Pub Date : 2025-12-01DOI: 10.1016/j.toxrep.2025.102178
Hon Chun, Tin Yat Anthony Chow
[This corrects the article DOI: 10.1016/j.toxrep.2025.102168.].
[这更正了文章DOI: 10.1016/j.toxrep.2025.102168.]。
{"title":"Corrigendum to \"A case series of hyperthermia crisis in cough mixture ingestion: Why early cooling save lives\" [Toxicol. Rep., 15 (2025) 102168].","authors":"Hon Chun, Tin Yat Anthony Chow","doi":"10.1016/j.toxrep.2025.102178","DOIUrl":"https://doi.org/10.1016/j.toxrep.2025.102178","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.toxrep.2025.102168.].</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"102178"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865354","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 : 2025-11-29DOI: 10.1016/j.toxrep.2025.102176
Julie Laval , Kirt R. Phipps , Sonia Brinet , Marie-Cécile Fournier , Benoit Douillard , Sa Pham , Alexandra Lobach , Severin Mueller , Pascale Fança-Berthon
Recent advances have led the development of turmeric formulations providing notable blood levels of curcuminoids following ingestion. However, there is a lack of clinical trials confirming the tolerability and safety of these formulations after repeated consumption by healthy subjects, as previous studies have primarily focused on efficacy and safety in subjects with health conditions. This randomised controlled trial assessed the gastrointestinal tolerance and safety of a novel turmeric extract formulation (TF) in healthy adults. Sixty subjects were assigned to either the TF group, receiving 1000 mg or placebo group (maltodextrin), once daily for 5 weeks. The study evaluated: gastrointestinal tolerance [including bloating, abdominal cramping, stomach noises, flatulence, frequency and consistency of stools and perception of Gastrointestinal Quality of Life (GIQLI)], a comprehensive analysis of haematology, clinical biochemistry and urinalysis parameters, vital signs, and a record of adverse events (AEs). No statistically significant differences were observed in gastrointestinal tolerance between the groups. Clinical parameters were not adversely affected by TF consumption, and the incidence and severity of AEs were similar in both groups. In conclusion, daily oral consumption of 1000 mg TF, thus exceeding the recommended 300 mg dose, was well tolerated and safe in healthy adults over the 5-week period.
{"title":"Safety assessment and gastrointestinal tolerance of a novel highly bioavailable turmeric extract formulation: A randomised, double-blind, placebo controlled clinical trial","authors":"Julie Laval , Kirt R. Phipps , Sonia Brinet , Marie-Cécile Fournier , Benoit Douillard , Sa Pham , Alexandra Lobach , Severin Mueller , Pascale Fança-Berthon","doi":"10.1016/j.toxrep.2025.102176","DOIUrl":"10.1016/j.toxrep.2025.102176","url":null,"abstract":"<div><div>Recent advances have led the development of turmeric formulations providing notable blood levels of curcuminoids following ingestion. However, there is a lack of clinical trials confirming the tolerability and safety of these formulations after repeated consumption by healthy subjects, as previous studies have primarily focused on efficacy and safety in subjects with health conditions. This randomised controlled trial assessed the gastrointestinal tolerance and safety of a novel turmeric extract formulation (TF) in healthy adults. Sixty subjects were assigned to either the TF group, receiving 1000 mg or placebo group (maltodextrin), once daily for 5 weeks. The study evaluated: gastrointestinal tolerance [including bloating, abdominal cramping, stomach noises, flatulence, frequency and consistency of stools and perception of Gastrointestinal Quality of Life (GIQLI)], a comprehensive analysis of haematology, clinical biochemistry and urinalysis parameters, vital signs, and a record of adverse events (AEs). No statistically significant differences were observed in gastrointestinal tolerance between the groups. Clinical parameters were not adversely affected by TF consumption, and the incidence and severity of AEs were similar in both groups. In conclusion, daily oral consumption of 1000 mg TF, thus exceeding the recommended 300 mg dose, was well tolerated and safe in healthy adults over the 5-week period.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102176"},"PeriodicalIF":0.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145698182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.toxrep.2025.102169
Anish Mahadeo , Theo K. Bammler , James MacDonald , Angela R. Zheng , Catherine K. Yeung , Jonathan Himmelfarb , Edward J. Kelly
Ochratoxin-A (OTA) is a ubiquitous mycotoxin contaminant in food products and a known nephrotoxin that is not currently regulated in the United States. OTA is hypothesized to be a potential environmental agent causing chronic kidney disease of unknown etiology (CKDu), however the mechanism of OTA toxicity in the human kidney remains elusive. This study aims to elucidate OTA-induced molecular toxicological pathways using primary human proximal tubule epithelial cells (PTECs). We demonstrated that exposure to OTA (10 μM) induces over 7000 differentially expressed genes, including key regulators of mitochondrial fission and fusion. This was confirmed at the cellular level by confocal microscopy, where a breakdown of the mitochondrial network was observed at 100 nM OTA. Crucially, low exposure (10 nM – 1 μM) was found to significantly inhibit basal mitochondrial oxidative phosphorylation as well as glycolysis through measurements of oxygen consumption rate and extracellular acidification, indicating reduced cellular energetics and mitochondrial toxicity. We demonstrate that OTA induces mitochondrial dysfunction and reduced ATP production in PTECs characteristic of renal disease progression. These findings provide insight into early proximal tubule damage induced by OTA which has been linked to pathophysiological changes involved in chronic kidney disease.
