Drug and Chemical Toxicology最新文献

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Borax attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/ROS balance in acrylamide-induced neurotoxicity in rainbow trout. 硼砂在丙烯酰胺诱导的虹鳟神经毒性中通过调节Nrf2/ROS平衡减轻氧化应激、炎症和细胞凋亡
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-06-28 DOI: 10.1080/01480545.2024.2370916
Hasan Turkez, Gonca Alak, Fatma Betul Ozgeris, Aslı Cilingir Yeltekin, Arzu Ucar, Veysel Parlak, Nicoleta Anca Şuţan, Muhammed Atamanalp
{"title":"Borax attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/ROS balance in acrylamide-induced neurotoxicity in rainbow trout.","authors":"Hasan Turkez, Gonca Alak, Fatma Betul Ozgeris, Aslı Cilingir Yeltekin, Arzu Ucar, Veysel Parlak, Nicoleta Anca Şuţan, Muhammed Atamanalp","doi":"10.1080/01480545.2024.2370916","DOIUrl":"10.1080/01480545.2024.2370916","url":null,"abstract":"<p><p>Acrylamide (ACR) can have adverse environmental effects because of its multiple applications. Relevant scientific literatures of the existence of ACR residues in foods following processing steps have raised concern in the biochemistry, chemistry and safety of this vinyl substance. The interest has focused on the hepatotoxicity of ACR in animals and humans and on the ACR content mitigation and its detoxification. Borax (BX), as a naturally occurring antioxidant featured boron compound, was selected in this investigation to assess its possible neuro-protective potential against ACR-induced neurotoxicity. Nrf2 axis signaling pathways and detoxification response to oxidative stress after exposure to ACR in brains of rainbow trout, and the effect of BX application on reducing ACR-induced neurotoxicity were investigated. Rainbow trout were acutely exposed to ACR (12.5 mg/L) alone or simultaneously treated with BX (0.75 mg/L) during 96h. The exposed fish were sampled at 48th and 96th and oxidative stress response endpoints, 8-OHdG, Nrf2, TNF-α, caspase-3, in addition to IL-6 activities and the levels of AChE and BDNF in brain tissues of rainbow trout (<i>Oncorhynchus mykiss</i>) were evaluated. Samples showed decreases in the levels of ACR-mediated biomarkers used to assess neural toxicity (SOD, CAT, GPx, AChE, BDNF, GSH), increased levels of MDA, MPO, DNA damage and apoptosis. ACR disrupted the Nrf2 pathway, and induced neurotoxicity. Inhibited activities' expressions under simultaneous administration experiments, revealed the protective effects of BX against ACR-induced toxicity damage. The obtained data allow the outline of early multi-parameter signaling pathways in rainbow trout.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"27-36"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466881","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
Construction of an explanatory model for predicting hepatotoxicity: a case study of the potentially hepatotoxic components of Gardenia jasminoides. 构建预测肝毒性的解释性模型:栀子中潜在肝毒性成分的案例研究。
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-06-28 DOI: 10.1080/01480545.2024.2364905
Qi Yang, Lili Fan, Erwei Hao, Xiaotao Hou, Jiagang Deng, Zhengcai Du, Zhongshang Xia
{"title":"Construction of an explanatory model for predicting hepatotoxicity: a case study of the potentially hepatotoxic components of <i>Gardenia jasminoides</i>.","authors":"Qi Yang, Lili Fan, Erwei Hao, Xiaotao Hou, Jiagang Deng, Zhengcai Du, Zhongshang Xia","doi":"10.1080/01480545.2024.2364905","DOIUrl":"10.1080/01480545.2024.2364905","url":null,"abstract":"<p><p>It is well-known that the hepatotoxicity of drugs can significantly influence their clinical use. Despite their effective therapeutic efficacy, many drugs are severely limited in clinical applications due to significant hepatotoxicity. In response, researchers have created several machine learning-based hepatotoxicity prediction models for use in drug discovery and development. Researchers aim to predict the potential hepatotoxicity of drugs to enhance their utility. However, current hepatotoxicity prediction models often suffer from being unverified, and they fail to capture the detailed toxicological structures of predicted hepatotoxic compounds. Using the 56 chemical constituents of <i>Gardenia jasminoides</i> as examples, we validated the trained hepatotoxicity prediction model through literature reviews, principal component