Pub Date : 2025-01-10DOI: 10.1016/j.toxrep.2025.101900
R. Arulnangai , H. Asia Thabassoom , H. Vajiha Banu , K. Thirugnanasambandham , R. Ganesamoorthy
A naturally occurring pentacyclic triterpenoid, ursolic acid (UA) has attracted a lot of interest due to its various pharmacological characteristics and its medical uses. The goal of this thorough review is to present a thorough examination of the therapeutic benefits of UA, including its anti-inflammatory, antioxidant, anticancer, antibacterial, and metabolic-regulating properties. We go over its origins, pharmacological characteristics, and advantages in the treatment of several illnesses, including cancer, neurological disorders, metabolic disorders, and cardiovascular diseases. We further emphasize its potential to improve exercise capacity and its growing function as an exercise mimic. UA's therapeutic potential is thoroughly explained in this review, which highlights the compound's potential as a natural remedy for several illnesses.
{"title":"Recent developments on ursolic acid and its potential biological applications","authors":"R. Arulnangai , H. Asia Thabassoom , H. Vajiha Banu , K. Thirugnanasambandham , R. Ganesamoorthy","doi":"10.1016/j.toxrep.2025.101900","DOIUrl":"10.1016/j.toxrep.2025.101900","url":null,"abstract":"<div><div>A naturally occurring pentacyclic triterpenoid, ursolic acid (UA) has attracted a lot of interest due to its various pharmacological characteristics and its medical uses. The goal of this thorough review is to present a thorough examination of the therapeutic benefits of UA, including its anti-inflammatory, antioxidant, anticancer, antibacterial, and metabolic-regulating properties. We go over its origins, pharmacological characteristics, and advantages in the treatment of several illnesses, including cancer, neurological disorders, metabolic disorders, and cardiovascular diseases. We further emphasize its potential to improve exercise capacity and its growing function as an exercise mimic. UA's therapeutic potential is thoroughly explained in this review, which highlights the compound's potential as a natural remedy for several illnesses.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101900"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081013","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}
In the present study, we aim to identify a potential drug candidate that targets the Monocarboxylate Transporter-4 (MCT-4) protein. Syrosingopine (SRY) is a well-established inhibitor of lactate transport through MCT-4. We screened 2,11,192 potential leads through ZINC database, which were atleast 50 % structurally similar with SYR. After in-depth analysis, 900 molecules were shortlisted based on Lipinski's rule, optimal molecular weight, binding energy, hydrogen bonding, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties that render them viable MCT-4 inhibitors. The outcome underscored Brucine (BRU) as the most promising lead molecule within a cohort of ten potential compounds. BRU is a monoterpenoid indole alkaloid and is used in the regulation of high blood pressure and other comparatively benign cardiac ailments. As such, no reports is available emphasizing the efficacy of BRU on lactate transport or mammary gland carcinoma. BRU demonstrated strong affinity for the MCT-4 transporter's catalytic domain, forming significant hydrophobic and polar interactions with essential amino acids at the binding site. BRU demonstrated significant cytotoxicity and increased the extracellular lactate levels in MCF-7 cells. The findings strongly encouraged BRU's effectiveness, offering promising paths for subsequent investigations.