{"title":"Pervasive food contaminant ochratoxin‐A induces energy crisis: Mitochondrial dysfunction in human primary proximal tubule cells","authors":"Anish Mahadeo , Theo K. Bammler , James MacDonald , Angela R. Zheng , Catherine K. Yeung , Jonathan Himmelfarb , Edward J. Kelly","doi":"10.1016/j.toxrep.2025.102169","DOIUrl":"10.1016/j.toxrep.2025.102169","url":null,"abstract":"<div><div>Ochratoxin-A (OTA) is a ubiquitous mycotoxin contaminant in food products and a known nephrotoxin that is not currently regulated in the United States. OTA is hypothesized to be a potential environmental agent causing chronic kidney disease of unknown etiology (CKDu), however the mechanism of OTA toxicity in the human kidney remains elusive. This study aims to elucidate OTA-induced molecular toxicological pathways using primary human proximal tubule epithelial cells (PTECs). We demonstrated that exposure to OTA (10 μM) induces over 7000 differentially expressed genes, including key regulators of mitochondrial fission and fusion. This was confirmed at the cellular level by confocal microscopy, where a breakdown of the mitochondrial network was observed at 100 nM OTA. Crucially, low exposure (10 nM – 1 μM) was found to significantly inhibit basal mitochondrial oxidative phosphorylation as well as glycolysis through measurements of oxygen consumption rate and extracellular acidification, indicating reduced cellular energetics and mitochondrial toxicity. We demonstrate that OTA induces mitochondrial dysfunction and reduced ATP production in PTECs characteristic of renal disease progression. These findings provide insight into early proximal tubule damage induced by OTA which has been linked to pathophysiological changes involved in chronic kidney disease.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102169"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.toxrep.2025.102168
Hon Chun , Tin Yat Anthony Chow
Objective
Hyperthermia (core body temperature >40°C) associated with cough mixture ingestion has been reported in case studies. However, clinical data and consensus on treatment remain limited. This study aimed to identify associated factors, characterize clinical manifestations, and evaluate management approaches for hyperthermia following cough mixture ingestion.
Methods
A territory-wide retrospective case series was conducted using data from the Hong Kong Poison Information Centre (HKPIC) between 1 January 2013 and 31 December 2023. Patients aged > 18 years with cough mixture ingestion, hyperthermia (>40°C), and urine toxicology results were included. Cases with abusive stimulant co-ingestion were excluded.
Results
Of 434 recorded cough mixture exposures, 156 had urine toxicology results. After exclusions, 9 patients were included (100 % male; median age 37.1 ± 9.0 years). Mortality was 33.3 % (3/9). All cases occurred in daytime with ambient temperatures > 36°C. Promethazine and ephedrine were detected in all patients. Cooling methods were used in 55.6 % (5/9).
Conclusion
Promethazine/ ephedrine containing cough mixtures and high ambient temperatures may synergistically contribute to hyperthermia. Early recognition and aggressive cooling are critical to reduce mortality. Such cough mixtures should be restricted from being sold as over-the-counter medications.
