Drug and Chemical Toxicology最新文献_第4页

In silico molecular docking and in vitro analysis of atomoxetine.

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-27 DOI: 10.1080/01480545.2025.2452859

Nurullah Bolat, Merve Meliha Hız-Çelikliyurt, Erhan Akıncı, Gülsüm Akkuş, Melih Günay, Şükrü Alperen Korkmaz

{"title":"In silico molecular docking and in vitro analysis of atomoxetine.","authors":"Nurullah Bolat, Merve Meliha Hız-Çelikliyurt, Erhan Akıncı, Gülsüm Akkuş, Melih Günay, Şükrü Alperen Korkmaz","doi":"10.1080/01480545.2025.2452859","DOIUrl":"10.1080/01480545.2025.2452859","url":null,"abstract":"Although atomoxetine, a selective norepinephrine reuptake inhibitor, is widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD), there is limited data on its cytogenetic effects. This study aimed to investigate the cytotoxicity and genotoxicity of atomoxetine in vitro and silico. Chromosome aberration and micronucleus assays were used to analyze the genotoxic effect of atomoxetine in human peripheral blood lymphocytes under culture conditions. The mitotic index was assessed for cytotoxic potential. For the docking analysis, DNA receptor (1BNA) was prepared with ChimeraX, and the Atomoxetine molecule was optimized by Avogadro2.0 software. In silico molecular docking analysis was carried out utilizing SwissDock online platform. The results obtained were visualized using ChimeraX and Pymol software. Atomoxetine doses of 9.6 µg/mL (equal to about 1.2 mg/kg as a maintenance dose), 14.4 µg/mL (equal about to 1.8 mg/kg as the highest dose systematically tested), 48.0 µg/mL (equal about to 6 mg/kg as five times the maintenance dose) and 96.0 µg/mL (equal about to 12 mg/kg as ten times the maintenance dose) were analyzed. The findings clearly indicate that atomoxetine has no genotoxic effect at the therapeutic dose. However, we observed genotoxic effects at 48.0 and 96.0 µg/mL doses. No strong binding affinity occurs in silico analyses. As one of the initial inquiries into the in silico and in vitro appraisal of atomoxetine's genotoxic impacts, the research has established that atomoxetine does not significantly affect the frequency of chromosomal damage or micronucleus formation. Genotoxic effects should be kept in mind at doses above clinical practice.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel chlorinated oxime K870 protects rats against paraoxon poisoning better than obidoxime.

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-27 DOI: 10.1080/01480545.2025.2454279

Žana M Maksimović, Sonja T Marinković, Đorđe Đukanović, Nebojša Mandić-Kovačević, Snežana Uletilović, Mladen Duran, Kamil Kuča, Kamil Musilek, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković

{"title":"Novel chlorinated oxime K870 protects rats against paraoxon poisoning better than obidoxime.","authors":"Žana M Maksimović, Sonja T Marinković, Đorđe Đukanović, Nebojša Mandić-Kovačević, Snežana Uletilović, Mladen Duran, Kamil Kuča, Kamil Musilek, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković","doi":"10.1080/01480545.2025.2454279","DOIUrl":"https://doi.org/10.1080/01480545.2025.2454279","url":null,"abstract":"The aim of this study was to determine the antidotal potential of the chlorinated oxime K870 compared to obidoxime, as a monotherapy and in combination with atropine, in paraoxon (POX)-poisoned rats. The treatment doses of oximes were chosen as 20% of their LD50 values. The protective ratio (PR) of oxime K870 with atropine was significantly higher than that of obidoxime with atropine (68.8 and 125.0, respectively). In the biochemical part of the experiment POX subcutaneously (s.c.) (0.75% LD50) was administered and followed by oxime K870 or obidoxime i.m. 1 min later. Acetylcholinesterase (AChE) activity was determined spectrophotometrically in cerebrum, cerebellum, brainstem, diaphragm, and erythrocytes. Carboxylesterase activity was determined in plasma and liver. Both oximes successfully reactivated AChE in brain (cerebrum, cerebellum, and brainstem), diaphragm and erythrocytes, but the oxime K870 performed better than obidoxime. Both oximes reactivated carboxylesterase, obidoxime better in plasma and oxime K870 better in liver. In conclusion, the oxime K870, when co-administered with atropine, is a more effective antidote than the obidoxime-atropine combination in POX-poisoned rats.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective effects of herbal compounds against cyclophosphamide-induced organ toxicity: a pathway-centered approach.

