Pub Date : 2025-01-19DOI: 10.1016/j.toxrep.2025.101917
Gildênia Alves de Araújo , Cícera Datiane de Morais Oliveira Tintino , Raimundo Luíz Silva Pereira , Isaac Moura Araújo , Cícera Laura Roque Paulo , João Arthur de Oliveira Borges , Ewerton Yago de Sousa Rodrigues , Ângella Eduarda da Silva , Francisco Assis Bezerra da Cunha , Zildene de Sousa Silveira , Nair Silva Macedo , Henrique Douglas Melo Coutinho , José Maria Barbosa Filho , Daniela Maria do Amaral Ferraz Navarro , Francisco Roberto de Azevedo , Saulo Relison Tintino
This study aimed to evaluate the antibacterial activity against multi-drug-resistant strains carrying efflux pumps and assess their toxicity on Drosophila melanogaster and Aedes aegypti models. Microdilution tests in broth were performed to determine the Minimum Inhibitory Concentration (MIC). The efflux pump inhibition was evaluated by analyzing the reduction in antibiotic MIC and Ethidium Bromide (EtBr) MIC when combined with the products. Mortality assay and negative geotaxis were conducted on D. melanogaster specimens, and insecticidal activity assays were performed on A. aegypti larvae. Only geraniol reduced the antibiotic MIC when combined, reducing from 64 µg/mL to 16 µg/mL in the 1199B strain of S. aureus. When combined with EtBr, both geraniol and citral reduced EtBr MIC, with geraniol decreasing from 64 µg/mL to 16 µg/mL and citral decreasing from 64 µg/mL to 32 µg/mL. Regarding the S. aureus K2068 strain, geraniol reduced the antibiotic MIC from 16 µg/mL to 8 µg/mL, and citral reduced it from 16 µg/mL to 4 µg/mL. In combination with EtBr, all monoterpenes reduced MIC from 64 µg/mL to 32 µg/mL. Both products exhibited toxicity in D. melanogaster; however, citral showed higher toxicity with a precisely determined LC50 of 2.478 μL. As for the insecticidal action on A. aegypti, both products demonstrated toxicity with cumulative effects and dose-dependent mortality.
{"title":"Toxicological assessment of citral and geraniol: Efflux pump inhibition in Staphylococcus aureus and invertebrate toxicity","authors":"Gildênia Alves de Araújo , Cícera Datiane de Morais Oliveira Tintino , Raimundo Luíz Silva Pereira , Isaac Moura Araújo , Cícera Laura Roque Paulo , João Arthur de Oliveira Borges , Ewerton Yago de Sousa Rodrigues , Ângella Eduarda da Silva , Francisco Assis Bezerra da Cunha , Zildene de Sousa Silveira , Nair Silva Macedo , Henrique Douglas Melo Coutinho , José Maria Barbosa Filho , Daniela Maria do Amaral Ferraz Navarro , Francisco Roberto de Azevedo , Saulo Relison Tintino","doi":"10.1016/j.toxrep.2025.101917","DOIUrl":"10.1016/j.toxrep.2025.101917","url":null,"abstract":"<div><div>This study aimed to evaluate the antibacterial activity against multi-drug-resistant strains carrying efflux pumps and assess their toxicity on <em>Drosophila melanogaster</em> and <em>Aedes aegypti</em> models. Microdilution tests in broth were performed to determine the Minimum Inhibitory Concentration (MIC). The efflux pump inhibition was evaluated by analyzing the reduction in antibiotic MIC and Ethidium Bromide (EtBr) MIC when combined with the products. Mortality assay and negative geotaxis were conducted on <em>D. melanogaster</em> specimens, and insecticidal activity assays were performed on <em>A. aegypti</em> larvae. Only geraniol reduced the antibiotic MIC when combined, reducing from 64 µg/mL to 16 µg/mL in the 1199B strain of <em>S. aureus</em>. When combined with EtBr, both geraniol and citral reduced EtBr MIC, with geraniol decreasing from 64 µg/mL to 16 µg/mL and citral decreasing from 64 µg/mL to 32 µg/mL. Regarding the <em>S. aureus</em> K2068 strain, geraniol reduced the antibiotic MIC from 16 µg/mL to 8 µg/mL, and citral reduced it from 16 µg/mL to 4 µg/mL. In combination with EtBr, all monoterpenes reduced MIC from 64 µg/mL to 32 µg/mL. Both products exhibited toxicity in <em>D. melanogaster</em>; however, citral showed higher toxicity with a precisely determined LC50 of 2.478 μL. As for the insecticidal action on <em>A. aegypti</em>, both products demonstrated toxicity with cumulative effects and dose-dependent mortality.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101917"},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1016/j.toxrep.2025.101895
Tohada M. AL-Noshokaty , Rehab Abdelhamid , Nourhan M. Abdelmaksoud , Aya Khaled , Mariam Hossam , Razan Ahmed , Toka Saber , Shahd Khaled , Shereen Saeid Elshaer , Ahmed I. Abulsoud
Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and a promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, and satiety. We examine the compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) in managing type 2 diabetes (T2D), obesity, and other diseases. The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways like extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein kinase (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Expanding our understanding, the review investigates the potential role of GLP-1 in cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators of gene expression, are introduced as potential modulators of GLP-1 signaling. We delve into the link between miRNAs and T2D obesity and explore specific miRNA examples influencing GLP-1R function. Finally, the review explores the rationale for seeking alternatives to GLP-1RAs and highlights natural products with promising GLP-1 modulatory effects.