{"title":"Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4","authors":"Asma Khatoon Zaidi , Anurag Kumar , Rohit Kumar , Jyoti Singh , Sneha Yadav , Archana Bharti Sonkar , Dharmendra Kumar , Neeraj Kumar Shrivastava , Mohd Nazam Ansari , Abdulaziz S. Saeedan , Gaurav Kaithwas","doi":"10.1016/j.toxrep.2025.101902","DOIUrl":"10.1016/j.toxrep.2025.101902","url":null,"abstract":"<div><div>In the present study, we aim to identify a potential drug candidate that targets the Monocarboxylate Transporter-4 (MCT-4) protein. Syrosingopine (SRY) is a well-established inhibitor of lactate transport through MCT-4. We screened 2,11,192 potential leads through ZINC database, which were atleast 50 % structurally similar with SYR. After in-depth analysis, 900 molecules were shortlisted based on Lipinski's rule, optimal molecular weight, binding energy, hydrogen bonding, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties that render them viable MCT-4 inhibitors. The outcome underscored Brucine (BRU) as the most promising lead molecule within a cohort of ten potential compounds. BRU is a monoterpenoid indole alkaloid and is used in the regulation of high blood pressure and other comparatively benign cardiac ailments. As such, no reports is available emphasizing the efficacy of BRU on lactate transport or mammary gland carcinoma. BRU demonstrated strong affinity for the MCT-4 transporter's catalytic domain, forming significant hydrophobic and polar interactions with essential amino acids at the binding site. BRU demonstrated significant cytotoxicity and increased the extracellular lactate levels in MCF-7 cells. The findings strongly encouraged BRU's effectiveness, offering promising paths for subsequent investigations.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101902"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081016","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 : 2025-01-09DOI: 10.1016/j.toxrep.2025.101901
Silvia Muller de Moura Sarmento , Elizandra Gomes Schmitt , Laura Smolski dos Santos , Gênifer Erminda Schreiner , Rafael Tamborena Malheiros , Clóvis Klock , Charline Casanova Petry , Itamar Luís Gonçalves , Vanusa Manfredini
Vitamin D3 (VD3) is shown to be a biochemical and physiological modulator of the body. Debates about route of administration, prescribed dosage and serum levels have arisen, and thus the interaction of VD3 with the body in overdose. Using an experimental model of Wistar rats of both sexes, rats were subdivided into 5 groups, which represents a control group, and 4 groups with VD3 treatments (2.500, 7.000, 14.000 and 21.000 IU/kg/week) for one month. Thereafter biochemical, hormonal, inflammatory and histological analyses were performed. Regarding the biochemical findings, there was an increase in the levels of the AST in comparison of the control group with the treatments with higher doses (14.000 IU and 21.000 IU). Furthermore, changes in the inflammatory cytokine profile were identified at doses of 14,000 IU and 21,000 IU, with an increase in inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and a decrease in the anti-inflammatory IL-10. Histological evaluation of the liver tissue also revealed changes at the highest doses. Finally, in the evaluation of a murine physiological model, it showed that the supplementation of VD3 in overdoses there was an inflammatory exacerbation in the body, suggesting that the VD3 supplementation should be administered with caution, and takes into account physiological factors of the individual.
{"title":"Vitamin D supplementation: Biochemical and inflammatory effects in non-pathological Wistar rats","authors":"Silvia Muller de Moura Sarmento , Elizandra Gomes Schmitt , Laura Smolski dos Santos , Gênifer Erminda Schreiner , Rafael Tamborena Malheiros , Clóvis Klock , Charline Casanova Petry , Itamar Luís Gonçalves , Vanusa Manfredini","doi":"10.1016/j.toxrep.2025.101901","DOIUrl":"10.1016/j.toxrep.2025.101901","url":null,"abstract":"<div><div>Vitamin D<sub>3</sub> (VD<sub>3</sub>) is shown to be a biochemical and physiological modulator of the body. Debates about route of administration, prescribed dosage and serum levels have arisen, and thus the interaction of VD<sub>3</sub> with the body in overdose. Using an experimental model of Wistar rats of both sexes, rats were subdivided into 5 groups, which represents a control group, and 4 groups with VD<sub>3</sub> treatments (2.500, 7.000, 14.000 and 21.000 IU/kg/week) for one month. Thereafter biochemical, hormonal, inflammatory and histological analyses were performed. Regarding the biochemical findings, there was an increase in the levels of the AST in comparison of the control group with the treatments with higher doses (14.000 IU and 21.000 IU). Furthermore, changes in the inflammatory cytokine profile were identified at doses of 14,000 IU and 21,000 IU, with an increase in inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and a decrease in the anti-inflammatory IL-10. Histological evaluation of the liver tissue also revealed changes at the highest doses. Finally, in the evaluation of a murine physiological model, it showed that the supplementation of VD<sub>3</sub> in overdoses there was an inflammatory exacerbation in the body, suggesting that the VD<sub>3</sub> supplementation should be administered with caution, and takes into account physiological factors of the individual.