Drug and Chemical Toxicology最新文献_第9页

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}

引用次数: 0

Hepatoprotective potentials of Usnea longissima Ach. and Xanthoparmelia somloensis (Gyelnik) Hale extracts in ethanol-induced liver injury. Usnea longissima Ach.和 Xanthoparmelia somloensis (Gyelnik) Hale 提取物在乙醇诱导的肝损伤中的保肝潜力。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-09-25 DOI: 10.1080/01480545.2024.2407867

Mehmet Berköz, Ali Aslan, Oruç Yunusoğlu, Mirosław Krośniak, Renata Francik

{"title":"Hepatoprotective potentials of Usnea longissima Ach. and Xanthoparmelia somloensis (Gyelnik) Hale extracts in ethanol-induced liver injury.","authors":"Mehmet Berköz, Ali Aslan, Oruç Yunusoğlu, Mirosław Krośniak, Renata Francik","doi":"10.1080/01480545.2024.2407867","DOIUrl":"10.1080/01480545.2024.2407867","url":null,"abstract":"In our study, the antioxidant and anti-inflammatory effects of different lichen applications were investigated in rats using an experimental ethanol toxicity model. 48 rats were used in the study and they were divided into 6 groups with 8 rats in each group. These groups were: control, ethanol (2 g/kg), ethanol + Usnea longissima Ach. (200 mg/kg), ethanol + Usnea longissima Ach. (400 mg/kg), ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (100 mg/kg) and ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (200 mg/kg). The experimental work continued for 21 days. Lichen extracts and ethanol were administered by gavage to rats divided into groups. According to the experimental protocol, the experimental animals were sacrificed and their liver tissues were isolated. Biochemical parameters in serum, histological examinations, oxidative stress and inflammation parameters both at biochemical and molecular level in liver tissues were performed. Oxidative stress and inflammatory response were increased in the liver tissue of rats treated with ethanol for 21 days, and liver functions were impaired. It was found that U. longissima and X. somloensis extracts showed good antioxidant activity and conferred protective effects against ethanol-induced oxidative stress and inflammation. This could be attributed to the presence of secondary metabolites in the extract, which act as natural antioxidants and could be responsible for increasing the defence mechanisms against free radical production induced by ethanol administration.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"136-149"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343599","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

Aprepitant mitigates paclitaxel-induced neuropathic pain in rats via suppressing inflammatory pathways in dorsal root ganglia. 阿瑞匹坦通过抑制背根神经节的炎症通路减轻紫杉醇诱发的大鼠神经病理性疼痛

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-13 DOI: 10.1080/01480545.2024.2425992

Mina Khalilzadeh, Moein Ghasemi, Hedyeh Faghir-Ghanesefat, Mahnoosh Ghafouri Esfahani, Ahmad Reza Dehpour, Hamed Shafaroodi

{"title":"Aprepitant mitigates paclitaxel-induced neuropathic pain in rats via suppressing inflammatory pathways in dorsal root ganglia.","authors":"Mina Khalilzadeh, Moein Ghasemi, Hedyeh Faghir-Ghanesefat, Mahnoosh Ghafouri Esfahani, Ahmad Reza Dehpour, Hamed Shafaroodi","doi":"10.1080/01480545.2024.2425992","DOIUrl":"10.1080/01480545.2024.2425992","url":null,"abstract":"Neuropathic pain is the crucial dose-limiting side effect of paclitaxel in chemotherapy patients that negatively impacts the quality of life and survival. Currently, no effective treatment option is available. Aprepitant, a well-established chemotherapy antiemetic performing neurokinin-1 receptor antagonism, shows analgesic effects in some pain models. We studied aprepitant analgesic effects on the paclitaxel-induced neuropathic pain model in rats besides inflammatory markers assessment. Rats intraperitoneally received paclitaxel, reaching the cumulative paclitaxel dose of 8 mg/kg. Aprepitant was orally administered every alternate day between days 2 and 14, with a prescribed dosage of 10 or 20 mg/kg. The evaluation of mechanical allodynia and cold hyperalgesia involved the measurement of paw withdrawal threshold and acetone test score on days 0, 7, and 14. On day 14, paw licking latency was measured using a hot plate test before scarification and tissue collection for interleukin 1β, tumor necrosis factor α, and nuclear factor kappa B (NF-kB) evaluation. Paclitaxel induced neuropathy as indicated by a lowered hind paw withdrawal threshold in the Von Frey test, a higher score in the acetone test, and shortened hot plate latency. Aprepitant effectively alleviated cold and thermal hyperalgesia as well as mechanical allodynia. Moreover, aprepitant administration significantly reversed paclitaxel-mediated elevation of proinflammatory cytokines levels in dorsal root ganglia. In addition, aprepitant application suppressed the protein expression of NF-kB in the dorsal root ganglia of paclitaxel-treated rats, as revealed by western blot analysis. Aprepitant treatment ameliorates neuropathy induced by paclitaxel, which is associated with decreasing proinflammatory cytokines and NF-kB expression.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"62-71"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616653","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

