Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-11-17DOI: 10.1016/j.toxrep.2025.102166
Konstantine Chakhunashvili , Gela Gunashvili , Nino Jobava , George Chakhunashvili , Davit G. Chakhunashvili
{"title":"Collateral damage: Cardiovascular and respiratory implications of tear gas deployment during peaceful protest","authors":"Konstantine Chakhunashvili , Gela Gunashvili , Nino Jobava , George Chakhunashvili , 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 < 0.05).</div></div><div><h3>Results</h3><div>ECG abnormalities—including P-wave (p < 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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-10-28DOI: 10.1016/j.toxrep.2025.102153
Sarbani Hazra , Aditya Konar , Robb Welty , Uday B. Kompella
{"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 , Aditya Konar , Robb Welty , 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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-08-26DOI: 10.1016/j.toxrep.2025.102120
Ruaa Adnan Mohammed , Nada N. Al-Shawi
{"title":"Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways","authors":"Ruaa Adnan Mohammed , 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 < 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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-08-11DOI: 10.1016/j.toxrep.2025.102111
Wonkyun Jung , Mi-Jin Yang , Min-Sung Kang , Jin-Bae Kim , Kyung-Sik Yoon , Taekyung Yu , Cheolho Yoon , Hae Won Yang , Seong-Jin Choi , Eun-Jung Park
{"title":"Chronic lung tissue deposition of inhaled polyethylene microplastics may lead to fibrotic lesions","authors":"Wonkyun Jung , Mi-Jin Yang , Min-Sung Kang , Jin-Bae Kim , Kyung-Sik Yoon , Taekyung Yu , Cheolho Yoon , Hae Won Yang , Seong-Jin Choi , Eun-Jung Park","doi":"10.1016/j.toxrep.2025.102111","DOIUrl":"10.1016/j.toxrep.2025.102111","url":null,"abstract":"<div><div>Given the expected increase in exposure to airborne microplastics, we here aimed to assess the acute and subchronic toxicity of inhaled polyethylene microplastics (PE-MPs). At 24 h post-exposure (0, 125, 250, and 500 μg/lung), PE-MPs were found within alveolar macrophages in the lungs of PE-MP-treated mice, along with an increase in the total number of pulmonary cells and higher pulmonary levels of LDH, CXCL-1, and CCL-2. Similarly, when exposed twice for 14 days (weekly, 0, 125, 250, and 500 μg/lung), the total number of pulmonary cells and the levels of pulmonary chemokines and blood IgE were elevated, whereas the expression of surface proteins related to cell-to-cell interactions was inhibited on the pulmonary cells of mice exposed to PE-MPs. After 90 days of repeated intratracheal instillation (0, 5, 25, and 50 μg/lung), PE-MPs deposited in the lung tissues and increased dose-dependently both the total number of pulmonary cells and inflammatory cytokine levels. Furthermore, infiltration of inflammatory cells, formation of multinucleated giant cells, and thickening of the alveolar wall were noted in the lung tissues of PE-MP-treated male and female mice. While the production of IgA and IgG was inhibited in male and female mice following exposure to PE-MPs, the levels of IgE and IgM tended to increase. In addition, the expression of fibrillar collagens was enhanced in the lung tissues of PE-MP-treated mice. Taken together, we suggest that chronic pulmonary exposure to PE-MPs may cause immune dysregulation by impairing the antigen-presenting function of alveolar macrophages and that PE-MP-induced chronic inflammation may be linked to fibrotic lesions. In addition, we believe that these hypotheses will be clarified by further study of the effects of chronic exposure to PE-MPs on lung function.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102111"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852946","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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-09-17DOI: 10.1016/j.toxrep.2025.102129
Eunjin Sohn, Yu Jin Kim, Woo-Young Jeon, Sae-Rom Yoo, Kyuhyung Jo, Ami Lee, Aejin Kim, Jin Ah Ryuk, Chan-Sik Kim, Bu-Yeo Kim, Mee-Young Lee, Hye-Sun Lim, Youn-Hwan Hwang, Soo-Jin Jeong
{"title":"Subchronic oral toxicity and in vitro anti-neuroinflammatory evaluation of Ficus erecta leaves extract for potential functional food applications","authors":"Eunjin Sohn, Yu Jin Kim, Woo-Young Jeon, Sae-Rom Yoo, Kyuhyung Jo, Ami Lee, Aejin Kim, Jin Ah Ryuk, Chan-Sik Kim, Bu-Yeo Kim, Mee-Young Lee, Hye-Sun Lim, Youn-Hwan Hwang, Soo-Jin Jeong","doi":"10.1016/j.toxrep.2025.102129","DOIUrl":"10.1016/j.toxrep.2025.102129","url":null,"abstract":"<div><div><em>Ficus erecta</em> leaves, a traditional medicinal plant that is widely used in East Asia, have demonstrated promising cognitive-enhancing effects. However, the safety of its long-term administration has not been elucidated. Therefore, we evaluated the subchronic toxicity of an ethanol extract of <em>F. erecta</em> leaves (EEFE) by conducting 13-week repeated oral toxicity study using Sprague–Dawley (SD) rats. Male and female rats were administered EEFE at doses of 0, 500, 1000, or 2000 mg/kg/day. Clinical signs, body weight, food consumption, hematology, serum biochemistry, organ weights, and gross necropsy findings were also monitored. No treatment-related mortality or toxic effects were observed at any doses of EEFE. Accordingly, the No Observed Adverse Effect Level (NOAEL) was determined to be 2000 mg/kg/day for both sexes. Additionally, we observed anti-neuroinflammatory effects of EEFE and its active compound rutin in BV-2 microglia. EEFE and rutin significantly inhibited nitrate and prostaglandin E2 (PGE<sub>2</sub>) production in BV-2 cells. These results support the safety and anti-inflammatory action of EEFE for further development as a candidate herbal therapeutic or functional food for improving cognitive health and age-related conditions.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102129"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117666","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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-10-28DOI: 10.1016/j.toxrep.2025.102152
Kaustuv Basu , James Li, Luc Mongeau
{"title":"Unvaporized e-liquid toxicity elevates CD44-dependent hyaluronan catabolic gene expression and triggers inflammation in human vocal fold fibroblasts","authors":"Kaustuv Basu , James Li, Luc Mongeau","doi":"10.1016/j.toxrep.2025.102152","DOIUrl":"10.1016/j.toxrep.2025.102152","url":null,"abstract":"<div><div>Electronic (e)-cigarette and e-liquid exposure have been linked to vocal fold inflammation and dysphonia, yet no targeted non-surgical therapies currently exist. Hyaluronan, a key extracellular matrix component essential for vocal fold structure, repair, and function, is known to be dysregulated in inflammatory conditions; however, its metabolic gene response to e-liquid exposure in human vocal fold fibroblasts (hVFFs) remains uncharacterized. Hence, it is critical to understand hyaluronan metabolic gene expression under e-liquid toxicity to develop novel drug discovery strategies for vocal fold inflammation. To avoid confounding effects from thermal degradation and aerosol variability in conventional vapor models, hVFFs were exposed to nicotine-containing unvaporized e-liquid (0.125–1 mg/mL) for 24 h, revealing concentration-dependent changes in cell morphology and viability (p < 0.05). The lethal concentration 50 (LC₅₀) was determined to be 0.437 mg/mL and used for short-term (24 h) and extended (72–96 h) exposures. Extended exposure induced intracellular reactive oxygen species (ROS), inflammation, suppressed collagenolysis, and increased the collagen 1 A: collagen 3 A ratio, suggesting fibrotic remodeling. Short-term exposure downregulated hyaluronan synthases (HAS1, HAS2, HAS3) and catabolic genes (HYAL2, CD44), reducing extracellular hyaluronan levels. In contrast, extended exposure repressed HAS1 and HAS2 while upregulating HAS3, CD44, and HYAL2, indicating enhanced hyaluronan degradation and accumulation of proinflammatory low molecular weight hyaluronan. CD44 silencing reduced <em>IL-8</em> mRNA expression, confirming its role in hVFF inflammation. These findings provide the first mechanistic insight into unvaporized e-liquid-induced dysregulation of hyaluronan metabolism in hVFFs, offering a foundation for biomarker identification and therapeutic development targeting e-cigarette-associated vocal fold inflammation.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102152"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415836","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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-11-05DOI: 10.1016/j.toxrep.2025.102156
John Oludele Olanlokun , Oluseye Osovehe Yahaya , Cecilia Opeyemi Babarinde , Oluwakemi Marvellous Oloke , Paul Steenkamp , Gerhard Prinsloo
{"title":"Comparative effects of antimalarial drugs on oxidative phosphorylation, mitochondrial dynamics and mitophagy in Plasmodium berghei-infected mice","authors":"John Oludele Olanlokun , Oluseye Osovehe Yahaya , Cecilia Opeyemi Babarinde , Oluwakemi Marvellous Oloke , Paul Steenkamp , Gerhard Prinsloo","doi":"10.1016/j.toxrep.2025.102156","DOIUrl":"10.1016/j.toxrep.2025.102156","url":null,"abstract":"<div><div>Mitochondria occupy prominent position in cell metabolism. Information on changes in host mitochondrial capacity in electron transport system, dynamics and mitophagy in mice infected with resistant <em>Plasmodium berghei</em> and thereafter treated with some orthodox drugs, is critical to the survival and the organelles’ metabolism. In this study, the effects of some antimalarial drugs were investigated on mitochondrial permeability transition (mPT) pore opening, F<sub>o</sub>F<sub>1</sub> ATPase and lipid peroxidation, oxidative phosphorylation and