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101901"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081112","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 : 2025-01-08DOI: 10.1016/j.toxrep.2025.101904
Mai Thi Thu Trinh , Truong Huynh Kim Thoa , Dang Thi Phuong Thao
Dimethyl sulfoxide (DMSO) is a polar aprotic solvent which is widely used in biological and medical studies and as a vehicle for pharmacological therapy. DMSO from 0.1 % to 0.5 %, particularly 0.3 % is commonly used as solvent to dissolve compounds when testing their effect on living cell, tissues including nerve cell. However, scientific data on the effects of DMSO on nervous system is limited. Here, we present our data of case study on investigation the effects of DMSO at 0.3 % concentration on nerve cell of Drosophila melanogaster model. We found that 0.3 % DMSO concentration had affected on the active zone and glutamate receptor. Notably, this study also revealed the synergistic effect of 0.3 % DMSO and loss function of dUCH (the homolog of Ubiquitin Carboxyl terminal Hydrolase -L1, UCH-L1 in D. melanogaster). This combination caused more serious abnormalities in synapse structure, particularly number of boutons on Neuromuscular Junction, NMJ. Furthermore, 0.3 % DMSO reduced the amount of ubiquitinylated protein aggregates in the indirect flight muscle of both normal and genectic defect fly model. Taken together, data in this sytudy indicated that 0.3 % DMSO caused the aberrant morphology of the synaptic structure and decreased the number of ubiquitinylated proteins in the indirect flight muscle of Drosophila. The data from the study contributed new evidence of the effects of DMSO on the nervous system. Signigicantly, this study revealed that DMSO affected on neuron cell at low concentration which widely used as pharmacological solvent.
{"title":"Neuronal effect of 0.3 % DMSO and the synergism between 0.3 % DMSO and loss function of UCH-L1 on Drosophila melanogaster model","authors":"Mai Thi Thu Trinh , Truong Huynh Kim Thoa , Dang Thi Phuong Thao","doi":"10.1016/j.toxrep.2025.101904","DOIUrl":"10.1016/j.toxrep.2025.101904","url":null,"abstract":"<div><div>Dimethyl sulfoxide (DMSO) is a polar aprotic solvent which is widely used in biological and medical studies and as a vehicle for pharmacological therapy. DMSO from 0.1 % to 0.5 %, particularly 0.3 % is commonly used as solvent to dissolve compounds when testing their effect on living cell, tissues including nerve cell. However, scientific data on the effects of DMSO on nervous system is limited. Here, we present our data of case study on investigation the effects of DMSO at 0.3 % concentration on nerve cell of <em>Drosophila melanogaster</em> model. We found that 0.3 % DMSO concentration had affected on the active zone and glutamate receptor. Notably, this study also revealed the synergistic effect of 0.3 % DMSO and loss function of dUCH (the homolog of Ubiquitin Carboxyl terminal Hydrolase -L1, UCH-L1 in <em>D. melanogaster</em>). This combination caused more serious abnormalities in synapse structure, particularly number of boutons on Neuromuscular Junction, NMJ. Furthermore, 0.3 % DMSO reduced the amount of ubiquitinylated protein aggregates in the indirect flight muscle of both normal and genectic defect fly model. Taken together, data in this sytudy indicated that 0.3 % DMSO caused the aberrant morphology of the synaptic structure and decreased the number of ubiquitinylated proteins in the indirect flight muscle of <em>Drosophila</em>. The data from the study contributed new evidence of the effects of DMSO on the nervous system. Signigicantly, this study revealed that DMSO affected on neuron cell at low concentration which widely used as pharmacological solvent.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101904"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080991","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 : 2025-01-08DOI: 10.1016/j.toxrep.2025.101903
Hafiza Monaza Batool , Madeeha Batool