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-23 DOI: 10.1080/01480545.2025.2455442

Prathap Srirangan, Evan Prince Sabina

{"title":"Protective effects of herbal compounds against cyclophosphamide-induced organ toxicity: a pathway-centered approach.","authors":"Prathap Srirangan, Evan Prince Sabina","doi":"10.1080/01480545.2025.2455442","DOIUrl":"https://doi.org/10.1080/01480545.2025.2455442","url":null,"abstract":"Cyclophosphamide is a key component of numerous chemotherapeutic protocols, demonstrating broad-spectrum efficacy against various malignancies and non-cancerous conditions. This review examines CPM's metabolic pathways, therapeutic applications, and its resulting organ-specific toxicities. Despite its clinical benefits in treating nephrotic syndrome, encephalomyelitis, breast cancer, ovarian cancer, and other diseases, CPM is associated with significant adverse effects on the kidneys, liver, heart, lungs, and intestines. The discussion delves into the molecular mechanisms underlying these toxicities, highlighting dysregulation in key signaling pathways, including Nrf2, NF-κB, MAPK/ERK, and AKT. In addressing these challenges, recent studies have identified various herbal drugs and phytochemicals capable of mitigating CPM-induced toxicity. Notable compounds such as cinnamaldehyde, baicalin, quercetin, and curcumin have demonstrated protective effects. Integrating these herbal formulations with CPM therapy is proposed to enhance patient safety and treatment efficacy. This review underscores the influence of CPM on apoptosis and inflammation pathways, which lead to alterations in organ-specific biomarkers. Phytochemicals may exert protective effects by restoring disrupted signaling pathways and normalizing altered biomarkers. The compilation of phytochemicals presented in this review serves as a valuable resource for researchers exploring other herbal products with potential protective effects against CPM toxicity. A significant gap in the current literature is the lack of clinical trials evaluating phytochemicals that mitigate CPM toxicity in vivo. Rigorous clinical studies are necessary to establish the efficacy and safety of herbal formulations in cancer treatment. Such research will clarify the role of natural remedies in complementing conventional therapies, ultimately improving patient outcomes.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-43"},"PeriodicalIF":2.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NO-mediated DNA damage induced by polystyrene nanoparticles triggers program cell death in mesenchymal stem cells. 聚苯乙烯纳米颗粒诱导no介导的DNA损伤触发间充质干细胞程序性细胞死亡。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-21 DOI: 10.1080/01480545.2025.2453580

Vesna Matovic, Biljana Ljujic, Marina Miletic Kovacevic, Olivera Milosevic-Djordjevic, Nevena Milivojevic, Sandra Nikolic, Marina Gazdic Jankovic