analysis (PCA), and structural comparison methods. Ultimately, we successfully developed a model with strong predictive performance and conducted visual validation. Interestingly, we discovered that the predicted hepatotoxic chemical constituents of Gardenia possess both toxic and therapeutic effects, which are likely dose-dependent. This discovery greatly contributes to our understanding of the dual nature of drug-induced hepatotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"107-119"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466882","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 ameliorative effect of methanol extract of Ricinodendron heudelotii (Baill.) leaves on paracetamol-induced hepatotoxicity in Wistar rats. Ricinodendron heudelotii (Baill.) 叶甲醇提取物对扑热息痛诱导的 Wistar 大鼠肝毒性的改善作用。
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-06-05 DOI: 10.1080/01480545.2024.2362891
Great Iruoghene Edo, Favour Ogheneoruese Onoharigho, Agatha Ngukuran Jikah, Joy Johnson Agbo
{"title":"The ameliorative effect of methanol extract of <i>Ricinodendron heudelotii (Baill.)</i> leaves on paracetamol-induced hepatotoxicity in Wistar rats.","authors":"Great Iruoghene Edo, Favour Ogheneoruese Onoharigho, Agatha Ngukuran Jikah, Joy Johnson Agbo","doi":"10.1080/01480545.2024.2362891","DOIUrl":"10.1080/01480545.2024.2362891","url":null,"abstract":"<p><p>Plants are a rich source of antioxidants that are produced naturally. Therefore, this study was aimed to evaluate the effect of the plant <i>Ricinodendron heudelotii (Baill.)</i> in the attenuation of paracetamol (PCM) hepatotoxicity in Wistar rats. Twenty-four male albino Wistar rats weighing between 200 and 250 g were divided into four groups, with six rats each. Group 1 served as the control group, receiving just distilled water. Groups 2 and 3 received orally 250 mg/kg bwt/day PCM and 300 mg/kg bwt/day methanol extract of <i>Ricinodendron heudelotii (Baill.)</i> leaves for two weeks, respectively. For group 4, the <i>Ricinodendron heudelotii (Baill.)</i> leaf extract was pre-administered for 1 week before receiving 300 mg/kg bwt/day <i>Ricinodendron heudelotii (Baill.)</i> leaves extract and 250 mg/kg bwt/day PCM for 2 weeks. As a marker of liver damage, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue reduced glutathione (GSH) concentration, superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase activities were utilized to determine antioxidant state, while malondialdehyde (MDA) concentration was employed as a lipid peroxidation indicator. When compared to the control group, the activities of serum AST, ALT, SOD, and MDA levels were considerably (<i>p</i> < 0.05) higher in the PCM group, although GSH level and GST and catalase activities were significantly lower. In comparison to the PCM group, co-administration of PCM with <i>Ricinodendron heudelotii (Baill.)</i> extract decreased serum AST and ALT activities. This study shows that the leaf extracts of <i>Ricinodendron heudelotii (Baill.)</i> protects Wistar rats' livers from PCM-induced oxidative stress by increasing antioxidant enzymes.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"98-106"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261416","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
Assessment of the effect of sodium tetraborate on oxidative stress, inflammation, and apoptosis in lead-induced nephrotoxicity. 评估四硼酸钠对铅诱导的肾毒性中氧化应激、炎症和细胞凋亡的影响。
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-05-28 DOI: 10.1080/01480545.2024.2358067
Turan Yaman, H Turan Akkoyun, Mahire Bayramoğlu Akkoyun, Fatma Karagözoğlu, Şule Melek, Ömer Faruk Keleş, Aydın Şükrü Bengü
{"title":"Assessment of the effect of sodium tetraborate on oxidative stress, inflammation, and apoptosis in lead-induced nephrotoxicity.","authors":"Turan Yaman, H Turan Akkoyun, Mahire Bayramoğlu Akkoyun, Fatma Karagözoğlu, Şule Melek, Ömer Faruk Keleş, Aydın Şükrü Bengü","doi":"10.1080/01480545.2024.2358067","DOIUrl":"10.1080/01480545.2024.2358067","url":null,"abstract":"<p><p>Exposure to Pb, a toxic heavy metal, is a risk factor for renal damage. Borax, an essential trace element in cellular metabolism, is a naturally occurring compound found in many foods. This study investigated the effects of sodium tetraborate (ST), a source of borax, on renal oxidative