Drug and Chemical Toxicology最新文献_第3页

Ginsenoside Rk1 exerts protective effects of LPS-induced podocyte apoptosis and inflammation by inactivating JAK2/STAT3 and NF-κB pathways. 人参皂苷Rk1通过灭活JAK2/STAT3和NF-κB通路，对lps诱导的足细胞凋亡和炎症具有保护作用。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2024-12-29 DOI: 10.1080/01480545.2024.2434900

Xiaohong Ma, Linrong Pang, Feizhuang Shi, Binghe Guan

{"title":"Ginsenoside Rk1 exerts protective effects of LPS-induced podocyte apoptosis and inflammation by inactivating JAK2/STAT3 and NF-κB pathways.","authors":"Xiaohong Ma, Linrong Pang, Feizhuang Shi, Binghe Guan","doi":"10.1080/01480545.2024.2434900","DOIUrl":"10.1080/01480545.2024.2434900","url":null,"abstract":"Podocyte injury is a major biomarker of primary glomerular disease that leads to massive proteinuria and kidney failure. Ginsenoside Rk1, a substance derived from ginseng, has several pharmacological activities, such as anti-apoptotic, anti-inflammatory, and antioxidant effects. In this study, our goal is to investigate the roles and mechanisms of ginsenoside Rk1 in podocyte injury and acute kidney injury (AKI). C57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to mimic AKI-like conditions in vivo. One hour after the LPS challenge, ginsenoside Rk1 (10 mg/kg or 20 mg/kg) or vehicle was orally administered into mice every 6 h until sacrifice at 24 h. Renal functions were assessed by measuring blood urea nitrogen and creatinine. Renal histological changes were examined by hematoxylin and eosin staining. The production of proinflammatory cytokines in kidney tissues was evaluated by RT-qPCR and western blotting. A conditionally immortalized mouse MPC-5 podocyte cell line was treated with LPS and ginsenoside Rk1. Viability and apoptosis of MPC-5 cells were estimated by CCK-8 and flow cytometry. Western blotting was also conducted to measure the protein levels of apoptosis-related and pathway-related genes. The results of abovementioned experiments revealed that Ginsenoside Rk1 ameliorated LPS-stimulated podocyte apoptosis in vitro and relieved renal dysfunctions and inflammatory response in LPS-induced AKI mice. Mechanistically, ginsenoside Rk1 inactivated the JAK2/STAT3 and NF-κB pathways in LPS-treated podocytes and mice. In conclusion, this study shows that Ginsenoside Rk1 attenuates LPS-induced renal dysfunctions and inflammatory response in mice and LPS-induced podocyte apoptosis in vitro through inactivating the NF-κB and JAK2/STAT3 pathways.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1057-1066"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902774","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

Humic acid attenuates cisplatin-induced nephrotoxicity in rats. 腐植酸减轻大鼠顺铂引起的肾毒性。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2025-01-27 DOI: 10.1080/01480545.2025.2453590

Ender Tekes, Meltem Ickin Gulen, Coskun Silan, Aysel Guven Bagla

{"title":"Humic acid attenuates cisplatin-induced nephrotoxicity in rats.","authors":"Ender Tekes, Meltem Ickin Gulen, Coskun Silan, Aysel Guven Bagla","doi":"10.1080/01480545.2025.2453590","DOIUrl":"10.1080/01480545.2025.2453590","url":null,"abstract":"Cisplatin-induced nephrotoxicity, a major limitation of this chemotherapeutic agent, involves oxidative stress, inflammation, and apoptosis. This study investigated the potential renoprotective effects of humic acid in a rat model of cisplatin-induced nephrotoxicity. Forty-two male Wistar rats were assigned to six groups: control, humic acid, cisplatin, cisplatin + humic acid 10 mg/kg, cisplatin + humic acid 20 mg/kg, and cisplatin + humic acid 40 mg/kg. On day 7, the rats were sacrificed, and cardiac blood and kidneys were collected for biochemical and histopathological examinations. Humic acid administration significantly attenuated the cisplatin-induced increases in renal TNF-α and NF-κB levels, indicating a reduction in inflammation. Humic acid also ameliorated histopathological damage, including Bowman's capsule dilatation, tubular cell degeneration, and hemorrhage. However, humic acid did not significantly alter oxidative stress parameters or caspase-3 levels. Humic acid demonstrates a protective effect against cisplatin-induced nephrotoxicity in rats, primarily by mitigating the inflammatory response. While HA's beneficial effects on oxidative stress and apoptosis were limited in this study, its ability to reduce inflammation highlights its potential as a therapeutic strategy to mitigate cisplatin-induced kidney injury.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1132-1140"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051965","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 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub 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":"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":"1121-1131"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","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

