Pub Date : 2025-01-09eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae231
Kunyu Du, Jingkui Shu, Jintao Wu, Na Liu, He Ma, Jinyun Jiang, Yuefeng He, Xinan Wu
This study explores the role of Argonaute 2 (AGO2) in the induction of apoptosis by arsenic in 16HBE cells and investigates the association between AGO2 expression and arsenic exposure in a human population. By silencing AGO2 with siRNA, we examined its impact on cell viability and apoptosis using CCK-8, HO-PI, and JC-1 assays, complemented by qRT-PCR and Western blot analyses for gene and protein expressions. Our findings revealed a significant correlation between AGO2 expression and levels of exposure to inorganic arsenic (iAs), which was more pronounced than with other arsenic forms such as monomethylarsonic (MMA) and dimethylarsinic acids (DMA). The results showed that silencing AGO2 not only reduced cell viability but also intensified apoptosis, highlighting its role in activating the p53 pathway. This was further supported by increased phosphorylation of p53 at Ser392 and Thr55, reinforcing AGO2's involvement in apoptotic processes. The study underscores the potential of AGO2 as a therapeutic target in arsenic-related pathologies and highlights the critical need for managing occupational exposure to arsenic.
{"title":"Inorganic arsenic modulates cell apoptosis by regulating Argonaute 2 expression via the p53 pathway.","authors":"Kunyu Du, Jingkui Shu, Jintao Wu, Na Liu, He Ma, Jinyun Jiang, Yuefeng He, Xinan Wu","doi":"10.1093/toxres/tfae231","DOIUrl":"10.1093/toxres/tfae231","url":null,"abstract":"<p><p>This study explores the role of Argonaute 2 (AGO2) in the induction of apoptosis by arsenic in 16HBE cells and investigates the association between AGO2 expression and arsenic exposure in a human population. By silencing AGO2 with siRNA, we examined its impact on cell viability and apoptosis using CCK-8, HO-PI, and JC-1 assays, complemented by qRT-PCR and Western blot analyses for gene and protein expressions. Our findings revealed a significant correlation between AGO2 expression and levels of exposure to inorganic arsenic (iAs), which was more pronounced than with other arsenic forms such as monomethylarsonic (MMA) and dimethylarsinic acids (DMA). The results showed that silencing AGO2 not only reduced cell viability but also intensified apoptosis, highlighting its role in activating the p53 pathway. This was further supported by increased phosphorylation of p53 at Ser392 and Thr55, reinforcing AGO2's involvement in apoptotic processes. The study underscores the potential of AGO2 as a therapeutic target in arsenic-related pathologies and highlights the critical need for managing occupational exposure to arsenic.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae231"},"PeriodicalIF":2.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae235
Linsen Zhang, Xiu Yuan, Qingmei Peng
Ovarian cancer (OC) is a significant cause of cancer-related mortality among women. This study explores the efficacy of Achillea millefolium L. (A. millefolium) extract, known for its phytoestrogenic properties, in treating OC through hormonal and metabolic modulation. Using a Wistar rat model, OC was induced with 7,12-dimethylbenz(a)anthracene (DMBA), and the effects of A. millefolium, both alone and in combination with paclitaxel (PTX), were evaluated. The study involved five groups of ten rats each: normal, OC, and those receiving 100 mg/kg of A. millefolium with or without PTX. Key hormonal levels, oxidative stress markers, and inflammatory cytokines were measured. Additionally, ovarian tissues were analyzed for malondialdehyde and ferric reducing ability of plasma, while gene and protein expressions related to apoptosis were assessed. Results showed that A. millefolium, particularly when combined with PTX, reduced the luteinizing hormone/follicle-stimulating hormone ratio, increased antioxidant enzyme activity, and upregulated apoptosis-related pathways, leading to higher p53 expression and fewer Ki-67 positive cells. These findings suggest A. millefolium's potential as a complementary therapy for women with OC, particularly those with ovulation disorders.
