Toxicology Reports最新文献

{"title":"Prolonged sedation and unconsciousness after intoxication with the novel semisynthetic cannabinoid hexahydrocannabioctyl (HHC-C8): Two case descriptions","authors":"Ragnar Thomsen ,&nbsp;Tobias Melton Axelsen ,&nbsp;Nicoline Løkken ,&nbsp;Lisa Maria Gemmerli Krogh ,&nbsp;Nanna Reiter ,&nbsp;Brian Schou Rasmussen ,&nbsp;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 Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive compound in the <em>Cannabis</em> 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.</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}

{"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 ,&nbsp;A.A. Beltrán-Flores ,&nbsp;R.A. Mateos-Nava ,&nbsp;L. Álvarez-Barrera ,&nbsp;I.U. Bahena-Ocampo ,&nbsp;E. Santiago-Osorio ,&nbsp;E. Bonilla-González ,&nbsp;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 (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 (<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 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 <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 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).</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}

{"title":"Non-steroidal anti-inflammatory drugs and oxidative stress biomarkers in fish: a meta-analytic review","authors":"Luiz Henrique Zaniolo Justi ,&nbsp;Juliana Ferreira Silva ,&nbsp;Manuela Santos Santana ,&nbsp;Henrique Aparecido Laureano ,&nbsp;Meire Ellen Pereira ,&nbsp;Cláudia Sirlene Oliveira ,&nbsp;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}

{"title":"Human health risks of PAHs in soil and vegetables from Tiga, Kano State, Nigeria","authors":"Enyojo S. Okwute,&nbsp;Zakari Mohammed,&nbsp;David E. Arthur,&nbsp;Haruna B. Wayar,&nbsp;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 &gt; Sweet Pepper &gt; Tomatoes &gt; Hot Pepper &gt; 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}

{"title":"Recent developments on ursolic acid and its potential biological applications","authors":"R. Arulnangai ,&nbsp;H. Asia Thabassoom ,&nbsp;H. Vajiha Banu ,&nbsp;K. Thirugnanasambandham ,&nbsp;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}

{"title":"Corrigendum to “Saccharum officinarum molasses adversely alters reproductive functions in male Wistar rats” [Toxicol. Rep. 7 (2020) 345–352]","authors":"Eunice Ogunwole ,&nbsp;Olufadekemi T. Kunle-Alabi ,&nbsp;Opeyemi O. Akindele ,&nbsp;Yinusa Raji","doi":"10.1016/j.toxrep.2025.101893","DOIUrl":"10.1016/j.toxrep.2025.101893","url":null,"abstract":"","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101893"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103505","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}

{"title":"Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4","authors":"Asma Khatoon Zaidi ,&nbsp;Anurag Kumar ,&nbsp;Rohit Kumar ,&nbsp;Jyoti Singh ,&nbsp;Sneha Yadav ,&nbsp;Archana Bharti Sonkar ,&nbsp;Dharmendra Kumar ,&nbsp;Neeraj Kumar Shrivastava ,&nbsp;Mohd Nazam Ansari ,&nbsp;Abdulaziz S. Saeedan ,&nbsp;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}

{"title":"Vitamin D supplementation: Biochemical and inflammatory effects in non-pathological Wistar rats","authors":"Silvia Muller de Moura Sarmento ,&nbsp;Elizandra Gomes Schmitt ,&nbsp;Laura Smolski dos Santos ,&nbsp;Gênifer Erminda Schreiner ,&nbsp;Rafael Tamborena Malheiros ,&nbsp;Clóvis Klock ,&nbsp;Charline Casanova Petry ,&nbsp;Itamar Luís Gonçalves ,&nbsp;Vanusa Manfredini","doi":"10.1016/j.toxrep.2025.101901","DOIUrl":"10.1016/j.toxrep.2025.101901","url":null,"abstract":"<div><div>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.</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}

{"title":"Corrigendum to “From prescription to pollution: The ecological consequences of NSAIDs in aquatic ecosystems” [Toxicol. Rep. 13 (2024) 101775]","authors":"Vijaya Geetha B,&nbsp;Divya Lakshmi S,&nbsp;Vibha Murali","doi":"10.1016/j.toxrep.2025.101892","DOIUrl":"10.1016/j.toxrep.2025.101892","url":null,"abstract":"","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101892"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068151","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}

{"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 ,&nbsp;Truong Huynh Kim Thoa ,&nbsp;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}