Acute exposure to environmentally relevant concentrations of pharmaceutical pollutants induces neurobehavioral toxicity in zebrafish (Danio rerio). 急性接触环境相关浓度的制药污染物会诱发斑马鱼（Danio rerio）的神经行为毒性。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-07-29 DOI: 10.1080/01480545.2024.2382451

Vasanth Dhakshinamoorthy, S P R Vishali, Sriramakrishnan Elumalai, Ekambaram Perumal

{"title":"Acute exposure to environmentally relevant concentrations of pharmaceutical pollutants induces neurobehavioral toxicity in zebrafish (Danio rerio).","authors":"Vasanth Dhakshinamoorthy, S P R Vishali, Sriramakrishnan Elumalai, Ekambaram Perumal","doi":"10.1080/01480545.2024.2382451","DOIUrl":"10.1080/01480545.2024.2382451","url":null,"abstract":"Pharmaceutical waste from point and non-point sources enters, persists, or disseminates in the environment and is known as environmentally persistent pharmaceutical pollutants. Understanding the impacts of pharmaceutical pollutants on the environment and health is essential. This study investigates the behavioral impacts of pharmaceutical pollutants on aquatic organisms and delineates the possible nexus of oxidative stress. The male zebrafish were exposed to four major representative pharmaceutical pollutants, viz., acetaminophen, carbamazepine, metformin, and trimethoprim at environmentally relevant concentrations individually as well as in a mixture for seven days. Substantial alterations in social interaction, aggressive nature, novel tank exploration, and light and dark zone preferences were recorded and the degree varied to different pharmaceutical pollutants. The activity of oxidative stress markers, superoxide dismutase, glutathione-S-transferase, and catalase, was found to be suppressed to 66-20%, 42-25%, and 59-20% respectively with the elevated malondialdehyde generation (180-260%) compared to control. The activity level of acetylcholine esterase was found to be increased to 200-500% across all treatment groups. Despite the synergistic impacts of pharmaceutical pollutants on the whole system that could not be ascertained, this comprehensive study highlights their toxicity nature to induce neurobehavioral toxicity in zebrafish through oxidative stress mechanisms and altered cholinergic systems.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"37-50"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787554","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

Phytochemical analysis, antioxidant activity and modulatory effect of aqueous leaf extract of Pistacia lentiscus L on oxaliplatin-induced oxidative stress in isolated rat liver mitochondria. Pistacia lentiscus L 的植物化学分析、抗氧化活性和叶水提取物对奥沙利铂诱导的离体大鼠肝线粒体氧化应激的调节作用。

IF 2.1 4区医学

Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1080/01480545.2024.2429615

Nesrine Chouikh, Lamia Benguedouar, Rabha Ayad, Zeineb Medjahed, Andreia Bento-Silva, Noelia Duarte, Mohamed Sifour

{"title":"Phytochemical analysis, antioxidant activity and modulatory effect of aqueous leaf extract of Pistacia lentiscus L on oxaliplatin-induced oxidative stress in isolated rat liver mitochondria.","authors":"Nesrine Chouikh, Lamia Benguedouar, Rabha Ayad, Zeineb Medjahed, Andreia Bento-Silva, Noelia Duarte, Mohamed Sifour","doi":"10.1080/01480545.2024.2429615","DOIUrl":"10.1080/01480545.2024.2429615","url":null,"abstract":"This study evaluates the antioxidant effects of aqueous leaf extract of Pistacia lentiscus (ALEPL) and its potential to counteract oxaliplatin (OXA)-induced mitochondrial oxidative stress in rat livers, a common side effect of chemotherapy in cancer treatment. Bioactive compounds were identified using High-Performance Liquid Chromatography coupled with Tandem Mass Spectrometry (HPLC-MS and MS), with Fourier-Transform Infrared Spectroscopy (FTIR) and Atomic Absorption Spectrophotometry (AAS) for chemical and mineral analysis. ALEPL showed notable antioxidant activity, with IC50 values of 4.30 ± 0.27 μg/mL for DPPH (2,2-Diphenyl-1-picrylhydrazyl) scavenging, 13.64 ± 0.51 μg/mL for reducing power, 32.62 ± 5.32 μg/mL for hydroxyl radical scavenging, and 205.08 ± 25.77 μg/mL for superoxide anion radical scavenging. In ex vivo experiments, mitochondria isolated from Wistar rat livers were treated with OXA and ALEPL in a dose-dependent manner. ALEPL pretreatment effectively restored mitochondrial antioxidant enzyme activities, increased glutathione (GSH) levels, and reduced lipid peroxidation (MDA) caused by OXA. These findings suggest that ALEPL has the potential to act as a natural antioxidant to support cancer treatment by mitigating chemotherapy-induced oxidative stress. Future studies could explore its application as an adjuvant in clinical settings to enhance the efficacy of chemotherapy while reducing its side effects.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"219-230"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738612","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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