mitochondrial dynamics in mice infected with chloroquine resistant (ANKA) strain of <em>Plasmodium berghei</em>. Thirty-five Swiss-mice (18 ± 3 g) were infected intraperitoneally with chloroquine resistant (ANKA) strain of <em>Plasmodium berghei</em> and treated orally and once daily with (10 mg/kg) dose of Amodiaquine artesunate (AA), Artemether-Lemefantrine (AL), Sulfadoxine- pyrimethamine (SP) and Artesunate (ART), On day 6, animals were sacrificed and livers were removed. Liver mitochondria were isolated and mitochondrial permeability transition (mPT) pore opening, F<sub>0</sub>F<sub>1</sub> ATPase (mATPase) and lipid peroxidation (mLPO) were determined spectrophotometrically. Gene expressions on liver mitochondrial complexes I, II, III, IV and V, DNM1L, DRP1, OPA 1 Mitofusin 1 and 2, PINK 1, FUNDC1, PGC-1α and prohibitins 1 and 2 were determined using gel electrophoresis. AA, AL and SP did not significantly open the mPT pore while ART caused its opening (7 fold) and enhance mitochondrial F<sub>o</sub>F<sub>1</sub> ATPase (<em>P</em> < 0.01), SP and AA induced peroxidation of mitochondrial membrane phospholipids (<em>P</em> < 0.01) when compared to the infected control. SP and AA significantly silenced the expressions of mitochondrial complexes. The effects of these drugs on mitochondrial fission and fusion vary significantly: AA down-regulated the expressions of <em>DRP1, OPA 1</em> while AA, AL and ART decreased the expression of <em>Mitofusin 2</em> as observed in the infected control. Significant down-regulation in the expressions of <em>PINK 1</em> by SP, <em>FUNDC1</em> by AA and AL, <em>DNM1L</em> by ART, <em>PGC-1α</em> by AA, AL, and ART, and <em>prohibitins 1</em> and <em>2</em> by AA and AL similar to the infected control were observed. This study showed that host mitochondria respond differently to antimalarial drugs.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102156"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525299","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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-11-21DOI: 10.1016/j.toxrep.2025.102171
Yehao Sun , Gagandeep Kaur , Felix Effah , Alan Friedman , Irfan Rahman
{"title":"Cytotoxic and oxidative effects of commercially available propylene glycol (PG) and vegetable glycerin (VG): Common humectants in electronic cigarettes","authors":"Yehao Sun , Gagandeep Kaur , Felix Effah , Alan Friedman , Irfan Rahman","doi":"10.1016/j.toxrep.2025.102171","DOIUrl":"10.1016/j.toxrep.2025.102171","url":null,"abstract":"<div><div>The effects of commercially available brands of common e-liquid humectants – propylene glycol (PG) and vegetable glycerin (VG) are not known. This study evaluates the toxicities of commercially available PG and VG mixtures compared to their analytically pure grade chemicals. The pH and the viscosity of 50:50 PG/VG mixtures from four different commercially available brands and a pure chemical mixture were measured. Commercially available brands of PG/VG generally had higher pH (up to ∼6.25) and viscosity values (up to 16.4 %) than the pure chemical mixture (pH = 5.5; viscosity = 12.9 %). GC-MS spectra provide evidence of impurities in commercially available PG, but not VG liquids when compared to pure chemicals. While we observe variation in the level of acellular reactive oxygen species generated by commercial mixtures as compared to the pure chemical, the protein carbonylation levels were comparable for both the mixtures, thus indicating variation in the nature of the oxygen species generated upon aerosolization. No noticeable change was observed upon studying the human monocytic U937 cellular responses upon treatment with sub-toxic concentrations of PG/VG mixtures; however, a decrease in the basal IL-8 production was observed at higher concentrations (1 %) of PG/VG treatment. The commercially available PG/VG mixtures show comparable oxidative and biological effects to the pure chemical. However, GC-MS data identified impurities which may explain our observation of a variable ROS profile in each PG/VG mixture. Future work on the brand-specific toxicity of PG/VG or its usage is warranted to inform regulatory guidelines for e-cigarettes.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102171"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620700","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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-11-24DOI: 10.1016/j.toxrep.2025.102174
Haneen Amawi , Rawan Alhazaimeh , Alaa M. Hammad , Aseel O. Rataan , Sahar Alsheyab , Tayma Maklouf , Bahaa Al-Trad , Karem H. Alzoubi