{"title":"A case series of hyperthermia crisis in cough mixture ingestion: Why early cooling save lives","authors":"Hon Chun , Tin Yat Anthony Chow","doi":"10.1016/j.toxrep.2025.102168","DOIUrl":"10.1016/j.toxrep.2025.102168","url":null,"abstract":"<div><h3>Objective</h3><div>Hyperthermia (core body temperature >40°C) associated with cough mixture ingestion has been reported in case studies. However, clinical data and consensus on treatment remain limited. This study aimed to identify associated factors, characterize clinical manifestations, and evaluate management approaches for hyperthermia following cough mixture ingestion.</div></div><div><h3>Methods</h3><div>A territory-wide retrospective case series was conducted using data from the Hong Kong Poison Information Centre (HKPIC) between 1 January 2013 and 31 December 2023. Patients aged > 18 years with cough mixture ingestion, hyperthermia (>40°C), and urine toxicology results were included. Cases with abusive stimulant co-ingestion were excluded.</div></div><div><h3>Results</h3><div>Of 434 recorded cough mixture exposures, 156 had urine toxicology results. After exclusions, 9 patients were included (100 % male; median age 37.1 ± 9.0 years). Mortality was 33.3 % (3/9). All cases occurred in daytime with ambient temperatures > 36°C. Promethazine and ephedrine were detected in all patients. Cooling methods were used in 55.6 % (5/9).</div></div><div><h3>Conclusion</h3><div>Promethazine/ ephedrine containing cough mixtures and high ambient temperatures may synergistically contribute to hyperthermia. Early recognition and aggressive cooling are critical to reduce mortality. Such cough mixtures should be restricted from being sold as over-the-counter medications.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102168"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.toxrep.2025.102170
Yasser J.H. Alyassery , Ahsan F. Bairam , Carlos Medina Martin
Ischemia-reperfusion (IR) injury in the brain is a major cause of brain damage and neurotoxicity, particularly in patients with hypertension and diabetes, where oxidative stress and inflammation play critical roles. This study investigated the effects of telmisartan, ertugliflozin and omaveloxolone, on cerebral ischemia reperfusion IR-induced damage and neurotoxicity through modulation of the nuclear factor erythroid 2–related factor 2/ heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Forty-two rats were divided into seven groups, including controls and treatment groups that received the drugs before ischemia induction via bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. All three agents markedly enhanced Nrf2 immunoreactivity through immunohistochemical analysis and heme oxygenase-1 (HO-1) gene expression in brain tissues compared to controls. They also attenuated neurotoxic outcomes by reducing histopathological damage and lowering inflammatory mediators such as Nuclear Factor kappa-B (NF-κB), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Matrix Metalloproteinase-9 (MMP-9). A significant negative correlation was observed between Nrf2 activation and the severity of neurotoxicity inflammatory markers. In silico analysis revealed strong binding through highly negative docking scores of telmisartan and ertugliflozin to Nrf2 negative regulators Keap1 and GSK-3β, supported by stable molecular dynamics simulations, suggesting direct inhibition. In conclusion, omaveloxolone, telmisartan, and ertugliflozin alleviate ischemia-reperfusion induced neurotoxicity via potential Nrf2-mediated antioxidant and anti-inflammatory mechanisms, highlighting their potential preventive role in conditions predisposing to stroke.