{"title":"Unlocking the multifaceted roles of GLP-1: Physiological functions and therapeutic potential","authors":"Tohada M. AL-Noshokaty , Rehab Abdelhamid , Nourhan M. Abdelmaksoud , Aya Khaled , Mariam Hossam , Razan Ahmed , Toka Saber , Shahd Khaled , Shereen Saeid Elshaer , Ahmed I. Abulsoud","doi":"10.1016/j.toxrep.2025.101895","DOIUrl":"10.1016/j.toxrep.2025.101895","url":null,"abstract":"<div><div>Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and a promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, and satiety. We examine the compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) in managing type 2 diabetes (T2D), obesity, and other diseases. The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways like extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein kinase (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Expanding our understanding, the review investigates the potential role of GLP-1 in cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators of gene expression, are introduced as potential modulators of GLP-1 signaling. We delve into the link between miRNAs and T2D obesity and explore specific miRNA examples influencing GLP-1R function. Finally, the review explores the rationale for seeking alternatives to GLP-1RAs and highlights natural products with promising GLP-1 modulatory effects.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101895"},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143099193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Formaldehyde is widely used for the preservation of cadavers, exposing workers to potential risks of formaldehyde exposure in the workplace. This study compared the performance of real-time instruments (Gasmet) and absorbent tube methods in controlling formaldehyde levels in gross anatomy dissections with four working process areas. The concentrations of formaldehyde were determined over working periods ranging from 2 to 5 h. For the Gasmet results, a Monte Carlo simulation was applied in the uncertainty analysis to predict the formaldehyde concentration. Data collection involved questionnaires that included personal and work-related information. The Wilcoxon matched-pairs signed-rank test and intraclass correlation coefficients (ICC) were used to test–retest reliability between the two instruments. The results showed that the Gasmet direct reading and absorbent tube concentrations were not significantly different (p > 0.05) in all working areas and ICC was 0.939 indicating a highly reliable test result between the two measurements. The health-risk estimation indicated the hazard quotient and carcinogenic risk of formaldehyde. The carcinogenic risk was found to be unacceptable for all staff and processes, while the hazard quotient was found to be acceptable only in the body injection process. Future studies should employ a larger sample size and a greater number of sampling points to enhance the statistical power and precision of the results. The findings of this study can be used to improve work environments and develop strategies to reduce the risks for staff who work in gross anatomy dissections.