Catecholamines and their metabolites play critical physiological roles in the human body. Paragangliomas and pheochromocytomas are rare adrenal tumors that significantly alter catecholamine metabolism, particularly the concentrations of metanephrine (MN) and normetanephrine (NMN). This study presents the development and validation of a rapid and straightforward analytical method using reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with a photodiode array (PDA) detector for quantifying MN and NMN in 24-h urine samples. Sample preparation involved adding 1 mL of urine to a tube containing the internal standard 3-methoxy-4-hydroxy benzylamine hydrochloride (MHBA) and a 2 g/L solution of 2-aminoethyl-diphenylborinate. After vortex mixing and centrifugation, ethyl acetate was used for extraction, and the organic layer was dried under nitrogen at 50–60 °C before reconstitution in the mobile phase. Chromatographic separation was achieved on an RP C-18 column with an isocratic flow of the mobile phase (sodium dihydrogen phosphate, citric acid monohydrate, acetonitrile, and sodium octyl sulfate). Detection was performed at 347 nm, with peak identification based on standard retention times. The method was validated for linearity (10–2000 ng/mL), recovery, sensitivity, precision, accuracy, selectivity, carryover, stability, and dilution effects. It showed a strong correlation coefficient (>0.99) and accuracy within ± 15 %. Inter- and intra-day precision confirmed the method reliability. This validated technique is suitable for clinical and research applications involving catecholamine metabolite screening.
{"title":"Optimization of HPLC method for metanephrine and normetanephrine detection in urine: Enhancing diagnostic precision for pheochromocytoma","authors":"Hafiza Monaza Batool , Madeeha Batool","doi":"10.1016/j.toxrep.2025.101903","DOIUrl":"10.1016/j.toxrep.2025.101903","url":null,"abstract":"<div><div>Catecholamines and their metabolites play critical physiological roles in the human body. Paragangliomas and pheochromocytomas are rare adrenal tumors that significantly alter catecholamine metabolism, particularly the concentrations of metanephrine (MN) and normetanephrine (NMN). This study presents the development and validation of a rapid and straightforward analytical method using reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with a photodiode array (PDA) detector for quantifying MN and NMN in 24-h urine samples. Sample preparation involved adding 1 mL of urine to a tube containing the internal standard 3-methoxy-4-hydroxy benzylamine hydrochloride (MHBA) and a 2 g/L solution of 2-aminoethyl-diphenylborinate. After vortex mixing and centrifugation, ethyl acetate was used for extraction, and the organic layer was dried under nitrogen at 50–60 °C before reconstitution in the mobile phase. Chromatographic separation was achieved on an RP C-18 column with an isocratic flow of the mobile phase (sodium dihydrogen phosphate, citric acid monohydrate, acetonitrile, and sodium octyl sulfate). Detection was performed at 347 nm, with peak identification based on standard retention times. The method was validated for linearity (10–2000 ng/mL), recovery, sensitivity, precision, accuracy, selectivity, carryover, stability, and dilution effects. It showed a strong correlation coefficient (>0.99) and accuracy within ± 15 %. Inter- and intra-day precision confirmed the method reliability. This validated technique is suitable for clinical and research applications involving catecholamine metabolite screening.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101903"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080993","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 : 2025-01-07DOI: 10.1016/j.toxrep.2024.101889
J. Serralabós-Ferré , I. Barceló-Carceller
Anticholinergic syndrome consists of neurological and systemic symptoms, including agitation, mydriasis and dryness that can be an adverse reaction to a number of medications, some of them as seemly harmless as cycloplegic mydriatic drops. We present the case of a 7-year-old previously healthy female child who presented to the emergency room with impaired neurological status, inability to recognize family members and incoherent speech, as well as facial flushing, mucosal dryness and bilateral mydriasis after having mistakenly received a high dose of mydriatic drops. She made a complete recovery without need for treatment and had no sequelae. It has been described that anticholinergic syndrome can be related to a number of mydriatic drops (such as cyclopentolate) as well as other medications, in adults, children and neonates. It is a clinical diagnosis and requires no etiological testing. Depending on the severity at presentation, it may be required to administer the antidote physostigmine.