stress and inflammation in rats exposed to Pb. Wistar Albino rats (n = 24) were divided into four groups: Control (0.5 mL, i.p. isotonic), Pb (50 mg/kg/day/i.p.), ST (4.0 mg/kg/day/oral), and Pb + ST groups. At the end of the five-day experimental period, kidney tissue samples were obtained and analyzed. Histopathologically, the Pb-induced damage observed in the Pb group improved in the Pb + ST group. Immunohistochemically, Pb administration increased the expression of inducible nitric oxide synthase, cyclooxygenase-2, and caspase-3. When evaluated biochemically, Pb application inhibited catalase and glutathione peroxidase (GSH-Px) enzyme activities and activated superoxide dismutase enzyme activity. An increase in malondialdehyde levels was considered an indicator of damage. ST application increases glutathione peroxidase enzyme activity and decreased malondialdehyde levels. These results indicate that ST might play a protective role against Pb-induced renal damage via the upregulation of renal tissue antioxidants and cyclooxygenase-2, inducible nitric oxide synthase, and caspase-3 immunoexpression.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"150-162"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156786","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 injury induced by triclopyr in the rat liver. 三氯吡啶对大鼠肝脏线粒体的损伤
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-06-11 DOI: 10.1080/01480545.2024.2362888
J S Rizzi, D G Seloto, L C Pereira
{"title":"Mitochondrial injury induced by triclopyr in the rat liver.","authors":"J S Rizzi, D G Seloto, L C Pereira","doi":"10.1080/01480545.2024.2362888","DOIUrl":"10.1080/01480545.2024.2362888","url":null,"abstract":"<p><p>The herbicide triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) is already considered an environmental problem due to damage caused by incorrect disposal, leaching, and aerial dispersion, which may pose risks to the environment and human health. Studies have evaluated metabolism, absorption, excretion, and active transport but there is no clear information about its mode of action (MoA) and its cytotoxic action potential remains unknown. In this context, mitochondria have been used to assess the toxicity of xenobiotics, for this reason, to identify the toxic mechanism of triclopyr, hepatic mitochondria from Wistar rats were exposed <i>in vitro</i> to different concentrations of triclopyr (0.5-500 µM). There was neither formation/accumulation of reactive oxygen and nitrogen species, nor lipid peroxidation or changes in the mitochondrial antioxidant system, in addition to proper functioning of oxidative phosphorylation and ATP production. Changes were found in NAD(P)H oxidation, membrane potential dissipation and mitochondrial calcium gradient. These results demonstrate that mitochondria suffer damage related to their bioenergetics and redox status but not to their structure when exposed to concentrations of triclopyr considered higher than those described as found in the environment so far.HighlightsTriclopyr has a low mitochondrial uncoupling potential.The damage caused to the bioenergetics and redox state of the mitochondria is related to concentrations considered higher than those found in the environment.Even at high concentrations, triclopyr was not able to change the structure of the organelle after exposure.Oxidative phosphorylation and ATP production were not impaired after exposure.NAD(P)H oxidation resulted in potential membrane dissipation and mitochondrial calcium gradient dissipation.Triclopyr does not have RONS-forming properties, as well as it does not peroxide membrane lipids, it preserves membrane sulfhydryl groups and maintains the normality of the GSH/GSSG ratio.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"187-198"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300361","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
Assessment of morin hydrate as a renal protective agent in rats subjected to methotrexate-induced nephrotoxicity. 评估水合吗啉作为一种肾脏保护剂对甲氨蝶呤诱导的肾毒性大鼠的作用。
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1080/01480545.2024.2429616
Ekrem Darendelioğlu, Sevda Sağ, Cuneyt Caglayan