{"title":"NO-mediated DNA damage induced by polystyrene nanoparticles triggers program cell death in mesenchymal stem cells.","authors":"Vesna Matovic, Biljana Ljujic, Marina Miletic Kovacevic, Olivera Milosevic-Djordjevic, Nevena Milivojevic, Sandra Nikolic, Marina Gazdic Jankovic","doi":"10.1080/01480545.2025.2453580","DOIUrl":"https://doi.org/10.1080/01480545.2025.2453580","url":null,"abstract":"Daily contact with considerable amounts of polystyrene nanoparticles (PSNPs) may cause harmful effects on the living organisms, through mechanisms that are not fully understood. The study aimed to evaluate the cytotoxic and genotoxic effects of PSNPs (size 200 nm and 40 nm) in mesenchymal stem cells (MSCs). In order to estimate cellular uptake and retention of nanoplastics, PSNP-treated cells have been analyzed by transmission electron microscopy. For assessing morphology and viability of MSCs after PSNP treatment at two environmentally relevant doses (0.47 and 4.7 μl/ml) for 24 hours, HE and Giemsa staining were performed. Annexin V‑FITC/PI assay was used to quantify PSNPs-mediated cell death. Genotoxicity of PSNPs was evaluated by Comet test. The capacity of PSNPs to trigger the production of free radicals in MSCs was also evaluated. TEM confirmed endocytosis of PSNPs. Decreased cell volume, nuclear hyperchromatism, edge aggregation, and formation of densely stained apoptotic bodies, indicated that PSNP-treated MSCs undergo apoptosis. The presented data showed that both concentration of PS particles significantly increased early apoptotic cell death in comparison to untreated cells. Moreover, both doses of PSNPs significantly increased the genetic damage index in MSCs in dose-dependent manner. In conclusion, PSNPs penetrate, accumulate and induce cytotoxic and genotoxic damage in MSCs.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of the effects of silymarin and vitamin C on kidney damage and aquaporin-2 downregulation in lithium-induced nephrogenic diabetes insipidus in rats. 研究水飞蓟素和维生素 C 对锂引起的肾性尿崩症大鼠肾脏损伤和水通道蛋白-2 下调的影响

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-14 DOI: 10.1080/01480545.2025.2450475

Seda Yakut, Berrin Tarakçı Gençer, Mehmet Hanifi Yalçın, Süleyman Aydın, Hayati Yüksel

{"title":"Investigation of the effects of silymarin and vitamin C on kidney damage and aquaporin-2 downregulation in lithium-induced nephrogenic diabetes insipidus in rats.","authors":"Seda Yakut, Berrin Tarakçı Gençer, Mehmet Hanifi Yalçın, Süleyman Aydın, Hayati Yüksel","doi":"10.1080/01480545.2025.2450475","DOIUrl":"https://doi.org/10.1080/01480545.2025.2450475","url":null,"abstract":"Although lithium (LIT) therapy is key in managing bipolar disorder long-term, prolonged use significantly contributes to acquired Nephrogenic Diabetes Insipidus (NDI). This study examined whether combining Silymarin (SIL) with Vitamin C (Vit C) enhances protection against lithium-induced nephrotoxicity in rats, comparing their individual antioxidant effects as well. Rats subjected to Li exposure were provided with a standard commercial diet supplemented with 80 mmol LiCl per kilogram for 28 days. Concurrently, SIL and Vit C were administered orally at dosages of 200 and 100 mg/kg body weight, respectively, throughout the 28 days. The study assessed levels of reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA), as well as the enzyme activity of superoxide dismutase (SOD), to evaluate the protective effects of SIL and Vit C against oxidative stress. Aquaporin-2 (AQP2) levels in kidney tissues were evaluated using immunohistochemistry and ELISA. Serum and urine parameters (sodium, potassium, creatinine, blood urea nitrogen [BUN], and urea) and serum lithium levels were also measured. Lithium-induced nephrotoxicity showed increased renal toxicity markers and decreased antioxidant enzyme activity. SIL administration significantly reduced markers of kidney tissue toxicity, increased antioxidant enzyme activities, regulated the aforementioned physiological parameters in blood and urine, and downregulated AQP2 expression in the kidney. However, Vit C administration did not demonstrate a significant protective effect against lithium-induced renal toxicity. These findings indicate that SIL effectively protects against lithium-induced nephrotoxicity, whereas Vitamin C does not exhibit this protective effect.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aflatoxin B₁ and fumonisin B₁ exposure and adverse birth outcomes in HIV-infected and HIV-uninfected women from Harare, Zimbabwe. 津巴布韦哈拉雷感染艾滋病毒和未感染艾滋病毒妇女的黄曲霉毒素B1和伏马菌素B1暴露和不良分娩结局

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-04 DOI: 10.1080/01480545.2024.2448675

Tatenda Clive Murashiki, Privilege Tendai Munjoma, Rutendo B L Zinyama-Gutsire, Isaac Mutingwende, Lovemore Ronald Mazengera, Kerina Duri

