Toxicology Reports最新文献

{"title":"Unveiling melatonin’s multifaceted actions against ferroptotic neurotoxicity in ischemic stroke","authors":"Soraya Boonmag ,&nbsp;Russel J. Reiter ,&nbsp;Piyarat Govitrapong","doi":"10.1016/j.toxrep.2026.102219","DOIUrl":"10.1016/j.toxrep.2026.102219","url":null,"abstract":"<div><div>Ferroptosis, an iron-mediated form of programmed cell death, is increasingly recognized for its role in neurodegenerative diseases, with relevance to ischemic stroke, a condition that creates a permissive environment for this process. The prevalence of ischemic stroke is steadily increasing, with its mortality rates rising startlingly in recent years. The urgency of timely intervention is of utmost importance, as failure to treat patients within the narrow therapeutic window often results in severe neurological damage, including severe paralysis or mortality. The pathology of ischemic stroke has been investigated to identify the underlying mechanism and determine efficient therapeutic strategies. Melatonin, a functionally versatile natural indoleamine, has shown promise in deferring neurodegenerative processes, including those associated with stroke. Melatonin exerts pleiotropic biological roles, including being a potent antioxidant, anti-inflammatory, iron chelator, neuroprotector, promoter of neurogenesis, and immune modulator. Recent studies on melatonin have also identified its efficacy in mitigating key events of ferroptosis, introducing it as an anti-ferroptosis agent. Herein, we highlight the prevailing concept of the pathophysiology of ischemic stroke, with emphasis on the emerging significance of ferroptotic neurotoxicity. Furthermore, we discussed recent research on the application of melatonin as a remedial intervention for ischemic stroke associated with ferroptosis.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102219"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173135","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}

{"title":"Phytochemical composition and anti-Alzheimer potential of medicinal plants from Central and West Africa: Systematic review","authors":"Protais Mukunzi ,&nbsp;Ben Shalom Byishimo ,&nbsp;Ekom Monday Etukudo ,&nbsp;Hyppolyte Iradukunda ,&nbsp;Darius Benimana ,&nbsp;Ibe Michael Usman ,&nbsp;Augustin Oviosun ,&nbsp;Comfort Ojochenemi Usman ,&nbsp;David Ikwuka ,&nbsp;Wusa Makena ,&nbsp;Victor Bassey Archibong","doi":"10.1016/j.toxrep.2026.102205","DOIUrl":"10.1016/j.toxrep.2026.102205","url":null,"abstract":"<div><div>In recent time, the use of medicinal plants in the management of human disease conditions has gained immense attention. The aim of the present review was to explore the phytochemical composition and anti-Alzheimer potential of medicinal plants from Central and West Africa. A structured systematic approach was used to conduct the present systematic review of articles. Scopus, PubMed, and Web of Science were searched using the following search terms combined by Boolean operators: (“Alzheimer’s disease” OR “Neurodegenerative disease” OR \"Nervous system diseases\") AND (“Extract” OR \"herbs\" OR “Plant”) AND (“West Africa” OR “Central Africa” OR “Africa”) on the 6th of July 2024 without any filters. Following the conclusion of the title, abstract, and full text screening, only 13 articles were included. Most of the included studies (10/13, 77 %) were conducted between 2014 and 2024. Geographically, 9 (69 %) studies were conducted in Nigeria. Plants identified in the present study include: <em>Solanum macrocarpon</em>, <em>Solanum nigru, Pteleopsis suberosa, Macrosphyra longistyl, Beta vulgaris, Persea americana, Syzygium aromaticum, Citrullus lanatus, Cucumeropsis mannii, Lagenaria siceraria, Achyranthes aspera Linn., Tithonia diversifolia.</em> These plants were found to contain Luteolin, Catechin, Decanoic acid methyl ester, 11,14-Eicosadienoic acid methyl ester, Caffeic acid, Syringic acid, Azelaic acid. The plant-derived phytochemicals were reported to modulate critical Alzheimer’s disease (AD) pathways, notably oxidative stress, acetylcholinesterase (AChE) inhibition, and neuroinflammation. In conclusion, Central and West African medicinal plants represent a rich reservoir of multifunctional neuroprotective metabolites capable of targeting diverse AD pathways.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102205"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977241","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}