{"title":"Comparison of real-time instrument use and absorbent tube method for measuring formaldehyde in working environments: A health risk assessment for gross anatomy staff","authors":"Phanpina Soonklang , Arroon Ketsakorn , Nontiya Homkham , Chalermchai Chaikittiporn , Saowanee Norkaew","doi":"10.1016/j.toxrep.2025.101913","DOIUrl":"10.1016/j.toxrep.2025.101913","url":null,"abstract":"<div><div>Formaldehyde is widely used for the preservation of cadavers, exposing workers to potential risks of formaldehyde exposure in the workplace. This study compared the performance of real-time instruments (Gasmet) and absorbent tube methods in controlling formaldehyde levels in gross anatomy dissections with four working process areas. The concentrations of formaldehyde were determined over working periods ranging from 2 to 5 h. For the Gasmet results, a Monte Carlo simulation was applied in the uncertainty analysis to predict the formaldehyde concentration. Data collection involved questionnaires that included personal and work-related information. The Wilcoxon matched-pairs signed-rank test and intraclass correlation coefficients (ICC) were used to test–retest reliability between the two instruments. The results showed that the Gasmet direct reading and absorbent tube concentrations were not significantly different (<em>p</em> > 0.05) in all working areas and ICC was 0.939 indicating a highly reliable test result between the two measurements. The health-risk estimation indicated the hazard quotient and carcinogenic risk of formaldehyde. The carcinogenic risk was found to be unacceptable for all staff and processes, while the hazard quotient was found to be acceptable only in the body injection process. Future studies should employ a larger sample size and a greater number of sampling points to enhance the statistical power and precision of the results. The findings of this study can be used to improve work environments and develop strategies to reduce the risks for staff who work in gross anatomy dissections.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101913"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143099192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14DOI: 10.1016/j.toxrep.2025.101911
Boima Situmeang , Respati Tri Swasono , Tri Joko Raharjo
Tristaniopsis merguensis is a member of the Myrtaceae family. The leaves of T. merguensis are frequently utilized as herbal tea. The study aimed to evaluate the polyphenolic content, antioxidant, and cytotoxic properties of ethyl acetate fractions derived from Tristaniopsis merguensis (ETM). In addition, it also aimed to conduct an LC-HRMS analysis of a potential fraction to ascertain its suitability as an antioxidant and anticancer active ingredient. An antioxidant evaluation was carried out using the ABTS and DPPH methods. Meanwhile, an in silico study was performed using the target protein elastase (HER-2). A total of twenty metabolites of T. merguensis were identified in the potential fraction ETM.05. In antioxidant testing, the T. merguensis fraction, with code ETM.05, demonstrated potent antioxidant activity based on the ABTS and DPPH methods, with IC50 values of 64.830 ± 2.803 µg/mL and 40.252 ± 0.032 µg/mL, respectively. This resulted in the categorization of the fraction as a strong antioxidant. In the anticancer testing, ETM.05 also demonstrated potent anticancer activity, with an IC50 value of 10.66 µg/mL, which was categorized as a very strong activity in comparison to the positive control (cisplatin), which exhibited an IC50 value of 12.24 µg/mL. The in silico study indicates that the identified metabolites have the potential to bind to the target protein HER-2, which plays a role in remodeling the breast cancer process. This research suggests that the fraction ETM.05 from the ethyl acetate leaves fraction of T. merguensis has the potential to serve as an active antioxidant and anticancer source.
{"title":"Evaluation of phytochemical composition, antioxidant, cytotoxic and in silico studies of ethyl acetate fractions of Tristaniopsis merguensis leaves","authors":"Boima Situmeang , Respati Tri Swasono , Tri Joko Raharjo","doi":"10.1016/j.toxrep.2025.101911","DOIUrl":"10.1016/j.toxrep.2025.101911","url":null,"abstract":"<div><div><em>Tristaniopsis merguensis</em> is a member of the <em>Myrtaceae</em> family. The leaves of <em>T. merguensis</em> are frequently utilized as herbal tea. The study aimed to evaluate the polyphenolic content, antioxidant, and cytotoxic properties of ethyl acetate fractions derived from <em>Tristaniopsis merguensis</em> (ETM). In addition, it also aimed to conduct an LC-HRMS analysis of a potential fraction to ascertain its suitability as an antioxidant and anticancer active ingredient. An antioxidant evaluation was carried out using the ABTS and DPPH methods. Meanwhile, an in silico study was performed using the target protein elastase (HER-2). A total of twenty metabolites of <em>T. merguensis</em> were identified in the potential fraction ETM.05. In antioxidant testing, the <em>T. merguensis</em> fraction, with code ETM.05, demonstrated potent antioxidant activity based on the ABTS and DPPH methods, with IC<sub>50</sub> values of 64.830 ± 2.803 µg/mL and 40.252 ± 0.032 µg/mL, respectively. This resulted in the categorization of the fraction as a strong antioxidant. In the anticancer testing, ETM.05 also demonstrated potent anticancer activity, with an IC<sub>50</sub> value of 10.66 µg/mL, which was categorized as a very strong activity in comparison to the positive control (cisplatin), which exhibited an IC<sub>50</sub> value of 12.24 µg/mL. The in silico study indicates that the identified metabolites have the potential to bind to the target protein HER-2, which plays a role in remodeling the breast cancer process. This research suggests that the fraction ETM.05 from the ethyl acetate leaves fraction of <em>T. merguensis</em> has the potential to serve as an active antioxidant and anticancer source.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101911"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benzophenone (BP) is an organic ultraviolet (UV) filter widely used in sunscreens and personal care products. This compound enters aquatic ecosystems due to industrialization, wastewater treatment plants (WWTPs), and domestic effluents, poses serious threats to aquatic organisms, and is considered an emerging pollutant. This laboratory-based study assessed the 96-hour (h) median lethal concentrations (LC50) and sub-lethal effects of BP on the histology of the gills and muscles of Labeo rohita. Fish fingerlings of the same weight (48 ± 2 g) and length (5 ± 2 in.) were exposed to gradually increasing concentrations of BP (100 µg/L to 1000 µg/L) and their 96-h LC50 was determined as 612.822 ± 37.38 µg/L. To determine the sub-lethal effects, the fish were exposed to 1/5th of the 96-h LC50 of BP for 35 days (d) to investigate organ-specific responses. The results indicated significant damage to the exposed organs and showed damage in pillar cells and intraluminal debris in gill mucous cells. Moreover, fragmentation of intact muscle structures, intraluminal debris, and vascular necrosis were observed in exposed muscles. In conclusion, these results confirmed the histopathological changes in the gills and muscles of L. rohita caused by BP exposure, thereby confirming its risk to aquatic life.