脑缺血再灌注（IR）损伤是脑损伤和神经毒性的主要原因，特别是在高血压和糖尿病患者中，氧化应激和炎症起着关键作用。本研究探讨替米沙坦、厄图列净和奥马洛酮通过调节核因子-红细胞2相关因子2/血红素加氧酶-1 （Nrf2/HO-1）信号通路对ir诱导的脑缺血再灌注损伤和神经毒性的影响。42只大鼠分为7组，分别为对照组和治疗组，治疗组在双侧颈总动脉闭塞诱导缺血后再灌注给药。通过免疫组化分析和脑组织血红素加氧酶-1 （HO-1）基因表达，与对照组相比，这三种药物均显著增强Nrf2免疫反应性。它们还通过减少组织病理学损伤和降低炎症介质如核因子κ b （NF-κB）、肿瘤坏死因子α (TNF-α)、白细胞介素6 （IL-6）和基质金属蛋白酶9 （MMP-9）来减轻神经毒性结果。Nrf2激活与神经毒性炎症标志物的严重程度呈显著负相关。硅分析显示，通过高负对接分数，替米沙坦和埃图格列净与Nrf2负调节因子Keap1和GSK-3β强结合，稳定的分子动力学模拟支持，表明直接抑制。总之，奥马洛酮、替米沙坦和厄图列净通过潜在的nrf2介导的抗氧化和抗炎机制减轻缺血再灌注诱导的神经毒性，突出了它们在卒中易感疾病中的潜在预防作用。
{"title":"Attenuation of cerebral ischemia-reperfusion induced neurotoxicity by telmisartan, ertugliflozin, and omaveloxolone through Nrf2/HO-1 pathway modulation: In vivo and in silico insights","authors":"Yasser J.H. Alyassery , Ahsan F. Bairam , Carlos Medina Martin","doi":"10.1016/j.toxrep.2025.102170","DOIUrl":"10.1016/j.toxrep.2025.102170","url":null,"abstract":"<div><div>Ischemia-reperfusion (IR) injury in the brain is a major cause of brain damage and neurotoxicity, particularly in patients with hypertension and diabetes, where oxidative stress and inflammation play critical roles. This study investigated the effects of telmisartan, ertugliflozin and omaveloxolone, on cerebral ischemia reperfusion IR-induced damage and neurotoxicity through modulation of the nuclear factor erythroid 2–related factor 2/ heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Forty-two rats were divided into seven groups, including controls and treatment groups that received the drugs before ischemia induction via bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. All three agents markedly enhanced Nrf2 immunoreactivity through immunohistochemical analysis and heme oxygenase-1 (HO-1) gene expression in brain tissues compared to controls. They also attenuated neurotoxic outcomes by reducing histopathological damage and lowering inflammatory mediators such as Nuclear Factor kappa-B (NF-κB), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Matrix Metalloproteinase-9 (MMP-9). A significant negative correlation was observed between Nrf2 activation and the severity of neurotoxicity inflammatory markers. In silico analysis revealed strong binding through highly negative docking scores of telmisartan and ertugliflozin to Nrf2 negative regulators Keap1 and GSK-3β, supported by stable molecular dynamics simulations, suggesting direct inhibition. In conclusion, omaveloxolone, telmisartan, and ertugliflozin alleviate ischemia-reperfusion induced neurotoxicity via potential Nrf2-mediated antioxidant and anti-inflammatory mechanisms, highlighting their potential preventive role in conditions predisposing to stroke.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102170"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.toxrep.2025.102165
Anaïs M. Kipelo , Masi Jothilakshmi , Dhafer M.M. Al Salah , Georgette N. Ngweme , Emmanuel K. Atibu , Crispin Mulaji , Periyasamy Sivalingam , John W. Poté
This study examined the levels of trace elements in Brassica pekinensis Lour. collected from urban gardening sites (Cecomaf and Lutendele) in Kinshasa (Democratic Republic of the Congo) and associated potential human health risks for the consumer. The toxic metal concentrations in leaf samples were analysed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Atomic Absorption Spectrophotometer (AAS). Results showed that Cr, Cu, Cd, Pb, and Hg concentrations in samples from both sites exceeded the FAO/WHO maximum permissible limits, with Cecomaf displaying notably high levels of Cu (115.39 mg·kg⁻¹), Cd (2.95 mg·kg⁻¹), Pb (30.94 mg·kg⁻¹), and Hg (0.058 mg·kg⁻¹). Health risk assessments associated with the consumption of Brassica pekinensis L, based on Estimated Daily Intake (EDI), Target Hazard Quotient (THQ), and Hazard Index (HI), indices indicated that EDI values for Cd and Pb exceeded recommended limits in several samples, while THQ values exceeded 1 for most metals except As, suggesting potential non-carcinogenic risks. HI values ranged from 2.98 to 16.11 at Cecomaf and 4.85–12.15 at Lutendele, highlighting a high cumulative risk from individual and multi-metal exposure to consumers. Monte Carlo simulation further confirmed these findings by showing that a significant proportion of the exposed population exceeded the WHO safety thresholds for Cd, Pb, and Cu, thereby reinforcing the robustness of the deterministic risk estimates and illustrating the uncertainty associated with age, sex, and local consumption variability. Spearman correlation analysis revealed strong positive associations between Cr–As, Cr–Pb, and Cd–Hg, suggesting common anthropogenic sources or shared environmental pathways. Results of this study highlight the importance of continuous monitoring of trace elements in leafy vegetables for food safety evaluation, adopting stricter agricultural practices in policy making and management, and public health measures to mitigate long-term exposure risks to urban and peri-urban areas populations.