{"title":"Therapeutic potential of <i>Achillea millefolium</i> L. extract on 7,12-dimethylbenz(a)anthracene (DMBA) -induced ovary cancer in Wistar rats: a biochemical, molecular and histopathological approach.","authors":"Linsen Zhang, Xiu Yuan, Qingmei Peng","doi":"10.1093/toxres/tfae235","DOIUrl":"10.1093/toxres/tfae235","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a significant cause of cancer-related mortality among women. This study explores the efficacy of <i>Achillea millefolium</i> L. (<i>A. millefolium</i>) extract, known for its phytoestrogenic properties, in treating OC through hormonal and metabolic modulation. Using a Wistar rat model, OC was induced with 7,12-dimethylbenz(a)anthracene (DMBA), and the effects of <i>A. millefolium</i>, both alone and in combination with paclitaxel (PTX), were evaluated. The study involved five groups of ten rats each: normal, OC, and those receiving 100 mg/kg of <i>A. millefolium</i> with or without PTX. Key hormonal levels, oxidative stress markers, and inflammatory cytokines were measured. Additionally, ovarian tissues were analyzed for malondialdehyde and ferric reducing ability of plasma, while gene and protein expressions related to apoptosis were assessed. Results showed that <i>A. millefolium</i>, particularly when combined with PTX, reduced the luteinizing hormone/follicle-stimulating hormone ratio, increased antioxidant enzyme activity, and upregulated apoptosis-related pathways, leading to higher p53 expression and fewer Ki-67 positive cells. These findings suggest <i>A. millefolium</i>'s potential as a complementary therapy for women with OC, particularly those with ovulation disorders.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae235"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae234
Sarah S Mohammed, Ayman Zaaqoq, Shimaa Talaat, Salma I Abdelkader
The incidence of acute organophosphate (OP) poisoning has steadily increased in developing countries. Many studies showed that oxidative stress could have a significant role in its mechanism. The current study aimed to evaluate the role of N acetylcysteine (NAC) as an antioxidant in acute OP poisoned. A randomized, controlled, parallel-group trial was conducted in the period from the beginning of January 2022 to the end of June 2022. The study included 56 acute OP poisoned patients admitted to the intensive care unit (ICU) at the Poison Control Center of Ain Shams University Hospitals within 6 h after the exposure. The patients were randomly allocated in two equal groups; group (A): received the standard treatment plus NAC in a total dose of 300 mg/kg administered intravenously (IV) while group (B) received the standard treatment. Then both groups were compared as regards clinical parameters, laboratory investigations, ECG, and outcomes. Baseline parameters were comparable between the groups. However, NAC treatment significantly elevated concentrations of both serum catalase and glutathione peroxidase levels at 24 h, it did not significantly affect the total dose of atropine required, duration of atropine and oximes treatment or need for mechanical ventilation, and length of hospital stay. Mortality was lower in the NAC group (2 out of 28) than the standard treatment-only group (5 out of 28) but the difference was not statistically significant. This trial found that NAC improved antioxidant enzyme levels including serum CAT and GPX but did not affect clinically relevant outcomes.