{"title":"Evaluation of toxic effects of benzophenone on histopathology of Labeo rohita","authors":"Maham Riaz , Sajid Abdullah , Mina Jamil , Amna Rasheed , Urwah Sheikh , Maham Fatima , Nimra Umer , Kaynat Aslam","doi":"10.1016/j.toxrep.2025.101914","DOIUrl":"10.1016/j.toxrep.2025.101914","url":null,"abstract":"<div><div>Benzophenone (BP) is an organic ultraviolet (UV) filter widely used in sunscreens and personal care products. This compound enters aquatic ecosystems due to industrialization, wastewater treatment plants (WWTPs), and domestic effluents, poses serious threats to aquatic organisms, and is considered an emerging pollutant. This laboratory-based study assessed the 96-hour (h) median lethal concentrations (LC<sub>50</sub>) and sub-lethal effects of BP on the histology of the gills and muscles of <em>Labeo rohita</em>. Fish fingerlings of the same weight (48 ± 2 g) and length (5 ± 2 in.) were exposed to gradually increasing concentrations of BP (100 µg/L to 1000 µg/L) and their 96-h LC<sub>50</sub> was determined as 612.822 ± 37.38 µg/L. To determine the sub-lethal effects, the fish were exposed to 1/5th of the 96-h LC<sub>50</sub> of BP for 35 days (d) to investigate organ-specific responses. The results indicated significant damage to the exposed organs and showed damage in pillar cells and intraluminal debris in gill mucous cells. Moreover, fragmentation of intact muscle structures, intraluminal debris, and vascular necrosis were observed in exposed muscles<em>.</em> In conclusion, these results confirmed the histopathological changes in the gills and muscles of <em>L. rohita</em> caused by BP exposure, thereby confirming its risk to aquatic life.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101914"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14DOI: 10.1016/j.toxrep.2025.101908
Andrey A. Korchevskiy , Ann G. Wylie
Introduction
Amphiboles are a class of minerals that are abundantly present in the environment. Amphiboles may exist in several habits, with asbestiform particles behaving like typical amphibole asbestos and non-asbestiform (or massive) reported to be less biologically active.
Materials and methods
The available dimensional information for 16 testing sets (8 asbestiform and 8 non-asbestiform types of tremolite) was combined. In addition, three validation sets (an asbestiform sample from Eastern New York and non-asbestiform samples from Quebec and Falls Village, Connecticut) were tested by Transmission Electron Microscopy (TEM) to determine dimensional distribution. Mathematical modeling was utilized to determine the classification method for amphiboles with various habits.
Results
The decision boundary method was developed to distinguish asbestiform vs. non-asbestiform samples (with error rate of 0 % for single-sourced tremolite and 3 % for potentially mixed samples). All validation datasets were correctly classified. A new empirical dimensional coefficient of carcinogenicity (DCC) was proposed, with DCC = 1 - exp(-0.11 Surface Area /(1000width3 + 1)). For several mineral types (crocidolite, amosite, Libby amphiboles, anthophyllite, chrysotile, and erionite), it was demonstrated that mesothelioma potency factors can be predicted based on DCC and biosolubility with a high level of accuracy (R=0.98, R2=0.96, p < 0.006). It was demonstrated that modeled mesothelioma potency correlates with relative potency for pleural instillation in Wistar rats, and correlates inversely with membranolytic toxicity index HC50. Mesothelioma potency was demonstrated to be negligible in all non-asbestiform sets.