{"title":"Aflatoxin B1 and fumonisin B1 exposure and adverse birth outcomes in HIV-infected and HIV-uninfected women from Harare, Zimbabwe.","authors":"Tatenda Clive Murashiki, Privilege Tendai Munjoma, Rutendo B L Zinyama-Gutsire, Isaac Mutingwende, Lovemore Ronald Mazengera, Kerina Duri","doi":"10.1080/01480545.2024.2448675","DOIUrl":"https://doi.org/10.1080/01480545.2024.2448675","url":null,"abstract":"Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are toxic secondary products of fungi that frequently contaminate staple crops in resource-limited settings. Antenatal AFB1 and FB1 exposure may cause adverse birth outcomes. We conducted a retrospective substudy nested in a case-control cohort of HIV-infected and HIV-uninfected women ≥20 weeks gestation from Harare, Zimbabwe. Urinary aflatoxin M1 (AFM1) and FB1, biomarkers of AFB1 and FB1 exposure, respectively, were quantified in random antenatal urine via ELISA and grouped into tertiles. The adverse birth outcomes considered were low birth weight, preterm birth (PTB), small for gestational age, stillbirth, birth defects, neonatal death, neonatal jaundice and perinatal death (PD). We evaluated any associations between adverse birth outcomes and exposure to AFB1, FB1, or the AFB1-FB1 combination via a multivariable logistic regression controlled for potential confounders. We enrolled 94 HIV-infected and 81 HIV-uninfected women. In HIV-infected, AFM1 was detected in 46/94 (49%), and FB1 was detected in 86/94 (91%). In HIV-uninfected, AFM1 was detected in 48/81 (59%), and FB1 was detected in 74/81 (91%). Among all women, AFM1 tertile 3 was associated with PD (OR: 6.95; 95% CI: 1.21-39.78). In the same population, AFM1 tertiles 2 (OR: 13.46; 95% CI: 1.20-150.11) and 3 (OR: 7.92; 95% CI: 1.08-58.19) were associated with PTB. In HIV-infected, AFM1 tertile 2 was associated with PTB (OR: 64.73; 95% CI: 2.37-177.93). Our results revealed an association between AFB1 exposure and PD and PTB in women, including those infected with HIV. Public health and nutrition measures are necessary to mitigate mycotoxins.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial toxicity of selected natural compounds: in vitro assessment and in silico molecular docking and dynamics simulation. 精选天然化合物的线粒体毒性：体外评估及硅学分子对接和动力学模拟。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-10-16 DOI: 10.1080/01480545.2024.2412775

Ali Ergüç, Gökay Albayrak, Muhammed Tilahun Muhammed, Fuat Karakuş, Ege Arzuk

{"title":"Mitochondrial toxicity of selected natural compounds: in vitro assessment and in silico molecular docking and dynamics simulation.","authors":"Ali Ergüç, Gökay Albayrak, Muhammed Tilahun Muhammed, Fuat Karakuş, Ege Arzuk","doi":"10.1080/01480545.2024.2412775","DOIUrl":"10.1080/01480545.2024.2412775","url":null,"abstract":"Prangos uechtritzii Boiss & Hausskn stands out for its rich bioactive constituents including prantschimgin (PRA), imperatorin (IMP), suberosin (SUB), adicardin (ADI), and oxypeucedanin hydrate (OPH) in the Apiaceae family. Although these molecules contribute to several biological activities, their mitochondrial toxicity were not illuminated in depth with the appropriate in vitro and in silico models. Cell viability studies investigated the cytotoxic activities of molecules in HepG2 cells by replacing glucose with galactose due to Warburg effects. Mitochondrial toxicity (mitotoxicity) parameters such as cellular adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) levels were assessed with cytotoxic concentrations of selected molecules. Molecular docking and dynamics studies were also conducted against mitochondrial electron transport chain (ETC) complexes (I-V) with selected compounds. In vitro results showed that PRA, SUB, and IMP reduced cell viability more in galactose media compared to high glucose media in a dose-dependent manner. PRA, IMP, and SUB decreased ATP levels and MMP, especially in the galactose medium. The in silico study revealed that PRA, IMP, and SUB might bind to complexes I-V at different levels. The docking study demonstrated that PRA had the highest binding potential with the complexes, higher than the standard ligands in some cases. The molecular dynamics (MD) simulation study showed that PRA formed stable complexes with complexes II, III, and IV. In addition, PRA was anticipated to remain inside the binding site of complex II most stably during the 230 ns simulation period. Our study suggests that PRA, IMP, and SUB exhibit mitotoxicity.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"199-209"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cannabidiol mitigates methotrexate-induced hepatic injury via SIRT-1/p53 signaling and mitochondrial pathways: reduces oxidative stress and inflammation. 大麻二酚通过SIRT-1/p53信号传导和线粒体途径减轻甲氨蝶呤诱导的肝损伤：减少氧化应激和炎症。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1080/01480545.2024.2425994