{"title":"A randomized, clinical trial of intravenous N-acetylcysteine as an antioxidant therapy in acute organophosphorus pesticide poisoning.","authors":"Sarah S Mohammed, Ayman Zaaqoq, Shimaa Talaat, Salma I Abdelkader","doi":"10.1093/toxres/tfae234","DOIUrl":"10.1093/toxres/tfae234","url":null,"abstract":"<p><p>The incidence of acute organophosphate (OP) poisoning has steadily increased in developing countries. Many studies showed that oxidative stress could have a significant role in its mechanism. The current study aimed to evaluate the role of N acetylcysteine (NAC) as an antioxidant in acute OP poisoned. A randomized, controlled, parallel-group trial was conducted in the period from the beginning of January 2022 to the end of June 2022. The study included 56 acute OP poisoned patients admitted to the intensive care unit (ICU) at the Poison Control Center of Ain Shams University Hospitals within 6 h after the exposure. The patients were randomly allocated in two equal groups; group (A): received the standard treatment plus NAC in a total dose of 300 mg/kg administered intravenously (IV) while group (B) received the standard treatment. Then both groups were compared as regards clinical parameters, laboratory investigations, ECG, and outcomes. Baseline parameters were comparable between the groups. However, NAC treatment significantly elevated concentrations of both serum catalase and glutathione peroxidase levels at 24 h, it did not significantly affect the total dose of atropine required, duration of atropine and oximes treatment or need for mechanical ventilation, and length of hospital stay. Mortality was lower in the NAC group (2 out of 28) than the standard treatment-only group (5 out of 28) but the difference was not statistically significant. This trial found that NAC improved antioxidant enzyme levels including serum CAT and GPX but did not affect clinically relevant outcomes.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae234"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae232
Meray Medhat Shokry Zaghary, Hasnaa Ahmed Ahmed Ali, Asmaa Mohammed Khalaf Ahmed
Aluminium phosphide poison become an alarming, well-known, effective suicidal poison with a high mortality rate. There is a need for a simple tool that can triage patients with bad prognosis. The study aimed to assess the accuracy of ejection fraction as a predictor of mortality and morbidity in acute aluminium phosphide toxicity cases. The study involved 70 cases of acutely aluminium phosphide-poisoned patients in our hospital from January 2021 to January 2024. The study found that 54.3% of the cases were males and 45.7% were females, with a mean age of 22.4 ± 11.8 years old. The oral route was the route of administration of all cases, and the intention of poisoning was intentional in 84.3% of cases. Regarding the outcome of patients, 62.9% of the cases recovered, and 37.1% died. The Receiver Operating Characteristic Curve found that the ejection fraction below 37.5% had an accuracy rate of 96.8% with excellent discrimination for mortality, sensitivity of 100%, specificity of 93.2%, positive predictive value of 89.6%, and negative predictive value of 100%. The ejection fraction below 52.5% had an accuracy rate of 89% with good discrimination for complications, sensitivity of 83.3%, specificity of 96.8%, positive predictive value of 90.9%, and negative predictive value of 93.7%. So, the ejection fraction plays an essential tool in predicting mortality and complications in acute aluminium phosphide toxicity and should be assessed on every patient in the first 24 h of admission to facilitate the triage of these patients.
{"title":"The performance of ejection fraction as a predictor of mortality and morbidity in acute aluminium phosphide poisoning.","authors":"Meray Medhat Shokry Zaghary, Hasnaa Ahmed Ahmed Ali, Asmaa Mohammed Khalaf Ahmed","doi":"10.1093/toxres/tfae232","DOIUrl":"10.1093/toxres/tfae232","url":null,"abstract":"<p><p>Aluminium phosphide poison become an alarming, well-known, effective suicidal poison with a high mortality rate. There is a need for a simple tool that can triage patients with bad prognosis. The study aimed to assess the accuracy of ejection fraction as a predictor of mortality and morbidity in acute aluminium phosphide toxicity cases. The study involved 70 cases of acutely aluminium phosphide-poisoned patients in our hospital from January 2021 to January 2024. The study found that 54.3% of the cases were males and 45.7% were females, with a mean age of 22.4 ± 11.8 years old. The oral route was the route of administration of all cases, and the intention of poisoning was intentional in 84.3% of cases. Regarding the outcome of patients, 62.9% of the cases recovered, and 37.1% died. The Receiver Operating Characteristic Curve found that the ejection fraction below 37.5% had an accuracy rate of 96.8% with excellent discrimination for mortality, sensitivity of 100%, specificity of 93.2%, positive predictive value of 89.6%, and negative predictive value of 100%. The ejection fraction below 52.5% had an accuracy rate of 89% with good discrimination for complications, sensitivity of 83.3%, specificity of 96.8%, positive predictive value of 90.9%, and negative predictive value of 93.7%. So, the ejection fraction plays an essential tool in predicting mortality and complications in acute aluminium phosphide toxicity and should be assessed on every patient in the first 24 h of admission to facilitate the triage of these patients.