Conclusions
The habit of amphibole particles is predictive of biological behavior that can be estimated from the dimensional data for the particles.
{"title":"Habit of elongate amphibole particles as a predictor of mesothelial carcinogenicity","authors":"Andrey A. Korchevskiy , Ann G. Wylie","doi":"10.1016/j.toxrep.2025.101908","DOIUrl":"10.1016/j.toxrep.2025.101908","url":null,"abstract":"<div><h3>Introduction</h3><div>Amphiboles are a class of minerals that are abundantly present in the environment. Amphiboles may exist in several habits, with asbestiform particles behaving like typical amphibole asbestos and non-asbestiform (or massive) reported to be less biologically active.</div></div><div><h3>Materials and methods</h3><div>The available dimensional information for 16 testing sets (8 asbestiform and 8 non-asbestiform types of tremolite) was combined. In addition, three validation sets (an asbestiform sample from Eastern New York and non-asbestiform samples from Quebec and Falls Village, Connecticut) were tested by Transmission Electron Microscopy (TEM) to determine dimensional distribution. Mathematical modeling was utilized to determine the classification method for amphiboles with various habits.</div></div><div><h3>Results</h3><div>The decision boundary method was developed to distinguish asbestiform vs. non-asbestiform samples (with error rate of 0 % for single-sourced tremolite and 3 % for potentially mixed samples). All validation datasets were correctly classified. A new empirical dimensional coefficient of carcinogenicity (DCC) was proposed, with DCC = 1 - exp(-0.11 Surface Area /(1000width<sup>3</sup> + 1)). For several mineral types (crocidolite, amosite, Libby amphiboles, anthophyllite, chrysotile, and erionite), it was demonstrated that mesothelioma potency factors can be predicted based on DCC and biosolubility with a high level of accuracy (R=0.98, R<sup>2</sup>=0.96, p < 0.006). It was demonstrated that modeled mesothelioma potency correlates with relative potency for pleural instillation in Wistar rats, and correlates inversely with membranolytic toxicity index HC50. Mesothelioma potency was demonstrated to be negligible in all non-asbestiform sets.</div></div><div><h3>Conclusions</h3><div>The habit of amphibole particles is predictive of biological behavior that can be estimated from the dimensional data for the particles.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101908"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-13DOI: 10.1016/j.toxrep.2025.101912
Ragnar Thomsen , Tobias Melton Axelsen , Nicoline Løkken , Lisa Maria Gemmerli Krogh , Nanna Reiter , Brian Schou Rasmussen , Emilie Lund Laursen
Semisynthetic cannabinoids (SSCs) are compounds closely related to the major phytocannabinoids. SSCs have recently appeared as legal alternatives to Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive compound in the Cannabis plant. Δ9-THC has been consumed by humans for millennia and has low acute toxicity, but recent evidence indicates elevated toxicity from exposure to some SSCs. The present study describes two case reports with confirmed intoxication with a novel SSC, hexahydrocannabioctyl (HHC-C8). In the first case, a young male was found deeply unconscious and hospitalized. The clinical picture was mostly neurological with recurring seizures and coma. The patient was comatose for two days with a slow gradual improvement over the following two weeks. An HHC-C8 blood concentration of 72 ng/mL was determined in a sample taken at time of admission and the compound was also confirmed at a concentration of 6 % in a cannabis product of the same type and purchased at the same store. In the second case, a female was hospitalized after having slept for 14 hours and found in a minimally responsive state. The patient suffered pronounced somnolence and sedation for 3 days after which she gradually recovered. In a blood sample taken 40 hours after ingestion, HHC-C8 was detected at trace amounts along with two putative metabolites. The ingested product, which the patient had purchased at a web shop, was found to contain 7 % HHC-C8. The two cases demonstrate the toxic potential of widely available and often mislabeled cannabis products, the intake of which can lead to intoxications requiring extensive medical treatment.