{"title":"Modulating morphine-induced conditioned place preference: The role of diclofenac sodium","authors":"Haneen Amawi , Rawan Alhazaimeh , Alaa M. Hammad , Aseel O. Rataan , Sahar Alsheyab , Tayma Maklouf , Bahaa Al-Trad , Karem H. Alzoubi","doi":"10.1016/j.toxrep.2025.102174","DOIUrl":"10.1016/j.toxrep.2025.102174","url":null,"abstract":"<div><div>Morphine is known to induce strong reward-related behaviors, contributing to its high addiction potential. Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac sodium, have been suggested to modulate neuroinflammatory pathways involved in addiction. This study aimed to evaluate the effect of diclofenac sodium on morphine-induced conditioned place preference (CPP) in rats and investigate its underlying anti-inflammatory and antioxidant mechanisms. Female rats were subjected to a morphine-induced conditioned place preference (CPP) protocol. Diclofenac sodium (25 mg/kg) was administered 30 min prior to morphine conditioning sessions via injection. Post-conditioning, brain tissue samples were analyzed to measure the mRNA expression levels of cyclooxygenase enzymes (<em>Cox1</em>, <em>Cox2</em>), nuclear factor kappa B (<em>Nf-κB</em>), interleukin-6 (<em>Il-6</em>), and interleukin-1β (<em>Il-1β</em>). Oxidative stress in serum samples was assessed through catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) enzyme activity. Morphine significantly induced CPP, indicating a strong reward effect. Diclofenac sodium administration markedly attenuated this morphine-induced seeking behavior. This behavioral effect was accompanied by a significant reduction in the expression levels of <em>cox1</em>, <em>cox2</em>, <em>nf-κB</em>, and <em>il-6, and a significant increase in il-1β mRNA levels compared to the</em> morphine group. Additionally, diclofenac sodium significantly reduced oxidative stress, as indicated by decreased SOD activity when combined with morphine compared to the morphine group. In conclusion, Diclofenac sodium effectively attenuates morphine-induced reward behavior in the CPP model, potentially through modulation of inflammatory and oxidative stress pathways. These findings support the therapeutic potential of diclofenac sodium in managing opioid-seeking behaviors and provide insights into its anti-inflammatory and antioxidant mechanisms of action.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102174"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620715","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}
Toxicology ReportsPub Date : 2025-12-01Epub Date: 2025-10-23DOI: 10.1016/j.toxrep.2025.102146
Olorunfemi R. Molehin , Oluwasegun S. Dauda , Oluwakemi V. Adeleke , Joy F. David , Testimony O. Oso , Anne A. Adeyanju
{"title":"Comparative analysis of antioxidant and antimicrobial potentials of different extracts of Turraea vogelii leaves","authors":"Olorunfemi R. Molehin , Oluwasegun S. Dauda , Oluwakemi V. Adeleke , Joy F. David , Testimony O. Oso , Anne A. Adeyanju","doi":"10.1016/j.toxrep.2025.102146","DOIUrl":"10.1016/j.toxrep.2025.102146","url":null,"abstract":"<div><div><em>Turraea vogelii Hook</em>.f. is a plant valued for its medicinal properties. The aim of this study is to investigate the comparative analysis of antioxidant and antimicrobial potentials of different extracts of <em>Turrea vogelii Hook</em>.f. leaves. The fresh leaves of the plant were harvested, air-dried, ground, and extracted with three solvents based on polarity (Dichloromethane (DCM), Ethyl Acetate, and n-hexane) via a maceration procedure. The antioxidant and antibacterial potential of these compounds was tested to assess their efficacy. Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography Mass Spectrometry (GC-MS) were used to analyse the functional groups and organic compounds present in the drug materials, respectively. Antioxidant screening identified flavonoids (24.63 ± 0.47, 19.96 ± 0.17, 21.04 ± 0.04), phenols (20.18 ± 0.4, 17.61 ± 0.11, 8.65 ± 0.15) in 100μg/mL of the DCM, ethyl acetate, and n-hexane crude extracts, respectively. The antibacterial evaluation showed that the DCM extract demonstrated potent activity, with minimum inhibitory concentration (MIC) values as low as 3.125 µg/mL and minimum bactericidal concentration (MBC) values ranging from 6.25 µg/mL to 50 µg/mL against pathogens such as <em>Escherichia coli</em> ATCC 35218, Staphylococcus aureus ATCC 2921, <em>Escherichia coli</em> ATCC 25922, <em>Pseudomonas aeruginosa</em> ATCC 27853, <em>Klebsiella pneumoniae</em> ATCC 700303, and <em>Salmonella typhi</em> ATCC14028. FTIR analysis identified several functional groups in the extract, including hydroxyls, alkanes, amides, ethers, and amines, indicative of diverse bioactive compounds, and GC-MS identified key compounds like squalene and Hexanoic acid. The results highlight the potential of plant leaves to possess notable antioxidants and antibacterial properties, supporting their traditional use in folk medicine and paving the way for the development of novel antibacterial agents.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102146"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361679","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}