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae232"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Our study focused on the potential mechanism of microRNA-490-3p (miR-490-3p) on learning/memory disability of rats resulting from sevoflurane (Sev). The rat model of cognitive dysfunction was established by infection with miR-490-3p mimic and Sev-exposure. Morris water maze and open field test assay were used for the assessment of cognitive deficits. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction assays were used for the measurements of neuroinflammatory cytokines and inflammatory-related genes in respective order. Bioinformatics analysis was employed for the predictive miR-490-3p-related genes. The targeted interaction was verified via dual-luciferase reporter assay. A significant decline of miR-490-3p was discovered in rats with Sev treatment, while the levels were up-regulated in rats with infection miR-490-3p pretreatment (P < 0.001). For Sev-induced rats, the stay time in the target quadrant was shorten, while distance travelled lengthened significantly with the control group by comparison (P < 0.001). Notably, an increased time of the escape latency and a decreased number of platform crossings were found in the Sev group, which alleviated by infection with miR-490-3p mimic pretreatment (P < 0.001). Moreover, the neuroinflammatory cytokines were elevated in the Sev group, the effects of which were recovered via miR-490-3p pretreatment (P < 0.001). Bioinformatics analysis predicted the miR-490-3p-associated genes. CDK1 (Cyclin-dependent kinase 1) was a potential target gene of miR-490-3p, which confirmed by dual-luciferase reporter detection. MiR-490-3p alleviated the learning and memory deficits in Sev-treated rats via the modulation of CDK1.
{"title":"Up-regulation of miR-490-3p improves learning/memory disability of sevoflurane exposure by relieving neuroinflammation.","authors":"Shuang Zhai, Ying Li, Aili Guo, Wei Zhao, Changliang Mou","doi":"10.1093/toxres/tfae226","DOIUrl":"10.1093/toxres/tfae226","url":null,"abstract":"<p><p>Our study focused on the potential mechanism of microRNA-490-3p (miR-490-3p) on learning/memory disability of rats resulting from sevoflurane (Sev). The rat model of cognitive dysfunction was established by infection with miR-490-3p mimic and Sev-exposure. Morris water maze and open field test assay were used for the assessment of cognitive deficits. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction assays were used for the measurements of neuroinflammatory cytokines and inflammatory-related genes in respective order. Bioinformatics analysis was employed for the predictive miR-490-3p-related genes. The targeted interaction was verified via dual-luciferase reporter assay. A significant decline of miR-490-3p was discovered in rats with Sev treatment, while the levels were up-regulated in rats with infection miR-490-3p pretreatment (<i>P</i> < 0.001). For Sev-induced rats, the stay time in the target quadrant was shorten, while distance travelled lengthened significantly with the control group by comparison (<i>P</i> < 0.001). Notably, an increased time of the escape latency and a decreased number of platform crossings were found in the Sev group, which alleviated by infection with miR-490-3p mimic pretreatment (<i>P</i> < 0.001). Moreover, the neuroinflammatory cytokines were elevated in the Sev group, the effects of which were recovered via miR-490-3p pretreatment (<i>P</i> < 0.001). Bioinformatics analysis predicted the miR-490-3p-associated genes. CDK1 (Cyclin-dependent kinase 1) was a potential target gene of miR-490-3p, which confirmed by dual-luciferase reporter detection. MiR-490-3p alleviated the learning and memory deficits in Sev-treated rats via the modulation of CDK1.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae226"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae230
Ola Elsayed Nafea, Fatma Ibrahim, Walaa G Abdelhamid
Acute aluminum phosphide (AlP) poisoning is one of the leading causes of suicide, particularly in the developing world. In cases of scarce and/or high-cost resources, it is advisable to prioritize critically ill patients who will benefit from available resources and improve their prognosis. Despite numerous scores, a dependable, easy-to-use, and quick approach to assessing the degree of poisoning is lacking. This study is designed to compare the prognostic performance of the National Early Warning Score 2 (NEWS2) versus the new-poisoning mortality score system (new-PMS) for predicting the clinical outcomes, including in-hospital mortality, vasopressor use, and mechanical ventilation placement after acute AlP poisoning. This study was a retrospective observational study that included patients with acute AlP poisoning with retrieving the required data from the patients' medical records. A total of 90 acutely AlP-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 42.2%. Additionally, in-hospital mortality, vasopressor use, and mechanical ventilation placement were significantly higher in patients with higher NEWS2 and new-PMS scores. The new-PMS showed excellent prognostic performance, particularly in-hospital mortality prediction; however, NEWS2 demonstrated a more helpful predictive performance compared to the new-PMS particularly for the need for mechanical ventilation and in-hospital mortality, with an area under the curve of 0.991 versus 0.851 and 0.949 versus 0.874, respectively. We concluded that NEWS2 and new-PMS are simple, easily calculated, and lab-independent scoring systems. The NEWS2 is a more effective tracking and triggering tool than the new-PMS in the evaluation of AlP acutely intoxicated patients.