{"title":"Contamination level and dietary risk assessment of trace elements in Brassica pekinensis Lour. from gardening areas under tropical conditions","authors":"Anaïs M. Kipelo , Masi Jothilakshmi , Dhafer M.M. Al Salah , Georgette N. Ngweme , Emmanuel K. Atibu , Crispin Mulaji , Periyasamy Sivalingam , John W. Poté","doi":"10.1016/j.toxrep.2025.102165","DOIUrl":"10.1016/j.toxrep.2025.102165","url":null,"abstract":"<div><div>This study examined the levels of trace elements in <em>Brassica pekinensis Lour</em>. collected from urban gardening sites (Cecomaf and Lutendele) in Kinshasa (Democratic Republic of the Congo) and associated potential human health risks for the consumer. The toxic metal concentrations in leaf samples were analysed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Atomic Absorption Spectrophotometer (AAS). Results showed that Cr, Cu, Cd, Pb, and Hg concentrations in samples from both sites exceeded the FAO/WHO maximum permissible limits, with Cecomaf displaying notably high levels of Cu (115.39 mg·kg⁻¹), Cd (2.95 mg·kg⁻¹), Pb (30.94 mg·kg⁻¹), and Hg (0.058 mg·kg⁻¹). Health risk assessments associated with the consumption of <em>Brassica pekinensis</em> L, based on Estimated Daily Intake (EDI), Target Hazard Quotient (THQ), and Hazard Index (HI), indices indicated that EDI values for Cd and Pb exceeded recommended limits in several samples, while THQ values exceeded 1 for most metals except As, suggesting potential non-carcinogenic risks. HI values ranged from 2.98 to 16.11 at Cecomaf and 4.85–12.15 at Lutendele, highlighting a high cumulative risk from individual and multi-metal exposure to consumers. Monte Carlo simulation further confirmed these findings by showing that a significant proportion of the exposed population exceeded the WHO safety thresholds for Cd, Pb, and Cu, thereby reinforcing the robustness of the deterministic risk estimates and illustrating the uncertainty associated with age, sex, and local consumption variability. Spearman correlation analysis revealed strong positive associations between Cr–As, Cr–Pb, and Cd–Hg, suggesting common anthropogenic sources or shared environmental pathways. Results of this study highlight the importance of continuous monitoring of trace elements in leafy vegetables for food safety evaluation, adopting stricter agricultural practices in policy making and management, and public health measures to mitigate long-term exposure risks to urban and peri-urban areas populations.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102165"},"PeriodicalIF":0.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.toxrep.2025.102163
Lemessa B. Merga , Birhanu Mekassa , Bayissa Leta Danno , Lemma Mekonen Shumi
Mining activities are known sources of water pollution by Potentially Toxic Elements (PTEs), and threatening the health of humans and water ecosystem. This study aimed at evaluating the PTE concentrations and sources of PTEs enrichment in Tumet River, and associated human-ecological health risks in children and adults. The concentration of the studied PTEs (9 elements) in Tumet River water were quantified using Atomic Absorption Spectroscopic technique. The average values of the PTEs were found to be 0.02 ± 0.002–43.4 ± 1.4 mg/L, and 0.019 ± 0.001–39.7 ± 0.3 mg/L for dry and wet seasons, respectively. In both seasons the lowest and highest average values were observed for Cr and Fe, respectively. The average PTE concentrations exceeded drinking water (except for Zn and Cr) and ecological quality (except for Cr) guideline values in both dry and wet seasons. The risk assessment showed that the cumulative carcinogenic risk and non-carcinogenic risk results exceeded the USEPA threshold values for cancer (LCR > 1E-04) and non-cancer risks (HQ/HI > 1), indicating that the PTEs could pose both carcinogenic and non-carcinogenic health risks to adults and children from consumption or dermal exposure to water from Tumet River. Estimated Risk Quotient (RQ) values showed the probable ecological risks of the studied PTEs (RQ/HI > 1), in which Cu, Pb, Co and Ni can pose severe ecological risk to Tumet River ecosystem. The findings of this study highlight concerns about the health of the local community and the ecological quality of the river ecosystem due to PTEs pollution. To mitigate these issues, effective legal regulation of mining activities in the region is strongly recommended.