Ilter Ilhan, Halil Asci, Ibrahim Aydın Candan, Mehtap Savran, Orhan Berk Imeci, Mehmet Abdulkadir Sevuk

{"title":"Cannabidiol mitigates methotrexate-induced hepatic injury via SIRT-1/p53 signaling and mitochondrial pathways: reduces oxidative stress and inflammation.","authors":"Ilter Ilhan, Halil Asci, Ibrahim Aydın Candan, Mehtap Savran, Orhan Berk Imeci, Mehmet Abdulkadir Sevuk","doi":"10.1080/01480545.2024.2425994","DOIUrl":"10.1080/01480545.2024.2425994","url":null,"abstract":"Methotrexate (MTX), a widely used chemotherapeutic agent, often induces hepatotoxicity, limiting its clinical utility. Cannabidiol (CBD), derived from hemp, possesses antioxidant, anti-inflammatory, and antiapoptotic properties. This study aims to investigate CBD's protective effects against MTX-induced liver injury and elucidate the underlying mechanisms. Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (20 mg/kg intraperitoneally [i.p.] once), MTX+CBD (20 mg/kg i.p. once + 5 mg/kg i.p. for seven days), and CBD (5 mg/kg, i.p. for seven days). Biochemical analyses of serum and liver tissues were performed to assess oxidative stress markers (total oxidant status, total antioxidant status, oxidative stress index), liver function tests (AST, ALT), and antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase). Histopathological and immunohistochemical examinations were conducted to evaluate liver tissue damage and TNF-α expression. Genetic analyses were performed to measure the expression levels of SIRT-1, p53, Bcl-2, and Bax genes using RT-qPCR. MTX administration increased oxidative stress markers, liver enzymes, TNF-α, p53, and Bax levels while decreasing antioxidant defenses and SIRT-1 expression. CBD administration reversed these alterations effectively. CBD mitigated MTX-induced hepatotoxicity by reducing oxidative stress, inflammation, and apoptosis. It activates antioxidant defenses via SIRT-1 upregulation, suppresses inflammation by reducing TNF-α, and prevents apoptosis by modulating p53, Bcl-2, and Bax gene expressions. These findings suggest CBD could be a promising therapeutic agent for chemotherapy-induced liver damage. Further research is warranted to explore additional pathways and broader molecular mechanisms.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"210-218"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The neuroprotective effect of 1,25-dyhydroxyvitamin D₃ (calcitriol) and probiotics on the rotenone-induced neurotoxicity model in SH-SY5Y cells. 1,25-二羟维生素 D3（钙三醇）和益生菌对鱼藤酮诱导的 SH-SY5Y 细胞神经毒性模型的神经保护作用。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1080/01480545.2024.2429621