{"title":"Human fluoroacetate poisoning: A case series of 36 patients in Vietnam","authors":"Nguyen Dang Duc ,&nbsp;Lam Nguyen Hong Anh ,&nbsp;Lam Nguyen Hong Khanh ,&nbsp;Nguyen Dang Bach","doi":"10.1016/j.toxrep.2025.102189","DOIUrl":"10.1016/j.toxrep.2025.102189","url":null,"abstract":"<div><div>Fluoroacetate poisoning is a rare but potentially lethal condition. We retrospectively reviewed 36 consecutive patients (27 males and 9 females) with confirmed poisoning treated at the Poison Control Center, Bach Mai Hospital, Hanoi, Vietnam, from June 2023 to December 2024. The mean age was 35.4 ± 12.6 years. The median time from ingestion to hospital admission was 3.5 h. On admission, 69.4 % of patients were asymptomatic, 22.2 % had seizures, and 8.3 % presented with altered consciousness. The mean Glasgow Coma Scale (GCS) score was 13.9 ± 2.0 (range 5–15). Median serum creatinine and creatine kinase (CK) levels were 72 µmol/L and 155 U/L, respectively; 16.7 % of patients had CK &gt; 1000 U/L. Median ionized calcium was 1.015 mmol/L, and 19.4 % had serum lactate ≥ 2 mmol/L. Gastric lavage and activated charcoal were administered in 44.4 % and 36.1 % of cases, respectively. Six patients (16.7 %) required intensive care unit (ICU) admission, and no deaths occurred. Overall, most patients presented early with mild manifestations and had favorable short-term outcomes under supportive management.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102189"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791811","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}

{"title":"Evaluation of the effects of dimethyl fumarate on transforming growth factor beta levels in the liver of rats with bile duct ligation-induced cholestasis","authors":"Hannaneh Vossoughi ,&nbsp;Pejman Mortazavi ,&nbsp;Mahsa Ale-Ebrahim ,&nbsp;Razieh Hosseini","doi":"10.1016/j.toxrep.2025.102115","DOIUrl":"10.1016/j.toxrep.2025.102115","url":null,"abstract":"<div><h3>Background</h3><div>Cholestasis is a reduction or cessation of bile flow in the biliary system, which can be life-threatening. Dimethyl Fumarate could induce anti-inflammatory and antioxidant effects in the body.</div></div><div><h3>Objective</h3><div>This investigation focused on assessing the impact of Dimethyl Fumarate on liver levels of transforming growth factor beta (TGF-β) to mitigate biochemical, histopathological, and immunohistochemical alterations in cholestasis-induced rat models.</div></div><div><h3>Methods</h3><div>Forty male adult Wistar rats were divided into eight groups (healthy control treated with distilled water, healthy rats treated with 50, 100, and 200 mg/kg of Dimethyl Fumarate, bile duct ligation (BDL), and experiment BDL groups were treated with 50, 100, and 200 mg/kg of Dimethyl Fumarate). After the gavage treatment period of 45 days, the rats were anesthetized and underwent blood sampling. Liver damage was assessed by measuring hepatic marker enzymes (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin), histopathological (lesion assessment), and immunohistochemical (TGF-β expression level) observation.</div></div><div><h3>Results</h3><div>The findings demonstrated that administration of varying doses of Dimethyl Fumarate via gavage led to a statistically significant reduction in serum concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin (<em>P</em> &lt; 0.05). The optimal dosage identified was 200 mg/kg of Dimethyl Fumarate. Furthermore, the data indicated that gavage treatment with Dimethyl Fumarate significantly attenuated TGF-β expression level and mitigated hepatic damage (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>This strategy may reduce inflammation, cholestasis, and fibrosis outcomes, attributed to its anti-inflammatory and antioxidant properties. Nonetheless, further research is necessary to substantiate these findings.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102115"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889040","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}