{"title":"The National Early Warning Score 2 versus the New-Poisoning Mortality Score System for Predicting Clinical Outcomes After Acute Aluminum Phosphide Poisoning.","authors":"Ola Elsayed Nafea, Fatma Ibrahim, Walaa G Abdelhamid","doi":"10.1093/toxres/tfae230","DOIUrl":"10.1093/toxres/tfae230","url":null,"abstract":"<p><p>Acute aluminum phosphide (AlP) poisoning is one of the leading causes of suicide, particularly in the developing world. In cases of scarce and/or high-cost resources, it is advisable to prioritize critically ill patients who will benefit from available resources and improve their prognosis. Despite numerous scores, a dependable, easy-to-use, and quick approach to assessing the degree of poisoning is lacking. This study is designed to compare the prognostic performance of the National Early Warning Score 2 (NEWS2) versus the new-poisoning mortality score system (new-PMS) for predicting the clinical outcomes, including in-hospital mortality, vasopressor use, and mechanical ventilation placement after acute AlP poisoning. This study was a retrospective observational study that included patients with acute AlP poisoning with retrieving the required data from the patients' medical records. A total of 90 acutely AlP-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 42.2%. Additionally, in-hospital mortality, vasopressor use, and mechanical ventilation placement were significantly higher in patients with higher NEWS2 and new-PMS scores. The new-PMS showed excellent prognostic performance, particularly in-hospital mortality prediction; however, NEWS2 demonstrated a more helpful predictive performance compared to the new-PMS particularly for the need for mechanical ventilation and in-hospital mortality, with an area under the curve of 0.991 versus 0.851 and 0.949 versus 0.874, respectively. We concluded that NEWS2 and new-PMS are simple, easily calculated, and lab-independent scoring systems. The NEWS2 is a more effective tracking and triggering tool than the new-PMS in the evaluation of AlP acutely intoxicated patients.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae230"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-07eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae228
Shiv Kumar, Pooja Chadha
Polybrominated diphenyl ethers (PBDEs) have been classified as a new class of persistent organic pollutants by the United Nations Environment Programs in 2009. In environment, PBDEs can undergo the degradation process to form less brominated diphenyl ethers. In the present study, the 96 h LC50 value for 4-bromodiphenyl ether (BDE-3) was found to be 3.18 mg/L in zebrafish embryo-larvae. Further, zebrafish embryo-larvae was exposed to sublethal concentrations i.e. 0.79 mg/L and 1.59 mg/L of BDE-3 to evaluate the developmental toxicity. BDE-3 significantly increased the mortality rate and decreased hatchability rate in a concentration and time-dependent manner at sublethal concentrations compared to control. Heart rate was found to be significantly decreased whereas the sinus venosus- bulbus arteriosus (SV-BA) distance found to be significantly increased in both BDE-3 exposed groups. The sensorimotor response and spontaneous movement were significantly decreased in BDE-3 exposed larvae compared to control group. A significant DNA damage was also found to be caused in BDE-3 exposed groups after the acute exposure. The current report highlights the toxicity potential of BDE-3 in the early life stages of zebrafish and hence puts up to their environmental risk assessment.
