptosis, SH-SY5Y cell line overexpressing MsrA was constructed. Overexpression of MsrA attenuated the ACR-induced increases in ROS and MDA levels. Additionally, alterations in mitochondrial membrane potential (MMP), mitochondrial ultrastructure, JNK phosphorylation, and mitochondria-dependent apoptosis caused by ACR were reversed in the cells overexpressing MsrA. These findings offer significant insights into the protective role of MsrA against ACR-induced neurotoxicity.
{"title":"Overexpression of methionine sulfoxide reductase A alleviates acrylamide-induced neurotoxicity by mitigating lipid peroxidation and mitochondria-dependent apoptosis In vivo and In vitro","authors":"Yuanyuan Li , Tingting Zhang , Qiaoxing Mou , Sirui Liu , Wanxing Wu , Simei Wang , Xiaoyu Yan , Jie Liang , Mengfan Yan , Weiying Liu , Xiaoqi Pan","doi":"10.1016/j.fct.2025.115339","DOIUrl":"10.1016/j.fct.2025.115339","url":null,"abstract":"<div><div>Acrylamide (ACR) has garnered significant attention due to its neurotoxic effects. Oxidative stress, a key mechanism underlying ACR-induced neurotoxicity, is well-documented. Methionine sulfoxide reductase A (MsrA) plays a pivotal role in protecting various types of cells, including neuronal cells, against the effects of oxidative stress. However, the role of MsrA in ACR-induced neurotoxicity remains poorly understood. This study explored the effects of MsrA on ACR-induced neurotoxicity. After administering ACR by gavage at doses of 20 mg/kg, 30 mg/kg, and 40 mg/kg for 21 days, rats exhibited motor impairment and structural damage in the cerebellum. Both <em>in vivo</em> and <em>in vitro</em>, ACR dose-dependently reduced MsrA level, accompanied by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, c-Jun N-terminal kinase <strong>(</strong>JNK) phosphorylation, and mitochondria-dependent neuronal apoptosis. To further ascertain the role of MsrA in mitigating ACR-induced neuronal apoptosis, SH-SY5Y cell line overexpressing MsrA was constructed. Overexpression of MsrA attenuated the ACR-induced increases in ROS and MDA levels. Additionally, alterations in mitochondrial membrane potential (MMP), mitochondrial ultrastructure, JNK phosphorylation, and mitochondria-dependent apoptosis caused by ACR were reversed in the cells overexpressing MsrA. These findings offer significant insights into the protective role of MsrA against ACR-induced neurotoxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"199 ","pages":"Article 115339"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476075","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 : 2025-02-20DOI: 10.1016/j.fct.2025.115340
Caiyan Li , Zhuo Wang , Bingbing Song , Kit-Leong Cheung , Jianping Chen , Rui Li , Xiaofei Liu , Xuejing Jia , Qiaoli Zhao , Saiyi Zhong
Arsenolipid (AsL) is a complex lipid-soluble organic arsenic compound, which is usually found in marine organisms. Among them, arsenic-containing hydrocarbons (AsHCs) are a common type. At present, the toxic effects of different AsHCs have not been elucidated due to their different hydrocarbon chain lengths and large numbers. A model Caenorhabditis elegans (C.elegans) was used to study the reproductive toxicity and mechanism of AsHC 332, AsHC 346 and AsHC 360, which are commonly found in seafood. The results showed that three different molecular weights of AsLs reduced the number of offspring and gonadal area of C. elegans, prolonged the generation time. Meanwhile, the three AsLs regulated the expression levels of oxidative stress genes (isp-1, mev-1, sod-3, gas-1), resulting in changes in the expression of apoptosis-related genes (ced-3, ced-4, ced-9) and DNA damage-related genes (hus-1, clk-2, cep-1 and egl-1). In addition, the mechanism of arsenolipid-induced nematode reproductive toxicity was further elucidated through the HUS-1-CEP-1-EGL-1-CED-9-CED-4-CED-3 signaling pathway. Therefore, our results suggest that AsHC 332 is more exposed to reproductive toxicity than AsHC 346 and AsHC 360, which is related to changes in physicochemical properties and DNA damage-induced germ cell apoptosis.