{"title":"Toxic metals and bioelements: Combined oxidative stress effects on liver injury and thyroid hormone disruption in subjects from different areas of Erbil province","authors":"Mahdi Yassin Ahmed,&nbsp;Kamaran Abdoulrahman","doi":"10.1016/j.toxrep.2025.102078","DOIUrl":"10.1016/j.toxrep.2025.102078","url":null,"abstract":"<div><div>In Iraq, particularly in Erbil city and Gwer road are deemed environmentally disadvantaged because of industrial pollutants and refinery activities. This study conducted 143 subjects from rural, urban, and industrial areas. The sera of subjects were taken for the analysis. The toxic metals and bioelements were assessed using ICP-MS, the oxidative stress parameters were determined via ELISA. For estimation of liver test biomarkers Kenza was used, and thyroid hormones were measured by Cobas. While their relationships were statistically analyzed. The results indicated that metals concentrations were markedly significantly increased in industrial areas, particularly for Fe 599.1 (723.9) μg/L and Mn 7.534 ± 8.793 μg/L. The median level of Cu 4082 (2824) μg/L in urban subjects is significantly lower than those of other areas. Markers for oxidative stress revealed considerably higher MDA in urban participants 1917 (1085) pg/mL, while SOD and CP exhibited significantly lower level in urban and industrial participants P-value (0.0001 and &lt;0.0001) respectively. The liver tests revealed elevated ALT in urban and industrial participants, 29.06 ± 1.723 IU/L and 21.94 ± 1.162 IU/L, respectively. The ALP levels were significantly elevated in industrial participants (P-value &lt;0.0001). The study found that industrial workers had significantly higher levels of TSH 2.209 ± 0.1032 μIU/L and low levels of T3 1.765 ± 0.0227 nmol/l compared to the rural individuals. Fe had positive correlations with ONOO^-. and TSH (r = 0.2221, r = 0.2452). Furthermore, Cu showed positively correlated with Cp (r = 0.2967; p = 0.0068), AST (r = 0.2417; p = 0.0268) and ALB (r = 0.2187; p = 0.0457). This study shows that increased levels of hazardous metals and bioelements in industrial and urban areas cause oxidative stress, which has a significant impact on public health and causes a number of health problems, including liver injury and thyroid dysfunction.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102078"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489873","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}

{"title":"Health impacts and risk assessment of PM2.5 and PM10 at Suburban Site in Pathum Thani, Thailand","authors":"Dussadee Rattanaphra ,&nbsp;Sittinun Tawkaew ,&nbsp;Wilasinee Kingkam ,&nbsp;Sasikarn Nuchdang ,&nbsp;Kittiwan Kitpakornsanti ,&nbsp;Unchalee Suwanmanee","doi":"10.1016/j.toxrep.2025.102109","DOIUrl":"10.1016/j.toxrep.2025.102109","url":null,"abstract":"<div><div>The aim of this study was to evaluate the carcinogenic and non-carcinogenic health risks associated with heavy metals in PM₂.₅ and PM₁₀ through inhalation exposure among children and adults during both the summer and wet seasons in the Pathum Thani Province, Thailand. PM2.5 and PM10 samples were collected using a Tisch TE-Wilbur sampler, and elemental concentrations were analyzed using Proton-Induced X-Ray Emission (PIXE). Microsoft Excel was employed to determine the statistical values of PM₂.₅ and PM₁₀ concentrations, the concentrations of twelve elements, including Si, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Zn, Ni, and Cu. The enrichment factor (EF), as well as health risk assessment indicators, including target hazard quotient (THQ), hazard index (HI), and carcinogenic risk (CR), were evaluated. The results showed that EF values for Zn, Ni, and Cu ranged from 10 to 100, indicating contributions from anthropogenic sources. Cr exhibited the highest EF values, ranging from 51 to 111, suggesting significant influence from industrial activities and traffic emissions. The mean PM₁₀ concentration (86.0504 µg/m³) during the wet season exceeded the WHO and EU standards but remained below the Thailand standard and the U.S. EPA limit. In contrast, the mean PM₂.₅ concentration (77.5143 µg/m³) during the same period exceeded all referenced standards. The calculated HI values were from 0.0459 to 0.1090 for adults and 0.3285–0.7811 for children. The CR values in PM₂.₅ ranged from 5.0884 × 10⁻⁸ to 7.9544 × 10⁻⁶ for adults and from 5.9364 × 10⁻⁸ to 9.2802 × 10⁻⁶ for children. For PM₁₀, the CR values ranged from 5.1865 × 10⁻⁸ to 1.0412 × 10⁻⁵ for adults and from 6.0509 × 10⁻⁸ to 1.2148 × 10⁻⁵ for children. Although both carcinogenic and non-carcinogenic risks were within acceptable limits, higher risk values were observed in children compared to adults. Therefore, targeted and effective air pollution control policies are recommended, with a particular emphasis on protecting children’s health and strengthening evidence-based air quality management strategies.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102109"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810509","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}