{"title":"Teratogenicity, cardiac toxicity, neurotoxicity and genotoxicity in zebrafish embryo-larvae exposed to 4-bromodiphenyl ether.","authors":"Shiv Kumar, Pooja Chadha","doi":"10.1093/toxres/tfae228","DOIUrl":"https://doi.org/10.1093/toxres/tfae228","url":null,"abstract":"<p><p>Polybrominated diphenyl ethers (PBDEs) have been classified as a new class of persistent organic pollutants by the United Nations Environment Programs in 2009. In environment, PBDEs can undergo the degradation process to form less brominated diphenyl ethers. In the present study, the 96 h LC<sub>50</sub> value for 4-bromodiphenyl ether (BDE-3) was found to be 3.18 mg/L in zebrafish embryo-larvae. Further, zebrafish embryo-larvae was exposed to sublethal concentrations i.e. 0.79 mg/L and 1.59 mg/L of BDE-3 to evaluate the developmental toxicity. BDE-3 significantly increased the mortality rate and decreased hatchability rate in a concentration and time-dependent manner at sublethal concentrations compared to control. Heart rate was found to be significantly decreased whereas the sinus venosus- bulbus arteriosus (SV-BA) distance found to be significantly increased in both BDE-3 exposed groups. The sensorimotor response and spontaneous movement were significantly decreased in BDE-3 exposed larvae compared to control group. A significant DNA damage was also found to be caused in BDE-3 exposed groups after the acute exposure. The current report highlights the toxicity potential of BDE-3 in the early life stages of zebrafish and hence puts up to their environmental risk assessment.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae228"},"PeriodicalIF":2.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-07eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae229
Reham Al Horani, Demet Dogan
Aclonifen is a diphenyl ether herbicide being included in the list of priority substances. Nevertheless, the data related to its sublethal effects on fish are limited. Therefore, the present study has been carried out to investigate the toxic effects of aclonifen in juvenile Oncorhynchus mykiss following 24, 48, 72 and 96 hours of application to sublethal concentrations of 12.7, 63.5 and 127 μg/L. The application resulted in altered blood biochemistry appearing as hyperglycemia, decreased cholesterol and induced activities of transaminases of ALT and AST. The inhibition of AChE in brain, gill and liver was unimportant revealing its weak potential as anticholinesterase. The induction recorded for SOD, CAT, GPx and GST activities was accompanied with sustained elevation in TBARS and PC levels. It demonstrates both the pro-oxidant potential of aclonifen and oxidation of lipid and proteins resulting in the loss of membrane integrity and protein function. Hyperglycemic condition and decreased protein levels in gill and liver might be proposed as general adaptive responses to compensate increased energy demand. The integrative assessment of multi-biomarker responses shows concentration and duration related rise in calculated indexes. CAT, PC and SOD achieved the maximum scores for brain, gill and liver, respectively. Considering the results, oxidative stress inducing potential and weak anticholinesterase activity along with its disturbing impact on blood biochemistry were evidenced. Moreover, adverse affects observed after short term application on O. mykiss, present the potential risk aclonifen may cause at population level in aquatic ecosystems emphasizing the importance of pesticide regulations to avoid adverse impacts on non-target species.