Fatma Hazan Gul, Nuh Mehmet Bozkurt, Nalan Hakime Nogay, Gokhan Unal

{"title":"The neuroprotective effect of 1,25-dyhydroxyvitamin D3 (calcitriol) and probiotics on the rotenone-induced neurotoxicity model in SH-SY5Y cells.","authors":"Fatma Hazan Gul, Nuh Mehmet Bozkurt, Nalan Hakime Nogay, Gokhan Unal","doi":"10.1080/01480545.2024.2429621","DOIUrl":"10.1080/01480545.2024.2429621","url":null,"abstract":"This study aimed to investigate the neuroprotective role of probiotics and 1,25-dyhydroxyvitamin D3 (calcitriol) against neurotoxicity on rotenone-induced human neuroblastoma cell line SH-SY5Y. Rotenone was administered to induce neurotoxic effects in SH-SY5Y cells. Calcitriol and probiotics were administered at different concentrations as pre- and post-treatment. The thiazolyl blue tetrazolium bromide (MTT) assay was performed to measure cell viability. Intracellular protein levels of antioxidant enzymes (protein tyrosine kinase (PTK), superoxide dismutase (SOD), glutathione peroxidase (GSH), glutathione reductase (GSR), and catalase (CAT)) were determined by the enzyme-linked immunosorbent assay (ELISA). Rotenone (150 nM) reduced (p < 0.001) cell viability compared to control cells. Single and combined pretreatments with probiotics (0.01 mg/ml, 0.05 mg/ml, and 0.1 mg/ml) and calcitriol (1.25 µM, 2.5 µM, and 5 µM) increased (p < 0.05) cell viability compared to rotenone group. In the pre- and post-treatment design, all treatment groups increased the SOD and GSH levels and decreased the GSR levels compared to rotenone. None of the pretreatments reversed the PTK levels (except probiotics: 0.01 mg/ml). Calcitriol (2.5 µM) increased the CAT levels in pretreatment design, and probiotics (0.05 mg/ml and 0.1 mg/ml) increased CAT levels in post-treatment design compared to rotenone group. Calcitriol and probiotics protect against rotenone-induced neurotoxicity in SH-SY5Y cells by decreasing reactive oxygen species (ROS) and increasing antioxidant enzyme parameters. These neuroprotective effects of calcitriol and probiotics against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for their potential clinical use in the treatment of Parkinson's disease (PD).","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"72-83"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced antibacterial and genoprotective properties of nanoliposomal Satureja hortensis L. essential oil. 增强纳米脂质体 Satureja hortensis L. 精油的抗菌和基因保护特性。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-06-04 DOI: 10.1080/01480545.2024.2362180

Munevver Muge Cagal, Gokce Taner, Sadık Kalaycı, Gulengul Duman

{"title":"Enhanced antibacterial and genoprotective properties of nanoliposomal Satureja hortensis L. essential oil.","authors":"Munevver Muge Cagal, Gokce Taner, Sadık Kalaycı, Gulengul Duman","doi":"10.1080/01480545.2024.2362180","DOIUrl":"10.1080/01480545.2024.2362180","url":null,"abstract":"Nanoliposomes are drug delivery systems that improve bioavailability by encapsulating therapeutic agents. The main objective of this study was to investigate the effects of nanoliposomal (NL) formulation on enhancing the bioavailability of essential oil. The essential oil of Satureja hortensis (SHO) was encapsulated in nanoliposomes (SHNLs). Physicochemical characterizations of NL formulations (size, charge, polydispersity index [PDI]) were evaluated by dynamic light scattering technique. The nanoliposome encapsulation efficiency (EE) was calculated as 89.90%. The prepared bionanosystems demonstrated significant antibacterial activities against Escherichia coli ATCC 10536, Pseudomonas aeruginosa ATCC 15442, and Staphylococcus aureus ATCC as determined by the agar diffusion method and microdilution tests. Minimum inhibitory concentration (MIC) values for SHNLs were found to be 5.187 µg/µL for E. coli and 2.59 µg/µL for both P. aeruginosa and S. aureus. Importantly, despite the lower substance content, both SHNLs and SHO exhibited comparable antibacterial activity against all tested strains. Furthermore, in order to determine the toxicity profile and possible effects on DNA damage or repair both the genotoxic and antigenotoxic effects of SHNLs were assessed using the cytokinesis-blocked micronucleus (CBMN) method in human lymphocyte cultures. The experimental data collectively indicate that the NL formulation of the S. hortensis essential oil enhances antibacterial activities and provides genoprotective effects against DNA damage. This highlights the significance of liposomal formulations of antioxidants in augmenting their biological activity. The results indicate that SHNLs can be a safe antibacterial agent for the pharmaceutical industry.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"180-186"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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