{"title":"Source apportionment, ecological and human health risk assessment of potentially toxic elements in Tumet River, Ethiopia","authors":"Lemessa B. Merga , Birhanu Mekassa , Bayissa Leta Danno , Lemma Mekonen Shumi","doi":"10.1016/j.toxrep.2025.102163","DOIUrl":"10.1016/j.toxrep.2025.102163","url":null,"abstract":"<div><div>Mining activities are known sources of water pollution by Potentially Toxic Elements (PTEs), and threatening the health of humans and water ecosystem. This study aimed at evaluating the PTE concentrations and sources of PTEs enrichment in Tumet River, and associated human-ecological health risks in children and adults. The concentration of the studied PTEs (9 elements) in Tumet River water were quantified using Atomic Absorption Spectroscopic technique. The average values of the PTEs were found to be 0.02 ± 0.002–43.4 ± 1.4 mg/L, and 0.019 ± 0.001–39.7 ± 0.3 mg/L for dry and wet seasons, respectively. In both seasons the lowest and highest average values were observed for Cr and Fe, respectively. The average PTE concentrations exceeded drinking water (except for Zn and Cr) and ecological quality (except for Cr) guideline values in both dry and wet seasons. The risk assessment showed that the cumulative carcinogenic risk and non-carcinogenic risk results exceeded the USEPA threshold values for cancer (LCR > 1E-04) and non-cancer risks (HQ/HI > 1), indicating that the PTEs could pose both carcinogenic and non-carcinogenic health risks to adults and children from consumption or dermal exposure to water from Tumet River. Estimated Risk Quotient (RQ) values showed the probable ecological risks of the studied PTEs (RQ/HI > 1), in which Cu, Pb, Co and Ni can pose severe ecological risk to Tumet River ecosystem. The findings of this study highlight concerns about the health of the local community and the ecological quality of the river ecosystem due to PTEs pollution. To mitigate these issues, effective legal regulation of mining activities in the region is strongly recommended.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102163"},"PeriodicalIF":0.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no available disease‑modifying therapy, and tramadol misuse has been increasingly associated with PD‑like neurotoxicity through oxidative stress, mitochondrial dysfunction, and apoptosis. This study investigated whether rosiglitazone (RSG), a PPARγ agonist, confers neuroprotection in tramadol-induced Parkinsonian rats by modulating PM20D1 gene expression, and whether its effects are enhanced in combination with levodopa–carbidopa. Fifty‑six male rats were randomized into seven groups: control, tramadol‑only, RSG (5/10/15 mg/kg) plus tramadol, levodopa–carbidopa plus tramadol, and RSG 5 mg/kg plus levodopa–carbidopa plus tramadol. Tramadol significantly impaired motor function and reduced dopamine compared to controls (serum: 189.0 ± 12.8 vs. 470.0 ± 21.2 pg/mL; brain: 54.8 ± 9.0 vs. 251.0 ± 43.6 pg/mL, p < 0.001), depleted antioxidants (SOD: 58.1 ± 8.5 vs. 155.0 ± 16.3 ng/mL; GSH: 6.9 ± 0.8 vs. 21.6 ± 2.6 µg/mL), and increased apoptosis (caspase‑3: 36.9 ± 3.6 vs. 10.0 ± 2.5 ng/mL). Relative to the tramadol‑only group, RSG dose‑dependently restored dopamine (up to 397.0 ± 23.1 pg/mL), normalized oxidative stress (MDA reduced to 1.5 ± 0.2 ng/mL), and upregulated PM20D1 gene expression (3.2 ± 0.5 fold) and BCL2 gene expression (3.2 ± 0.5 fold). The low-dose RSG plus levodopa–carbidopa combination achieved maximal behavioral recovery and dopamine restoration (1023.0 ± 248.0 pg/mL) compared to the tramadol-only group. These findings provide the first evidence that RSG confers neuroprotection against tramadol-induced Parkinsonism through PPARγ-mediated modulation of PM20D1 gene expression, highlighting a novel translational therapeutic axis with potential disease-modifying implications for PD.