{"title":"Impact of sub-lethal Aclonifen intoxication on biochemical and stress markers on <i>Oncorhynchus mykiss</i>: an integrative assessment of multi-biomarker responses.","authors":"Reham Al Horani, Demet Dogan","doi":"10.1093/toxres/tfae229","DOIUrl":"https://doi.org/10.1093/toxres/tfae229","url":null,"abstract":"<p><p>Aclonifen is a diphenyl ether herbicide being included in the list of priority substances. Nevertheless, the data related to its sublethal effects on fish are limited. Therefore, the present study has been carried out to investigate the toxic effects of aclonifen in juvenile <i>Oncorhynchus mykiss</i> following 24, 48, 72 and 96 hours of application to sublethal concentrations of 12.7, 63.5 and 127 μg/L. The application resulted in altered blood biochemistry appearing as hyperglycemia, decreased cholesterol and induced activities of transaminases of ALT and AST. The inhibition of AChE in brain, gill and liver was unimportant revealing its weak potential as anticholinesterase. The induction recorded for SOD, CAT, GPx and GST activities was accompanied with sustained elevation in TBARS and PC levels. It demonstrates both the pro-oxidant potential of aclonifen and oxidation of lipid and proteins resulting in the loss of membrane integrity and protein function. Hyperglycemic condition and decreased protein levels in gill and liver might be proposed as general adaptive responses to compensate increased energy demand. The integrative assessment of multi-biomarker responses shows concentration and duration related rise in calculated indexes. CAT, PC and SOD achieved the maximum scores for brain, gill and liver, respectively. Considering the results, oxidative stress inducing potential and weak anticholinesterase activity along with its disturbing impact on blood biochemistry were evidenced. Moreover, adverse affects observed after short term application on <i>O. mykiss</i>, present the potential risk aclonifen may cause at population level in aquatic ecosystems emphasizing the importance of pesticide regulations to avoid adverse impacts on non-target species.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae229"},"PeriodicalIF":2.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ginkgo biloba extract (GBE), a therapeutic drug, has anti-inflammatory and antioxidant effects that protect cells from harmful substances. Although GBE has been extensively studied in the prevention and treatment of lung diseases, its mechanism of action in chronic obstructive pulmonary disease (COPD) is unclear. In the present study, cigarette smoke extract (CSE) and cigarette smoke (CS) were used to induce COPD in cell and animal models. The expression of related genes and proteins was detected, and cell damage and lung tissue damage were evaluated via CCK-8 assays, flow cytometry analyses, ELISA, and HE staining. In HBE cells, the expression of miR-3,619-5p was upregulated after CSE induction. However, GBE treatment alleviated the impact of CSE on HBE cell damage and alleviated COPD in vivo. In addition, GBE treatment increased the expression of GPX4 by inhibiting the expression of miR-3,619-5p, and it reduced the release of the IL-6, IL-8, and TNF-α inflammatory factors. Moreover, GBE treatment decreased the production of ROS and MDA, as well as decreased the expression of the ferroptosis-related protein ACSL4, and it promoted the production of GSH and the expression of FTH1. Further, GBE treatment improved cell viability, inhibited ferroptosis, and ultimately alleviated COPD. The present findings suggest that GBE alleviates the progression of COPD through the inhibitory effect of the miR-3,619-5p/GPX4 axis on the ferroptosis process and that GBE may be an effective treatment option for COPD.
{"title":"<i>Ginkgo biloba</i> extract alleviates ferroptosis in lung epithelial cells induced by cigarette smoke extract through miR-3,619-5p/GPX4 axis.","authors":"Anhui Xu, Yanmei Xu, Hongbo Chen, Linhua Xiang, Xiao Zhao","doi":"10.1093/toxres/tfae225","DOIUrl":"https://doi.org/10.1093/toxres/tfae225","url":null,"abstract":"<p><p><i>Ginkgo biloba</i> extract (GBE), a therapeutic drug, has anti-inflammatory and antioxidant effects that protect cells from harmful substances. Although GBE has been extensively studied in the prevention and treatment of lung diseases, its mechanism of action in chronic obstructive pulmonary disease (COPD) is unclear. In the present study, cigarette smoke extract (CSE) and cigarette smoke (CS) were used to induce COPD in cell and animal models. The expression of related genes and proteins was detected, and cell damage and lung tissue damage