{"title":"Arsenolipid-induced reproductive toxicity in Caenorhabditis elegans: Elucidating the mechanism through the HUS-1-CEP-1-EGL-1-CED-9-CED-4-CED-3 signaling pathway","authors":"Caiyan Li , Zhuo Wang , Bingbing Song , Kit-Leong Cheung , Jianping Chen , Rui Li , Xiaofei Liu , Xuejing Jia , Qiaoli Zhao , Saiyi Zhong","doi":"10.1016/j.fct.2025.115340","DOIUrl":"10.1016/j.fct.2025.115340","url":null,"abstract":"<div><div>Arsenolipid (AsL) is a complex lipid-soluble organic arsenic compound, which is usually found in marine organisms. Among them, arsenic-containing hydrocarbons (AsHCs) are a common type. At present, the toxic effects of different AsHCs have not been elucidated due to their different hydrocarbon chain lengths and large numbers. A model <em>Caenorhabditis elegans</em> (<em>C.elegans</em>) was used to study the reproductive toxicity and mechanism of AsHC 332, AsHC 346 and AsHC 360, which are commonly found in seafood. The results showed that three different molecular weights of AsLs reduced the number of offspring and gonadal area of <em>C. elegans</em>, prolonged the generation time. Meanwhile, the three AsLs regulated the expression levels of oxidative stress genes (<em>isp-1, mev-1, sod-3, gas-1</em>), resulting in changes in the expression of apoptosis-related genes (<em>ced-3, ced-4, ced-9</em>) and DNA damage-related genes (<em>hus-1, clk-2, cep-1 and egl-1</em>). In addition, the mechanism of arsenolipid-induced nematode reproductive toxicity was further elucidated through the HUS-1-CEP-1-EGL-1-CED-9-CED-4-CED-3 signaling pathway. Therefore, our results suggest that AsHC 332 is more exposed to reproductive toxicity than AsHC 346 and AsHC 360, which is related to changes in physicochemical properties and DNA damage-induced germ cell apoptosis.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115340"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476060","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 : 2025-02-19DOI: 10.1016/j.fct.2025.115334
Samyah T. Alanazi , Samir A. Salama , Musaad M. Althobaiti , Afnan Bakhsh , Najla M. Aljehani , Ebtisam Alanazi , Maha T. Alanazi , Arafa Musa
Cisplatin is a widely used chemotherapeutic agent. Nevertheless, a significant fraction of cisplatin-treated patients develops nephrotoxicity which limits cisplatin therapeutic implementation. The current work was devoted to investigate the potential nephroprotective impact of theaflavin against the cisplatin-induced nephrotoxicity using male Wistar rats as a mammalian model. The results indicated that theaflavin significantly improved the renal histopathological picture and glomerular filtration rate, along with reduced renal injury marker KIM-1, urinary albumin/creatinine ratio, serum creatinine, and urea. Mechanistically, theaflavin upregulated protein level of SIRT1 and downregulated the acetylated forms of the inflammatory transcription factor (TF) NF-kB, the antioxidant TF FOXO3a, and the pro-apoptotic TF p53 in the cisplatin-treated rats. Additionally, it upregulated the antioxidant TF Nrf2. In the same context, it suppressed the inflammatory responses, oxidative stress, and apoptosis. NF-kB nuclear translocation and levels of its responsive gene products IL-6 and TNF-α were suppressed. Lipids and DNA oxidation were reduced, and level of the antioxidant GSH and activity of the antioxidant enzymes SOD, GPx, and CAT were increased. The apoptotic markers caspase-3, BAX, and Bcl2 were modulated. Collectively, these findings highlight the nephroprotective competency of theaflavin against cisplatin-induced nephrotoxicity and underscore modulations of SIRT1, p53, FOXO3a, Nrf2, and NF-kB as potential targets.