{"title":"Anticholinergic syndrome due to mydriatic drops intoxication in a child: A case report","authors":"J. Serralabós-Ferré , I. Barceló-Carceller","doi":"10.1016/j.toxrep.2024.101889","DOIUrl":"10.1016/j.toxrep.2024.101889","url":null,"abstract":"<div><div>Anticholinergic syndrome consists of neurological and systemic symptoms, including agitation, mydriasis and dryness that can be an adverse reaction to a number of medications, some of them as seemly harmless as cycloplegic mydriatic drops. We present the case of a 7-year-old previously healthy female child who presented to the emergency room with impaired neurological status, inability to recognize family members and incoherent speech, as well as facial flushing, mucosal dryness and bilateral mydriasis after having mistakenly received a high dose of mydriatic drops. She made a complete recovery without need for treatment and had no sequelae. It has been described that anticholinergic syndrome can be related to a number of mydriatic drops (such as cyclopentolate) as well as other medications, in adults, children and neonates. It is a clinical diagnosis and requires no etiological testing. Depending on the severity at presentation, it may be required to administer the antidote physostigmine.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101889"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103504","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 : 2025-01-06DOI: 10.1016/j.toxrep.2025.101897
Ankita Mandal , Sharmistha Banerjee , Sumit Ghosh , Sima Biswas , Angshuman Bagchi , Parames C. Sil
Colitis is an inflammatory disorder of the gastrointestinal tract. A widely consumed dietary nutrient, α-ketoglutarate (α-KG) is known to play a crucial role in cellular metabolism and provide protection to intestinal epithelium under various pathophysiological conditions. In this study, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar rats. After 36 hours of TNBS administration, the rats were orally treated with a solution of α-KG at 1 g/kg body weight for 5 days. Development of colitis was confirmed by observable physical symptoms of repeated loose blood-mixed stool, apathy for food and weight loss. Macroscopic inspection revealed an inflamed colonic surface with ulcerations. Histopathological observations included alterations in crypts-structure and disruption in both epithelial and mucosal layers of colon in colitis induced rats. Colitis resulted in elevated levels of pro-inflammatory cytokines, ER stress-mediated cell death and intrinsic apoptosis pathway. The ameliorative effects of α-KG against TNBS-mediated toxicity were confirmed through molecular technics and docking analysis. Additionally, there were no instances of toxicity of α-KG. Therefore, α-KG can be considered as a valuable therapeutic agent for further comprehensive research.
{"title":"α-ketoglutarate ameliorates colitis through modulation of inflammation, ER stress, and apoptosis","authors":"Ankita Mandal , Sharmistha Banerjee , Sumit Ghosh , Sima Biswas , Angshuman Bagchi , Parames C. Sil","doi":"10.1016/j.toxrep.2025.101897","DOIUrl":"10.1016/j.toxrep.2025.101897","url":null,"abstract":"<div><div>Colitis is an inflammatory disorder of the gastrointestinal tract. A widely consumed dietary nutrient, α-ketoglutarate (α-KG) is known to play a crucial role in cellular metabolism and provide protection to intestinal epithelium under various pathophysiological conditions. In this study, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar rats. After 36 hours of TNBS administration, the rats were orally treated with a solution of α-KG at 1 g/kg body weight for 5 days. Development of colitis was confirmed by observable physical symptoms of repeated loose blood-mixed stool, apathy for food and weight loss. Macroscopic inspection revealed an inflamed colonic surface with ulcerations. Histopathological observations included alterations in crypts-structure and disruption in both epithelial and mucosal layers of colon in colitis induced rats. Colitis resulted in elevated levels of pro-inflammatory cytokines, ER stress-mediated cell death and intrinsic apoptosis pathway. The ameliorative effects of α-KG against TNBS-mediated toxicity were confirmed through molecular technics and docking analysis. Additionally, there were no instances of toxicity of α-KG. Therefore, α-KG can be considered as a valuable therapeutic agent for further comprehensive research.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101897"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068231","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 : 2025-01-06DOI: 10.1016/j.toxrep.2025.101896