were evaluated via CCK-8 assays, flow cytometry analyses, ELISA, and HE staining. In HBE cells, the expression of miR-3,619-5p was upregulated after CSE induction. However, GBE treatment alleviated the impact of CSE on HBE cell damage and alleviated COPD in vivo. In addition, GBE treatment increased the expression of GPX4 by inhibiting the expression of miR-3,619-5p, and it reduced the release of the IL-6, IL-8, and TNF-α inflammatory factors. Moreover, GBE treatment decreased the production of ROS and MDA, as well as decreased the expression of the ferroptosis-related protein ACSL4, and it promoted the production of GSH and the expression of FTH1. Further, GBE treatment improved cell viability, inhibited ferroptosis, and ultimately alleviated COPD. The present findings suggest that GBE alleviates the progression of COPD through the inhibitory effect of the miR-3,619-5p/GPX4 axis on the ferroptosis process and that GBE may be an effective treatment option for COPD.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae225"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kombucha is fermented and produced with a biofilm called a symbiotic culture of bacteria and yeast, which is drunk all over the world for its beneficial effects on human health and energy levels. The metagenomic study of kombucha frequently detected microorganisms in proteobacteria, firmicutes, and actinobacteria. And also, yeast and fungi are Ascomycota and Basidiomycota is present in green leaf and sugarcane juice fermented kombucha. The kombucha extracts' biological activities were assessed using pH, total phenolic content, antioxidant, antibacterial, and anticancer activity. Fermentation may enhance biological activity and the generation of bioactive substances. These results showed the pH -3.1 ± 0.2 and TPC -0.721 μg/mL of gallic acid equivalent. The antioxidant radicals scavenging activity of kombucha was evaluated by DPPH, ABTS, H2O2 and TAC. The bioactive chemicals identified by FT-IR and HR-LC/MS analysis of Kombucha totaled 45 components. The identified compounds were further move on to perform molecular docking study against gastric cancer target proteins 4H9M, 2DQ7 and 1TVO are binding with Nequinate compounds showing best LibDock scores 105.12, 114.49, and 108.97. So, this study suggests that knowledge can potentially active bioactive compounds are present in kombucha and it's stimulated the mechanism of gastrointestinal transit. Additionally, the metagenomic analysis gives strength to understand the bacterial and fungal distribution and its molecular mechanism from Kombucha.
{"title":"Metagenomic analysis and bioactive profiling of kombucha fermentation: antioxidant, antibacterial activities, and molecular docking insights into gastric cancer therapeutics.","authors":"Thavasiaanatham Seenivasan Shalini, Ragothaman Prathiviraj, Poomalai Senthilraja","doi":"10.1093/toxres/tfae224","DOIUrl":"10.1093/toxres/tfae224","url":null,"abstract":"<p><p>Kombucha is fermented and produced with a biofilm called a symbiotic culture of bacteria and yeast, which is drunk all over the world for its beneficial effects on human health and energy levels. The metagenomic study of kombucha frequently detected microorganisms in proteobacteria, firmicutes, and actinobacteria. And also, yeast and fungi are Ascomycota and Basidiomycota is present in green leaf and sugarcane juice fermented kombucha. The kombucha extracts' biological activities were assessed using pH, total phenolic content, antioxidant, antibacterial, and anticancer activity. Fermentation may enhance biological activity and the generation of bioactive substances. These results showed the pH -3.1 ± 0.2 and TPC -0.721 μg/mL of gallic acid equivalent. The antioxidant radicals scavenging activity of kombucha was evaluated by DPPH, ABTS, H<sub>2</sub>O<sub>2</sub> and TAC. The bioactive chemicals identified by FT-IR and HR-LC/MS analysis of Kombucha totaled 45 components. The identified compounds were further move on to perform molecular docking study against gastric cancer target proteins 4H9M, 2DQ7 and 1TVO are binding with Nequinate compounds showing best LibDock scores 105.12, 114.49, and 108.97. So, this study suggests that knowledge can potentially active bioactive compounds are present in kombucha and it's stimulated the mechanism of gastrointestinal transit. Additionally, the metagenomic analysis gives strength to understand the bacterial and fungal distribution and its molecular mechanism from Kombucha.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae224"},"PeriodicalIF":2.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}