{"title":"British anti-Lewisite (BAL) reduces the severity of systemic and local responses of the eye after exposure to the chemical warfare agent surrogate for Lewisite, phenylarsine oxide (PAO)","authors":"Sarbani Hazra ,&nbsp;Aditya Konar ,&nbsp;Robb Welty ,&nbsp;Uday B. Kompella","doi":"10.1016/j.toxrep.2025.102153","DOIUrl":"10.1016/j.toxrep.2025.102153","url":null,"abstract":"<div><div>Arsenical ocular toxicity is acute, painful, and aggressive. Although British anti-Lewisite (BAL) is an approved therapy for systemic arsenical toxicity, remedial measure for ocular exposure of arsenicals is still an unmet need. This study evaluated the efficacy of BAL as topical drop for ameliorating the pathogenesis incited by phenylarsine oxide (PAO, surrogate for lewisite), a chemical warfare agent. The binding of BAL to arsenic and calcium and zinc, two essential cellular minerals was determined using Isothermal Titration Calorimetry (ITC). Ex vivo, mouse corneas were tested with various concentrations of BAL (0.1 %, 1 %, and 5 %). Injury was induced ex vivo using PAO, 25 µg/5 µL, and rescue was evaluated with 1 % BAL. In-vivo, injury to mouse cornea was induced with PAO 100 µg/5 µL and rescue was evaluated by 1 % BAL. All eyes were assessed for physical symptoms by examination under slit lamp biomicroscope, anterior segment optical coherence tomography (AS-OCT), corneal thickness, and histopathological changes. BAL bonded strongly with arsenic but negligibly with calcium and zinc. Ex-vivo cornea, response with 1 % BAL was graded superior to higher concentration. One of eight mice with PAO injury survived versus all survivals in the PAO+BAL group after injury. Topical use of BAL mitigated the exacerbated ocular response exhibited by PAO injury. Histology revealed better preservation of retinal architecture in BAL treated mice. 1 % BAL alleviates PAO induced fatality in mice. The rescue in the posterior segment pathogenesis was remarkable. BAL is a promising decontaminant for ocular arsenical exposure and warrants further investigation.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102153"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525378","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}

{"title":"Collateral damage: Cardiovascular and respiratory implications of tear gas deployment during peaceful protest","authors":"Konstantine Chakhunashvili ,&nbsp;Gela Gunashvili ,&nbsp;Nino Jobava ,&nbsp;George Chakhunashvili ,&nbsp;Davit G. Chakhunashvili","doi":"10.1016/j.toxrep.2025.102166","DOIUrl":"10.1016/j.toxrep.2025.102166","url":null,"abstract":"<div><h3>Background</h3><div>In December 2024, large-scale protests in front of Georgia’s Parliament were met with crowd-control measures involving the widespread use of tear gas and pepper spray, mixed with water. This study examined whether protest participants exposed to these agents exhibited electrocardiographic, capillaroscopic, or hematologic abnormalities, and explored associations with allergy status, mask use, and attendance frequency.</div></div><div><h3>Methods</h3><div>An observational case-control study was conducted from January 9 to March 1, 2025. Of 347 protest participants surveyed, 69 underwent clinical evaluation. A control group of 31 unexposed individuals was recruited. Participants received ECGs, capillaroscopy, complete blood count (CBC), and coagulogram testing. Data were analyzed using chi-square tests, eta coefficients, and t-tests (p &lt; 0.05).</div></div><div><h3>Results</h3><div>ECG abnormalities—including P-wave (p &lt; 0.001), QRS complex (p = 0.035), and T-wave (p = 0.012) changes—were significantly more frequent in the exposed group. Right bundle branch block and T-wave inversions were particularly notable. Capillaroscopy showed more non-specific and sclerodermal abnormalities in the exposed group, though not statistically significant. Allergy status was linked to higher symptom burden, while mask use and attendance frequency were not predictive. Laboratory parameters were largely normal. Two respiratory cases—hypersensitivity pneumonitis and unresolved pneumonia—were clinically linked to exposure.</div></div><div><h3>Conclusion</h3><div>Exposure to CS gas was associated with significant ECG changes, indicating potential cardiopulmonary effects. Clinical patterns and rare respiratory cases warrant re-evaluation of chemical agent use, improved oversight, and long-term studies to assess chronic health risks in exposed populations.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102166"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620694","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}