{"title":"Modulation of PM20D1 expression by rosiglitazone confers neuroprotection in tramadol-induced Parkinsonian rats","authors":"Farah Hazim Hadi , Huda Jaber Waheed , Nawfal Abdulmonem Numan","doi":"10.1016/j.toxrep.2025.102164","DOIUrl":"10.1016/j.toxrep.2025.102164","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no available disease‑modifying therapy, and tramadol misuse has been increasingly associated with PD‑like neurotoxicity through oxidative stress, mitochondrial dysfunction, and apoptosis. This study investigated whether rosiglitazone (RSG), a PPARγ agonist, confers neuroprotection in tramadol-induced Parkinsonian rats by modulating PM20D1 gene expression, and whether its effects are enhanced in combination with levodopa–carbidopa. Fifty‑six male rats were randomized into seven groups: control, tramadol‑only, RSG (5/10/15 mg/kg) plus tramadol, levodopa–carbidopa plus tramadol, and RSG 5 mg/kg plus levodopa–carbidopa plus tramadol. Tramadol significantly impaired motor function and reduced dopamine compared to controls (serum: 189.0 ± 12.8 vs. 470.0 ± 21.2 pg/mL; brain: 54.8 ± 9.0 vs. 251.0 ± 43.6 pg/mL, p < 0.001), depleted antioxidants (SOD: 58.1 ± 8.5 vs. 155.0 ± 16.3 ng/mL; GSH: 6.9 ± 0.8 vs. 21.6 ± 2.6 µg/mL), and increased apoptosis (caspase‑3: 36.9 ± 3.6 vs. 10.0 ± 2.5 ng/mL). Relative to the tramadol‑only group, RSG dose‑dependently restored dopamine (up to 397.0 ± 23.1 pg/mL), normalized oxidative stress (MDA reduced to 1.5 ± 0.2 ng/mL), and upregulated PM20D1 gene expression (3.2 ± 0.5 fold) and BCL2 gene expression (3.2 ± 0.5 fold). The low-dose RSG plus levodopa–carbidopa combination achieved maximal behavioral recovery and dopamine restoration (1023.0 ± 248.0 pg/mL) compared to the tramadol-only group. These findings provide the first evidence that RSG confers neuroprotection against tramadol-induced Parkinsonism through PPARγ-mediated modulation of PM20D1 gene expression, highlighting a novel translational therapeutic axis with potential disease-modifying implications for PD.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102164"},"PeriodicalIF":0.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
One of the most serious neurological disorders is epilepsy. This study aimed to investigate the effects of baclofen, a GABA receptor agonist, on pain and seizure thresholds, as well as on oxidative damage in brain mitochondrial membranes of mice. Sixty male mice were divided into 10 groups. Control, baclofen (1, 5, and 10 mg/kg) with short-term exposure (1 day), long-term exposure (7 days), and withdrawal syndrome (eight days). The withdrawal syndrome was evaluated one day after the last dose of the drug. Hotplate and tail-flick tests were performed to assess pain threshold, and the rotarod was used to assess motor coordination. The seizure threshold and oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH), and the MTT assay, were investigated. The results showed that baclofen (10 mg/kg) in short-term and all doses (1, 5, and 10 mg/kg) in long-term increased the seizure threshold. Evaluation of motor function and coordination in mice revealed decreased motor activity. The effect of baclofen on oxidative damage showed that, in long-term exposure, it improved mitochondrial ROS, malondialdehyde, and GSH levels. Protein carbonyl and MTT tests did not show a significant difference. A GABAB receptor agonist causes a dose- and time-dependent increase in the seizure threshold. Baclofen could reduce oxidative damage by decreasing ROS levels and malondialdehyde formation, and increasing GSH content.