{"title":"Assessment of morin hydrate as a renal protective agent in rats subjected to methotrexate-induced nephrotoxicity.","authors":"Ekrem Darendelioğlu, Sevda Sağ, Cuneyt Caglayan","doi":"10.1080/01480545.2024.2429616","DOIUrl":"10.1080/01480545.2024.2429616","url":null,"abstract":"<p><p>Methotrexate (MTX) is a generally applied chemotherapeutic medicine in most cancers treatment. Morin hydrate, a robust antioxidant, is a secondary metabolite observed in numerous plants, along with figs, white mulberries, and others. The hypothesis of this study is that morin hydrate can effectively reduce MTX-induced kidney injury in rats by increasing antioxidant enzyme activity and inhibiting apoptotic processes. This study, 35 male Wistar albino rats were used, and five different experimental groups, each consisting of 7 rats were established. Group 1 served as the control group while Group 2 received morin exclusively via oral administration (at a dose of 100 mg/kg). Group 3, however, was administered MTX exclusively (at a dose of 20 mg/kg). Group 4 received a combination of MTX (20 mg/kg) and morin (50 mg/kg), and Group 5 received a combination of MTX (20 mg/kg) and morin (100 mg/kg). The MTX group showed a significant increase in kidney biomarkers, including serum urea, creatinine, and the lipid peroxidation biomarker MDA, compared to the control group, along with a notable decrease in antioxidant enzyme activity (SOD, CAT, GPx) and GSH levels. Furthermore, MTX notably decreased the expression of procas-3, Bcl-2, procas-9, and procas-8 while concurrently increasing the expression of apoptotic genes such as CYT-C and Bax. Co-administration of morin hydrate with MTX at doses of 50 and 100 mg/kg effectively managed oxidative damage levels and apoptotic markers, demonstrating antioxidant and anti-apoptotic properties. Notably, the 100 mg/kg dose provided more robust protection than the 50 mg/kg dose, indicating a dose-dependent efficacy. This investigation thus supports the conclusion that morin hydrate, at both dosage levels, effectively mitigates MTX-induced renal damage.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"172-179"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738791","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
Mechanistic insight into the hepatoprotective effect of Moringa oleifera Lam leaf extract and telmisartan against carbon tetrachloride-induced liver fibrosis: plausible roles of TGF-β1/SMAD3/SMAD7 and HDAC2/NF-κB/PPARγ pathways. 从机理上揭示油杉叶提取物和替米沙坦对四氯化碳诱导的肝纤维化的保护作用:TGF-β1/SMAD3/SMAD7 和 HDAC2/NF-κB/PPARγ 通路的合理作用。
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-06-04 DOI: 10.1080/01480545.2024.2358066
Nayira A Abdel Baky, Lamiaa M Fouad, Kawkab A Ahmed, Amany A Alzokaky
{"title":"Mechanistic insight into the hepatoprotective effect of <i>Moringa oleifera</i> Lam leaf extract and telmisartan against carbon tetrachloride-induced liver fibrosis: plausible roles of TGF-β1/SMAD3/SMAD7 and HDAC2/NF-κB/PPARγ pathways.","authors":"Nayira A Abdel Baky, Lamiaa M Fouad, Kawkab A Ahmed, Amany A Alzokaky","doi":"10.1080/01480545.2024.2358066","DOIUrl":"10.1080/01480545.2024.2358066","url":null,"abstract":"<p><p>The increasing prevalence and limited therapeutic options for liver fibrosis necessitates more medical attention. Our study aims to investigate the potential molecular targets by which <i>Moringa oleifera</i> Lam leaf extract (Mor) and/or telmisartan (Telm) alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 (1 ml/kg) every 72 hours, for 8 weeks. Intoxicated rats with CCl4 were simultaneously orally administrated Mor (400 mg/kg/day for 8 weeks) and/or Telm (10 mg/kg/day for 8 weeks). Treatment of CCl4-intoxicated rats with Mor/Telm significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to CCl4 intoxicated group (P < 0.001). Additionally, Mor/Telm treatment significantly reduced the level of hepatic inflammatory, profibrotic, and apoptotic markers including; nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-βeta1 (TGF-β1), and caspase-3. Interestingly, co-treatment of CCl4-intoxicated rats with Mor/Telm downregulated m-RNA expression of histone deacetylase 2 (HDAC2) (71.8%), and reduced protein expression of mothers against decapentaplegic homolog 3 (p-SMAD3) (70.6%) compared to untreated animals. Mor/Telm regimen also elevated p-SMAD7 protein expression as well as m-RNA expression of peroxisome proliferator-activated receptor γ (PPARγ) (3.6 and 3.1 fold, respectively p < 0.05) compared to CCl4 intoxicated group. Histopathological picture of the liver tissue intoxicated with CCl4 revealed marked improvement by Mor/Telm co-treatment. Conclusively, this study substantiated the hepatoprotective effect of Mor/Telm regimen against CCl4-induced liver fibrosis through suppression of TGF-β1/SMAD3, and HDAC2/NF-κB signaling pathways and up-regulation of SMAD7 and PPARγ expression.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"84-97"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247632","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