{"title":"Prolonged sedation and unconsciousness after intoxication with the novel semisynthetic cannabinoid hexahydrocannabioctyl (HHC-C8): Two case descriptions","authors":"Ragnar Thomsen , Tobias Melton Axelsen , Nicoline Løkken , Lisa Maria Gemmerli Krogh , Nanna Reiter , Brian Schou Rasmussen , Emilie Lund Laursen","doi":"10.1016/j.toxrep.2025.101912","DOIUrl":"10.1016/j.toxrep.2025.101912","url":null,"abstract":"<div><div>Semisynthetic cannabinoids (SSCs) are compounds closely related to the major phytocannabinoids. SSCs have recently appeared as legal alternatives to Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC), the primary psychoactive compound in the <em>Cannabis</em> plant. Δ<sup>9</sup>-THC has been consumed by humans for millennia and has low acute toxicity, but recent evidence indicates elevated toxicity from exposure to some SSCs. The present study describes two case reports with confirmed intoxication with a novel SSC, hexahydrocannabioctyl (HHC-C8). In the first case, a young male was found deeply unconscious and hospitalized. The clinical picture was mostly neurological with recurring seizures and coma. The patient was comatose for two days with a slow gradual improvement over the following two weeks. An HHC-C8 blood concentration of 72 ng/mL was determined in a sample taken at time of admission and the compound was also confirmed at a concentration of 6 % in a cannabis product of the same type and purchased at the same store. In the second case, a female was hospitalized after having slept for 14 hours and found in a minimally responsive state. The patient suffered pronounced somnolence and sedation for 3 days after which she gradually recovered. In a blood sample taken 40 hours after ingestion, HHC-C8 was detected at trace amounts along with two putative metabolites. The ingested product, which the patient had purchased at a web shop, was found to contain 7 % HHC-C8. The two cases demonstrate the toxic potential of widely available and often mislabeled cannabis products, the intake of which can lead to intoxications requiring extensive medical treatment.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101912"},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-13DOI: 10.1016/j.toxrep.2025.101909
V.A. Alcántara-Mejía , A.A. Beltrán-Flores , R.A. Mateos-Nava , L. Álvarez-Barrera , I.U. Bahena-Ocampo , E. Santiago-Osorio , E. Bonilla-González , J.J. Rodríguez-Mercado
Vanadium (V) has garnered attention due to its pharmacological properties; however, its toxic effects have also been documented. Among the vanadium compounds that are found in the environment, vanadium trioxide (V2O3) has attracted interest because of its impact on biomolecules such as DNA, RNA, and proteins. However, its precise mechanism of action remains unclear, although it is suspected to be related to oxidative stress. Therefore, this study aimed to determine the mechanisms involved in DNA damage and the associated cellular response pathways. Primary cultures of human lymphocytes were exposed to 2, 4, 8, or 16 µg/mL V2O3. DNA damage due to oxidized bases was evaluated via a comet assay. The expression levels of sensor proteins (ATM and ATR) involved in DNA damage were determined via Western blotting, and the mRNA expression levels of metallothionein 1 (Mt-1) and genes involved in DNA repair (OGG1, APE1, XPB, XPD, MRE11, RAD50, Ku70, and Ku80) were estimated via RT-PCR and qPCR. The results showed that V2O3 is an oxidant that is responsible for DNA damage through oxidized bases, as demonstrated by increased DNA migration in the presence of the FPG enzyme. At the molecular level, V2O3 treatment also increased ATM protein expression. In terms of mRNA expression, the overexpression of Mt-1, OGG1, APE1, Ku70, and Ku80 was observed. This finding suggests that DNA damage is primarily repaired via two mechanisms: base excision repair (BER) and nonhomologous end joining (NHEJ). In conclusion, one mechanism of action of V2O3 involves the oxidation of nitrogenous bases in DNA, the activation of damage sensors (such as ATMs), and the overexpression of Mt-1 as part of the antioxidant response to mitigate the effects of V and facilitate DNA repair pathways (including BER and NHEJ).