{"title":"Theaflavin alleviates cisplatin-induced nephrotoxicity: Targeting SIRT1/p53/FOXO3a/Nrf2 signaling and the NF-kB inflammatory cascade","authors":"Samyah T. Alanazi , Samir A. Salama , Musaad M. Althobaiti , Afnan Bakhsh , Najla M. Aljehani , Ebtisam Alanazi , Maha T. Alanazi , Arafa Musa","doi":"10.1016/j.fct.2025.115334","DOIUrl":"10.1016/j.fct.2025.115334","url":null,"abstract":"<div><div>Cisplatin is a widely used chemotherapeutic agent. Nevertheless, a significant fraction of cisplatin-treated patients develops nephrotoxicity which limits cisplatin therapeutic implementation. The current work was devoted to investigate the potential nephroprotective impact of theaflavin against the cisplatin-induced nephrotoxicity using male Wistar rats as a mammalian model. The results indicated that theaflavin significantly improved the renal histopathological picture and glomerular filtration rate, along with reduced renal injury marker KIM-1, urinary albumin/creatinine ratio, serum creatinine, and urea. Mechanistically, theaflavin upregulated protein level of SIRT1 and downregulated the acetylated forms of the inflammatory transcription factor (TF) NF-kB, the antioxidant TF FOXO3a, and the pro-apoptotic TF p53 in the cisplatin-treated rats. Additionally, it upregulated the antioxidant TF Nrf2. In the same context, it suppressed the inflammatory responses, oxidative stress, and apoptosis. NF-kB nuclear translocation and levels of its responsive gene products IL-6 and TNF-α were suppressed. Lipids and DNA oxidation were reduced, and level of the antioxidant GSH and activity of the antioxidant enzymes SOD, GPx, and CAT were increased. The apoptotic markers caspase-3, BAX, and Bcl2 were modulated. Collectively, these findings highlight the nephroprotective competency of theaflavin against cisplatin-induced nephrotoxicity and underscore modulations of SIRT1, p53, FOXO3a, Nrf2, and NF-kB as potential targets.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"198 ","pages":"Article 115334"},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454984","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 : 2025-02-19DOI: 10.1016/j.fct.2025.115332
Amaia Irizar, Fanny Boislève, Françoise Gautier, J Frank Nash, Stefan Pfuhler, Gretchen Ritacco, Matthias Vey, Nicolas Wolf, Peter A Cadby
The phototoxicological effects of furocoumarins have been extensively studied. In association with UVA, some of these natural constituents of botanical isolates used in cosmetics, can be photoirritant, photogenotoxic and/or photocarcinogenic. Importantly, not all furocoumarins share the same degree of potency and some are inactive. The more potent furocoumarins, 8-methoxypsoralen and 5-methoxypsoralen, have been subject to extensive mechanistic studies. The formation of adducts with DNA has been widely studied but other contributary mechanisms have also been proposed. The phototoxicological effects, ranging from photoirritation to photocarcinogenicity, are dependent on the dermal dose of furocoumarin and the fluence (dose) of filtered, artificial UVA light. This is particularly evident from photocarcinogenicity studies in animals and from the effect of sequential irradiation sessions in patients receiving Psoralen-UVA (PUVA) therapy. A currently enforced limit of 1 ppm for sun bronzing and sunscreen products for which prolonged intentional exposure to UVA is likely, and 5ppm total furocoumarin concentration in other cosmetic products, e.g., facial cosmetics, that are likely to be only exposed to adventitious and intermittent UVA irradiation, provides a suitably protective threshold when compared to the UV exposure that has been used in studies on animals and in treating PUVA patients.
{"title":"Phototoxicity and skin damage: A review of adverse effects of some furocoumarins found in natural extracts.","authors":"Amaia Irizar, Fanny Boislève, Françoise Gautier, J Frank Nash, Stefan Pfuhler, Gretchen Ritacco, Matthias Vey, Nicolas Wolf, Peter A Cadby","doi":"10.1016/j.fct.2025.115332","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115332","url":null,"abstract":"<p><p>The phototoxicological effects of furocoumarins have been extensively studied. In association with UVA, some of these natural constituents of botanical isolates used in cosmetics, can be photoirritant, photogenotoxic and/or photocarcinogenic. Importantly, not all furocoumarins share the same degree of potency and some are inactive. The more potent furocoumarins, 8-methoxypsoralen and 5-methoxypsoralen, have been subject to extensive mechanistic studies. The formation of adducts with DNA has been widely studied but other contributary mechanisms have also been proposed. The phototoxicological effects, ranging from photoirritation to photocarcinogenicity, are dependent on the dermal dose of furocoumarin and the fluence (dose) of filtered, artificial UVA light. This is particularly evident from photocarcinogenicity studies in animals and from the effect of sequential irradiation sessions in patients receiving Psoralen-UVA (PUVA) therapy. A currently enforced limit of 1 ppm for sun bronzing and sunscreen products for which prolonged intentional exposure to UVA is likely, and 5ppm total furocoumarin concentration in other cosmetic products, e.g., facial cosmetics, that are likely to be only exposed to adventitious and intermittent UVA irradiation, provides a suitably protective threshold when compared to the UV exposure that has been used in studies on animals and in treating PUVA patients.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115332"},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472033","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}
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