Neuroprotective effects of fermented blueberry and black rice against particulate matter 2.5 μm-induced inflammation in vitro and in vivo. 发酵蓝莓和黑米对微粒物质 2.5 μm 诱导的体外和体内炎症的神经保护作用
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-07-22 DOI: 10.1080/01480545.2024.2367559
Al Borhan Bayazid, Soo Ah Jeong, Shofiul Azam, Seung Hyeon Oh, Beong Ou Lim
{"title":"Neuroprotective effects of fermented blueberry and black rice against particulate matter 2.5 μm-induced inflammation <i>in vitro</i> and <i>in vivo</i>.","authors":"Al Borhan Bayazid, Soo Ah Jeong, Shofiul Azam, Seung Hyeon Oh, Beong Ou Lim","doi":"10.1080/01480545.2024.2367559","DOIUrl":"10.1080/01480545.2024.2367559","url":null,"abstract":"<p><p>The increasing prevalence of particulate matter (PM) has raised significant concerns about its adverse effects on human health. This study investigates the potential of fermented blueberry and black rice (FBBR) in mitigating the effects of PM2.5 in SH-SY5Y cells and mice. Various assays, including MTT, NO, western blot, ELISA, and behavioral studies were conducted. Results showed that PM2.5 induced considerable cytotoxicity and elevated NO production at a concentration of 100 μg/mL of PM2.5 in SH-SY5Y cells. FBBR administration attenuated PM2.5-exposed cytotoxicity and suppressed NO production in SH-SY5Y cells. In an intranasally-exposed mice model, 10 mg/kg body weight (BW) of PM2.5 resulted in cognitive impairments. However, FBBR treatment ameliorated these impairments in both the Y-maze and MWM tests in PM2.5-exposed mice. Additionally, FBBR administration increased the expression of BDNF and reduced inflammatory markers in the brains of PM2.5-exposed SH-SY5Y cells. These findings highlight the detrimental effects of PM2.5 on the nervous system and suggest the potential of FBBR as a nutraceutical agent for mitigating these effects. Importantly, the results emphasize the urgency of addressing the harmful impact of PM2.5 on the nervous system and underscore the promising role of FBBR as a protective intervention against the adverse effects associated with PM2.5 exposure.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"16-26"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733793","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
Unraveling the hepatoprotective and anti-pancreatic cancer potential of Caralluma europaea: a comprehensive in vivo, in vitro and in silico evidence. 揭示欧石榴的保肝和抗胰腺癌潜力:体内、体外和硅学综合证据
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-10-17 DOI: 10.1080/01480545.2024.2402430
Fatima Ez-Zahra Amrati, Adrian Lim, Meryem Slighoua, Mohamed Chebaibi, Ibrahim Mssillou, Aziz Drioiche, Francesca Di Cristo, Yazeed A Al-Sheikh, Mourad A M Aboul-Soud, Mouad Edderkaoui, Dalila Bousta
{"title":"Unraveling the hepatoprotective and anti-pancreatic cancer potential of <i>Caralluma europaea</i>: a comprehensive <i>in vivo, in vitro</i> and in silico evidence.","authors":"Fatima Ez-Zahra Amrati, Adrian Lim, Meryem Slighoua, Mohamed Chebaibi, Ibrahim Mssillou, Aziz Drioiche, Francesca Di Cristo, Yazeed A Al-Sheikh, Mourad A M Aboul-Soud, Mouad Edderkaoui, Dalila Bousta","doi":"10.1080/01480545.2024.2402430","DOIUrl":"10.1080/01480545.2024.2402430","url":null,"abstract":"<p><p><i>Caralluma europaea</i> Guss. (<i>C. europaea</i>) is a medicinal plant used for cancer treatment. However, these treatments may be associated with complications that need to be investigated. This work aims to evaluate not only the chemical composition but also the hepatoprotective and anticancer properties of <i>C. europaea</i> extracts. The chemical constitution of the hydroethanolic extract was explored using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The hydroethanolic extract, flavonoids, and