{"title":"Oxidative damage to DNA, expression of Mt-1, and activation of repair mechanisms induced by vanadium trioxide in cultures of human lymphocytes","authors":"V.A. Alcántara-Mejía , A.A. Beltrán-Flores , R.A. Mateos-Nava , L. Álvarez-Barrera , I.U. Bahena-Ocampo , E. Santiago-Osorio , E. Bonilla-González , J.J. Rodríguez-Mercado","doi":"10.1016/j.toxrep.2025.101909","DOIUrl":"10.1016/j.toxrep.2025.101909","url":null,"abstract":"<div><div>Vanadium (V) has garnered attention due to its pharmacological properties; however, its toxic effects have also been documented. Among the vanadium compounds that are found in the environment, vanadium trioxide (V<sub>2</sub>O<sub>3</sub>) has attracted interest because of its impact on biomolecules such as DNA, RNA, and proteins. However, its precise mechanism of action remains unclear, although it is suspected to be related to oxidative stress. Therefore, this study aimed to determine the mechanisms involved in DNA damage and the associated cellular response pathways. Primary cultures of human lymphocytes were exposed to 2, 4, 8, or 16 µg/mL V<sub>2</sub>O<sub>3</sub>. DNA damage due to oxidized bases was evaluated via a comet assay. The expression levels of sensor proteins (ATM and ATR) involved in DNA damage were determined via Western blotting, and the mRNA expression levels of metallothionein 1 (<em>Mt-1</em>) and genes involved in DNA repair (<em>OGG1</em>, <em>APE1</em>, <em>XPB</em>, <em>XPD</em>, <em>MRE11</em>, <em>RAD50</em>, <em>Ku70</em>, and <em>Ku80</em>) were estimated via RT-PCR and qPCR. The results showed that V<sub>2</sub>O<sub>3</sub> is an oxidant that is responsible for DNA damage through oxidized bases, as demonstrated by increased DNA migration in the presence of the FPG enzyme. At the molecular level, V<sub>2</sub>O<sub>3</sub> treatment also increased ATM protein expression. In terms of mRNA expression, the overexpression of <em>Mt-1</em>, <em>OGG1</em>, <em>APE1</em>, <em>Ku70</em>, and <em>Ku80</em> was observed. This finding suggests that DNA damage is primarily repaired via two mechanisms: base excision repair (BER) and nonhomologous end joining (NHEJ). In conclusion, one mechanism of action of V<sub>2</sub>O<sub>3</sub> involves the oxidation of nitrogenous bases in DNA, the activation of damage sensors (such as ATMs), and the overexpression of Mt-1 as part of the antioxidant response to mitigate the effects of V and facilitate DNA repair pathways (including BER and NHEJ).</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101909"},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug residues have been detected in aquatic environments around the world and non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most used classes. Therefore, it is important to verify the physiological effects of these products on exposed non-target organisms such as fish. Through a meta-analytic review, we evaluated the effects of NSAIDs on oxidative stress biomarkers in fish. Overall, Diclofenac was the most frequently tested drug in the systematically selected studies while acute and hydric exposure types were the most prevalent among these studies. The meta-analysis revealed that (1) chronic and subchronic exposures to NSAIDs decreased catalase (CAT) activity, and acute exposure increased glutathione peroxidase (GPx) activity; (2) hydric exposure increased GPx activity; (3) exposure to low concentrations of NSAIDs increased GPx and superoxide dismutase (SOD) activity; (4) Paracetamol exposure increased GPx and SOD activity and lipid peroxidation levels, but reduced glutathione S-transferase (GST) activity; (5) Diclofenac exposure increased GPx activity. In conclusion, our results demonstrated that fish are sensitive to NSAIDs exposure presenting significant alterations in oxidative stress biomarkers, especially in the GPx enzyme. This enzyme exhibits strong potential as a biomarker of NSAIDs exposure in fish. Paracetamol stood out as the NSAID that altered the largest number of oxidative stress biomarkers, drawing attention to its risk to fish. In contrast, ibuprofen did not change the biomarkers evaluated. These data demonstrate the important impact of emerging contaminants such as NSAIDs on aquatic organisms and the need for strategies to mitigate these effects.
{"title":"Non-steroidal anti-inflammatory drugs and oxidative stress biomarkers in fish: a meta-analytic review","authors":"Luiz Henrique Zaniolo Justi , Juliana Ferreira Silva , Manuela Santos Santana , Henrique Aparecido Laureano , Meire Ellen Pereira , Cláudia Sirlene Oliveira , Izonete Cristina Guiloski","doi":"10.1016/j.toxrep.2025.101910","DOIUrl":"10.1016/j.toxrep.2025.101910","url":null,"abstract":"<div><div>Drug residues have been detected in aquatic environments around the world and non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most used classes. Therefore, it is important to verify the physiological effects of these products on exposed non-target organisms such as fish. Through a meta-analytic review, we evaluated the effects of NSAIDs on oxidative stress biomarkers in fish. Overall, Diclofenac was the most frequently tested drug in the systematically selected studies while acute and hydric exposure types were the most