Lucila Álvarez-Barrera , Rodrigo Aníbal Mateos-Nava , Keyla Nahomi Hernández-Córdova , Eduardo Lezama-Sánchez , Víctor Alan Alcántara-Mejía , Juan José Rodríguez-Mercado
The increased concentration of thallium (Tl) in the environment is a cause for concern because the entire population, including pregnant women, is exposed, and this metal crosses the placenta and reaches the conceptus during development. In biological models such as mice, some abnormalities and delays in ossification occur in the fetuses of mice administered Tl on day 7 of gestation, but exposure to environmental Tl is constant during fetal development; therefore, in this study, the effects of several administrations of TI during organogenesis on the external morphology, skeletal development and genotoxicity of fetuses were evaluated. Four groups of 10 pregnant mice were administered 5.28, 6.16, 7.4 or 9.25 mg/kg body weight Tl(I) acetate intraperitoneally during fetal organogenesis. Additionally, samples were taken from fetuses from pregnant mice treated with 5.28 and 6.16 mg/kg body weight to evaluate the transplacental genotoxicity. The results revealed that the 9.25 mg/kg body weight dose produced maternal and fetal toxicity, and all of the treatment groups presented relatively high percentages of fetuses with external abnormalities, reduced bone ossification, and an increased percentage of liver cells with structural chromosomal aberrations (SCAs) and micronuclei (MNs) in blood cells. These results show that Tl(I) acetate administered during organogenesis produces abnormalities, including a delay in ossification and transplacental genotoxicity, in mouse fetuses. These findings are important because Tl has negative effects on development and may affect the health of offspring in the future because it can damage genetic material.
{"title":"Transplacental and genotoxicity effects of thallium(I) during organogenesis in mice","authors":"Lucila Álvarez-Barrera , Rodrigo Aníbal Mateos-Nava , Keyla Nahomi Hernández-Córdova , Eduardo Lezama-Sánchez , Víctor Alan Alcántara-Mejía , Juan José Rodríguez-Mercado","doi":"10.1016/j.toxrep.2025.101896","DOIUrl":"10.1016/j.toxrep.2025.101896","url":null,"abstract":"<div><div>The increased concentration of thallium (Tl) in the environment is a cause for concern because the entire population, including pregnant women, is exposed, and this metal crosses the placenta and reaches the conceptus during development. In biological models such as mice, some abnormalities and delays in ossification occur in the fetuses of mice administered Tl on day 7 of gestation, but exposure to environmental Tl is constant during fetal development; therefore, in this study, the effects of several administrations of TI during organogenesis on the external morphology, skeletal development and genotoxicity of fetuses were evaluated. Four groups of 10 pregnant mice were administered 5.28, 6.16, 7.4 or 9.25 mg/kg body weight Tl(I) acetate intraperitoneally during fetal organogenesis. Additionally, samples were taken from fetuses from pregnant mice treated with 5.28 and 6.16 mg/kg body weight to evaluate the transplacental genotoxicity. The results revealed that the 9.25 mg/kg body weight dose produced maternal and fetal toxicity, and all of the treatment groups presented relatively high percentages of fetuses with external abnormalities, reduced bone ossification, and an increased percentage of liver cells with structural chromosomal aberrations (SCAs) and micronuclei (MNs) in blood cells. These results show that Tl(I) acetate administered during organogenesis produces abnormalities, including a delay in ossification and transplacental genotoxicity, in mouse fetuses. These findings are important because Tl has negative effects on development and may affect the health of offspring in the future because it can damage genetic material.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101896"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081025","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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