polyphenols-rich extract at 100, 15, and 50 mg/kg, respectively, were administered to acetaminophen-treated rats for seven days. We used Western blotting and Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) to determine the protein and the mRNA levels of cancer stemness markers in pancreatic cancer cell lines MIA PaCa-2 and BxPC-3 exposed to increasing doses of <i>C. europaea</i> extracts. <i>In silico</i> analysis was used to evaluate the effects of phenolic compounds revealed in <i>C. europaea</i> on caspase-3 and HSP90, and on liver damage on CYP2E1. The primary phenolics detected by GC-MS and HPLC were ferulic acid and benzofurazan. The positive control group showed an increase in AST, ALT, ALP, triglycerides, and VLDL levels. <i>C. europaea</i> extracts demonstrated hepatoprotective effects by ameliorating acetaminophen-induced alterations of biochemical and hispathological parameters. Immunoblotting and RT-qPCR profiling of cancer stemness markers indicated a reduction in the expression levels of Oct-4 and Nanog proteins, as well as a reduction in the mRNA levels of CD133 by 50-60% and Sox2 by 80-90% in pancreatic cancer cells. Molecular docking showed that naringenin presented the highest docking Gscore on CYP2E1 (-8.199) and HSP90 (-7.742). In conclusion, <i>C. europaea</i> extracts could be considered as a safe and promising therapeutic strategy to sensitize pancreatic cancer cells to chemotherapy.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"120-135"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460515","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
Effect of lycopene on TiO2 nanoforms induced oxidative stress and neuroinflammation in SH-SY5Y cells: an in vitro study. 番茄红素对二氧化钛纳米诱导的 SH-SY5Y 细胞氧化应激和神经炎症的影响:一项体外研究。
IF 2.1 4区 医学
Drug and Chemical Toxicology Pub Date : 2025-01-01 Epub Date: 2024-09-03 DOI: 10.1080/01480545.2024.2397429
Rafa Almeer, Nouf M Alyami
{"title":"Effect of lycopene on TiO<sub>2</sub> nanoforms induced oxidative stress and neuroinflammation in SH-SY5Y cells: an <i>in vitro</i> study.","authors":"Rafa Almeer, Nouf M Alyami","doi":"10.1080/01480545.2024.2397429","DOIUrl":"10.1080/01480545.2024.2397429","url":null,"abstract":"<p><p>Due to its antioxidant action, the carotenoid lycopene has been demonstrated to have a protective effect in several disease models; however, its effect on the nanoform of titanium oxide (nano-TiO<sub>2</sub>)-induced neurotoxicity has not yet been determined. The purpose of this study was to evaluate how lycopene affects neuronal damage brought on by nano-TiO<sub>2</sub> and the mechanisms involved. SH-SY5Y cells were treated with different concentrations of nano-TiO<sub>2</sub> for 48 hours, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used after that to evaluate cell viability. IC<sub>50</sub> of nano-TiO<sub>2</sub> was determined and the results revealed that IC<sub>50</sub> is equal 40 µM/mL, lycopene (10 µM) was applied to SH-SY5Y human neuroblastoma cells an hour before exposure to 40 µM nano-TiO<sub>2</sub>. Reactive oxygen species, lipid peroxidation, nitric oxide, glutathione, superoxide dismutase, and catalase, tumor necrosis factor-alpha, interleukin 1 beta, nuclear factor kappa B, and apoptotic markers (Bcl2, Bax, and caspase-3), were measured to determine the anti-oxidant effect of lycopene. In SH-SY5Y neuroblastoma cells, pretreatment with 10 µM lycopene significantly reduced the toxicity brought on by exposure to nano-TiO<sub>2</sub>, according to MTT assay findings and lactate dehydrogenase (LDH) cytotoxicity assessment. In cells exposed to nano-TiO<sub>2</sub>, lycopene pretreatment significantly boosted the activity of antioxidative enzymes and reduced oxidative stress. Furthermore, when SH-SY5Y cells were subjected to nano-TiO<sub>2</sub>, lycopene pretreatment stopped neuroinflammation and apoptosis. The findings of this study suggest that lycopene may be an effective neuroprotective against oxidative stress and neuroinflammation and may be used to stop neuronal death or injury in a variety of neurological illnesses.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"51-61"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125145","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
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