prevalent among these studies. The meta-analysis revealed that (1) chronic and subchronic exposures to NSAIDs decreased catalase (CAT) activity, and acute exposure increased glutathione peroxidase (GPx) activity; (2) hydric exposure increased GPx activity; (3) exposure to low concentrations of NSAIDs increased GPx and superoxide dismutase (SOD) activity; (4) Paracetamol exposure increased GPx and SOD activity and lipid peroxidation levels, but reduced glutathione S-transferase (GST) activity; (5) Diclofenac exposure increased GPx activity. In conclusion, our results demonstrated that fish are sensitive to NSAIDs exposure presenting significant alterations in oxidative stress biomarkers, especially in the GPx enzyme. This enzyme exhibits strong potential as a biomarker of NSAIDs exposure in fish. Paracetamol stood out as the NSAID that altered the largest number of oxidative stress biomarkers, drawing attention to its risk to fish. In contrast, ibuprofen did not change the biomarkers evaluated. These data demonstrate the important impact of emerging contaminants such as NSAIDs on aquatic organisms and the need for strategies to mitigate these effects.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101910"},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-13DOI: 10.1016/j.toxrep.2025.101905
Enyojo S. Okwute, Zakari Mohammed, David E. Arthur, Haruna B. Wayar, Joseph C. Akan
This study evaluates the concentrations of seventeen polycyclic aromatic hydrocarbons (PAHs) in soil and selected vegetable samples (onions, tomatoes, hot peppers, sweet peppers, and garden eggs) from Tiga agricultural locations in Kano State, Nigeria. Soil samples were collected from ten plots (depth profiles of 0–10 cm, 10–20 cm, and 20–30 cm) and combined at each depth to create composite samples. Additionally, 20 g of each vegetable were collected and divided into fruit, stem, and root components. Standard procedures were used for the extraction and clean-up of PAHs from both soil and vegetable samples, and instrumental analysis was conducted using SHIMADZU GC-MS (GC-17A). PAH levels in soil ranged from 1.20E-02 mg/kg to 3.80E-02 mg/kg, while vegetables showed concentrations from 1.00E-03 mg/kg to 8.90E-02 mg/kg. The 0–10 cm soil samples displayed higher PAH concentrations among all the depths studied, while the vegetables with the highest PAH concentration followed the trend: Onions > Sweet Pepper > Tomatoes > Hot Pepper > Garden Egg. Overall, total PAH concentrations in vegetables exceeded those in soil. Estimated daily PAH doses were below the Tolerable Daily Dose Limit set by FAO, indicating low health risks. Incremental lifetime cancer risk values also fell below US EPA acceptable levels (10E-06), suggesting negligible cancer risk while the hazard index was less than 1, implying no appreciable non-cancer health risks. PAH pollution was attributed to both petrogenic and pyrogenic sources. The findings of this study indicate that under the assessed conditions, the five vegetables evaluated from Tiga pose no significant risk and are considered safe for consumption.
{"title":"Human health risks of PAHs in soil and vegetables from Tiga, Kano State, Nigeria","authors":"Enyojo S. Okwute, Zakari Mohammed, David E. Arthur, Haruna B. Wayar, Joseph C. Akan","doi":"10.1016/j.toxrep.2025.101905","DOIUrl":"10.1016/j.toxrep.2025.101905","url":null,"abstract":"<div><div>This study evaluates the concentrations of seventeen polycyclic aromatic hydrocarbons (PAHs) in soil and selected vegetable samples (onions, tomatoes, hot peppers, sweet peppers, and garden eggs) from Tiga agricultural locations in Kano State, Nigeria. Soil samples were collected from ten plots (depth profiles of 0–10 cm, 10–20 cm, and 20–30 cm) and combined at each depth to create composite samples. Additionally, 20 g of each vegetable were collected and divided into fruit, stem, and root components. Standard procedures were used for the extraction and clean-up of PAHs from both soil and vegetable samples, and instrumental analysis was conducted using SHIMADZU GC-MS (GC-17A). PAH levels in soil ranged from 1.20E-02 mg/kg to 3.80E-02 mg/kg, while vegetables showed concentrations from 1.00E-03 mg/kg to 8.90E-02 mg/kg. The 0–10 cm soil samples displayed higher PAH concentrations among all the depths studied, while the vegetables with the highest PAH concentration followed the trend: Onions > Sweet Pepper > Tomatoes > Hot Pepper > Garden Egg. Overall, total PAH concentrations in vegetables exceeded those in soil. Estimated daily PAH doses were below the Tolerable Daily Dose Limit set by FAO, indicating low health risks. Incremental lifetime cancer risk values also fell below US EPA acceptable levels (10E-06), suggesting negligible cancer risk while the hazard index was less than 1, implying no appreciable non-cancer health risks. PAH pollution was attributed to both petrogenic and pyrogenic sources. The findings of this study indicate that under the assessed conditions, the five vegetables evaluated from Tiga pose no significant risk and are considered safe for consumption.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101905"},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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