{"title":"The role of GABAergic receptors in acute, subacute, and withdrawal syndrome on pain and seizure thresholds in mice: A connection to mitochondrial function and oxidative stress in the brain","authors":"Roghayeh Jahani , Paria Pourbahram , Mohammad Seyedabadi , Fatemeh Nasiri , Hamidreza Mohammadi","doi":"10.1016/j.toxrep.2025.102158","DOIUrl":"10.1016/j.toxrep.2025.102158","url":null,"abstract":"<div><div>One of the most serious neurological disorders is epilepsy. This study aimed to investigate the effects of baclofen, a GABA receptor agonist, on pain and seizure thresholds, as well as on oxidative damage in brain mitochondrial membranes of mice. Sixty male mice were divided into 10 groups. Control, baclofen (1, 5, and 10 mg/kg) with short-term exposure (1 day), long-term exposure (7 days), and withdrawal syndrome (eight days). The withdrawal syndrome was evaluated one day after the last dose of the drug. Hotplate and tail-flick tests were performed to assess pain threshold, and the rotarod was used to assess motor coordination. The seizure threshold and oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH), and the MTT assay, were investigated. The results showed that baclofen (10 mg/kg) in short-term and all doses (1, 5, and 10 mg/kg) in long-term increased the seizure threshold. Evaluation of motor function and coordination in mice revealed decreased motor activity. The effect of baclofen on oxidative damage showed that, in long-term exposure, it improved mitochondrial ROS, malondialdehyde, and GSH levels. Protein carbonyl and MTT tests did not show a significant difference. A GABAB receptor agonist causes a dose- and time-dependent increase in the seizure threshold. Baclofen could reduce oxidative damage by decreasing ROS levels and malondialdehyde formation, and increasing GSH content.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102158"},"PeriodicalIF":0.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The escalating environmental presence of neuroactive pollutants such as Bisphenol-A (BPA) and aluminum chloride (AlCl₃) raises critical concerns regarding their long-term effects on cognitive health. This study presents a comparative neurotoxicity model using adult zebrafish (Danio rerio) exposed to a 21-day static immersion protocol with environmentally relevant doses (2 and 4 mg/L). Neurobehavioral changes were assessed using the novel tank diving test (NTDT) and a color-based T-maze test, combined with detailed histopathological scoring. BPA induced markedly stronger neurobehavioral and neuropathological effects than AlCl₃. BPA exposure caused dose-dependent reductions in swim velocity and distance travelled, heightened anxiety-like behavior, and cognitive inflexibility with reduced exploratory transitions and spatial learning. Histology revealed extensive vacuolation, neuronal pyknosis, and perineural congestion in the telencephalic and diencephalic regions, confirming widespread neurodegeneration. In contrast, AlCl₃ produced moderate impairments, with neuropathology primarily confined to the cerebellum and thalamus. These differential effects suggest distinct mechanisms: BPA may disrupt synaptic plasticity and hypothalamic–pituitary–interrenal (HPI) axis signaling, whereas AlCl₃ likely involves mitochondrial dysfunction and tauopathy. By integrating behavioral phenotyping with region-specific neuropathology, this model highlights the translational relevance of adult zebrafish for regulatory toxicology and human health risk assessment of aquatic neurotoxicants.
{"title":"Comparative neurotoxicity of Bisphenol-A and aluminum chloride in adult zebrafish: Behavioral disruption and region-specific neuropathology under chronic exposure","authors":"Logeshwari B , Srikanth Jeyabalan , Gayathri Veeraraghavan , Krishnaraj Kaliaperumal , Chetan Ashok , Naveen Kumar Rajasekaran , Ling Shing Wong , Vetriselvan Subramaniyan , Mahendran Sekar","doi":"10.1016/j.toxrep.2025.102161","DOIUrl":"10.1016/j.toxrep.2025.102161","url":null,"abstract":"<div><div>The escalating environmental presence of neuroactive pollutants such as Bisphenol-A (BPA) and aluminum chloride (AlCl₃) raises critical concerns regarding their long-term effects on cognitive health. This study presents a comparative neurotoxicity model using adult zebrafish (<em>Danio rerio</em>) exposed to a 21-day static immersion protocol with environmentally relevant doses (2 and 4 mg/L). Neurobehavioral changes were assessed using the novel tank diving test (NTDT) and a color-based T-maze test, combined with detailed histopathological scoring. BPA induced markedly stronger neurobehavioral and neuropathological effects than AlCl₃. BPA exposure caused dose-dependent reductions in swim velocity and distance travelled, heightened anxiety-like behavior, and cognitive inflexibility with reduced exploratory transitions and spatial learning. Histology revealed extensive vacuolation, neuronal pyknosis, and perineural congestion in the telencephalic and diencephalic regions, confirming widespread neurodegeneration. In contrast, AlCl₃ produced moderate impairments, with neuropathology primarily confined to the cerebellum and thalamus. These differential effects suggest distinct mechanisms: BPA may disrupt synaptic plasticity and hypothalamic–pituitary–interrenal (HPI) axis signaling, whereas AlCl₃ likely involves mitochondrial dysfunction and tauopathy. By integrating behavioral phenotyping with region-specific neuropathology, this model highlights the translational relevance of adult zebrafish for regulatory toxicology and human health risk assessment of aquatic neurotoxicants.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102161"},"PeriodicalIF":0.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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