{"title":"In vivo genotoxicity of Chios mastic gum in rodent bone marrow micronucleus test","authors":"Eirini-Christina Psarou ,&nbsp;Aikaterini Termentzi ,&nbsp;Katerina Kyriakopoulou ,&nbsp;Pelagia Anastasiadou ,&nbsp;Marios Meidanis ,&nbsp;Nikolas Fokialakis ,&nbsp;Kyriaki Machera","doi":"10.1016/j.toxrep.2025.102155","DOIUrl":"10.1016/j.toxrep.2025.102155","url":null,"abstract":"<div><div>Chios mastic gum (CMG) exhibits several pharmacological activities that have been confirmed by numerous studies. These include antibacterial, anti-inflammatory, hypolipidemic, hypoglycemic, antiatheromatic, and benefits for against gastrointestinal disorders. However, studies focusing on CMG’s safety are limited. The aim of the present study is to evaluate the genotoxicity of CMG using the limit test on the mammalian erythrocyte micronucleus assay, in male Wistar rats. CMG was administered by gavage to 5 rats at 2000 mg/kg bw for 3 days, while 5 rats received the vehicle and 5 rats received cyclophosphamide (positive control). Satellite groups of 3 rats were included for the negative control and CMG-treated groups to collect plasma and bone marrow for the chemical analyses. All rats were observed for mortality and clinical signs of toxicity during the dosing period. Rats were euthanatized 20 h after the last treatment, necropsied, and bone marrow was collected for smear preparation. No mortality, clinical signs of toxicity, gross organ pathology, or body weight changes were observed in CMG-treated rats compared to the negative control group. No statistically significant alteration of polychromatic erythrocytes (PCE) and the per-thousand incidences of micronucleated PCE in the bone marrow of CMG-treated rats were observed. Bone marrow exposure to CMG was unambiguously confirmed by the detection of the characteristic CMG triterpenic acids in both bone marrow extract and plasma of CMG-treated rats by UHPLC-HRMS/MS analysis. In conclusion, CMG exhibited no genotoxic effects on bone marrow erythrocytes at the tested limit dose of 2000mg/kg body weight.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102155"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465868","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}

{"title":"Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways","authors":"Ruaa Adnan Mohammed ,&nbsp;Nada N. Al-Shawi","doi":"10.1016/j.toxrep.2025.102120","DOIUrl":"10.1016/j.toxrep.2025.102120","url":null,"abstract":"<div><div>5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent, but its hepatotoxic potential poses clinical challenges, as it induces oxidative stress, inflammation, and apoptosis in liver tissue. Butein, a natural chalcone flavonoid that possesses varied biological activity, such as anticancer, anti-inflammatory, and antiplatelet effects. This study aimed to evaluate the possible protective effects of Butein against 5-FU-induced hepatotoxicity in rats. Male albino rats were divided into 4 Groups (of 7 animals each): control, 5-FU, and two Butein-pretreated Groups (50 and 100 mg/kg/day, orally for 14 days) each before a single intraperitoneal dose of 150 mg/kg 5-FU, which was injected on day 14. Serum liver enzymes (ALT and AST), cytokines (IL-6, IL-10, and NF-κB), oxidative stress markers (MDA and GSH), TNF-α gene expression, and protein levels of caspase-3 and NRF2 were evaluated. Histological assessments were also conducted. 5-FU significantly elevated serum ALT and AST levels, increased NF-κB, IL-6, MDA, and TNF-α expression, and decreased IL-10, GSH, and NRF2 levels (p &lt; 0.05). Histological changes included sinusoidal dilation, congestion, and hepatocyte degeneration. Pre-treatment with Butein markedly attenuated these alterations, where both doses of Butein significantly reduced transaminases, pro-inflammatory cytokines, and oxidative stress markers while enhancing antioxidant defenses and anti-inflammatory IL-10 levels. Notably, the high dose of Butein restored NRF2 expression and reduced caspase-3 protein levels more effectively than the lower dose. Histologically, the high dose of Butein preserved normal hepatic architecture with minimal pathological changes. In conclusoin, Butein offers dose-dependent hepatoprotection against 5-FU-induced liver injury through the attenuation of oxidative stress, suppression of pro-inflammatory and apoptotic markers, and upregulation of antioxidant defenses; moreover, the histopathological evaluation further supported the biochemical and molecular findings, particularly at the 100 mg/kg/day, which preserved normal hepatic architecture and minimized cellular damage; and, thus support the prophylactic potentialof Butein in managing chemotherapeutic liver toxicity.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102120"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912098","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}