Should combined MTX and CoQ10 use be reconsidered in terms of steatosis? A biochemical, flow cytometry, histopathological experimental study. 甲氨蝶呤和辅酶q10联合使用是否应重新考虑脂肪变性？生化、流式细胞术、组织病理学实验研究。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2024-12-29 DOI: 10.1080/01480545.2024.2442660

Ismail Aydin, Zuleyha Erisgin, Esma Cinar, M Zuhal Barak, Yavuz Tekelioglu, Murat Usta, Hasan Serdar Mutlu, Ismail Turkoglu

{"title":"Should combined MTX and CoQ10 use be reconsidered in terms of steatosis? A biochemical, flow cytometry, histopathological experimental study.","authors":"Ismail Aydin, Zuleyha Erisgin, Esma Cinar, M Zuhal Barak, Yavuz Tekelioglu, Murat Usta, Hasan Serdar Mutlu, Ismail Turkoglu","doi":"10.1080/01480545.2024.2442660","DOIUrl":"10.1080/01480545.2024.2442660","url":null,"abstract":"In the present study, the effects of coenzyme Q10 (CoQ10), which is widely used in daily life, on the methotrexate (MTX)-induced hepatotoxicity, which is widely used today in malignancies and autoimmune diseases, were examined. Twenty-four female Wistar albino rats were divided into four groups. The group 1 (n = 6) was given 1 mL corn oil by oral gavage (p.o.) during seven days. Group 2 was given 20 mg/kg intraperitoneal (i.p.) MTX only on the first day of the experiment. Group 3 was given 20 mg/kg (i.p.) MTX on the first day of the experiment and 100 mg/kg CoQ10 dissolved in 1 mL corn oil were given by oral gavage during seven days, and group 4 was given 100 mg/kg CoQ10 dissolved in 1 mL corn oil by oral gavage during seven days. At the end of experiment, all animals were euthanized under anesthesia. In the liver tissue, histopathologic analysis on the hematoxylin and eosin (H&E), Masson trichrome, and periodic acid Schiff (PAS) stained sections, apoptotic analysis (% Annexin V positivity) by flow cytometry, and biochemical analysis for oxidative stress markers (GSH, CAT, and TBARS) was performed. According to histopathological analysis, apoptosis, concession, fibrosis, and inflammatory cell infiltration increased in the MTX group and those results significantly decreased in the MTX + CoQ10 groups. As an interesting result, fatty degeneration and TBARS elevation were observed in the MTX + CoQ10 group. As a result, although CoQ10 has protective effects on MTX-induced hepatotoxicity, fatty degeneration due to the combined usage of MTX and CoQ10 should be investigated with further studies.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1090-1103"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902360","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

Deciphering the genotoxic and cytotoxic properties of teicoplanin: a combined laboratory and computational investigation. 破译替柯planin的基因毒性和细胞毒性：一项联合实验室和计算研究。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2025-05-08 DOI: 10.1080/01480545.2025.2502446

Ahmet Ali Berber, Işıl Deniz Aliravci, Nihan Akinci Kenanoğlu, Şefika Nur Demir

{"title":"Deciphering the genotoxic and cytotoxic properties of teicoplanin: a combined laboratory and computational investigation.","authors":"Ahmet Ali Berber, Işıl Deniz Aliravci, Nihan Akinci Kenanoğlu, Şefika Nur Demir","doi":"10.1080/01480545.2025.2502446","DOIUrl":"10.1080/01480545.2025.2502446","url":null,"abstract":"In this study, the mutagenicity and carcinogenicity of the teicoplanin antibiotic were first investigated using the Vega Hub and Toxtree software through in silico prediction. The cytotoxic and genotoxic effects were evaluated using in vitro assays, including the mitotic index (MI), micronucleus (MN), nuclear division index (NDI), and Comet Assay (CA) in human lymphocytes. In the in vitro studies, both 24-hour and 48-hour exposures were conducted for MI, and teicoplanin significantly decreased MI compared to the control at all concentrations. In addition, a significant increase was detected in the MN frequency compared to the negative control at all concentrations. In the Comet assay, tail length significantly increased compared to the control at all concentrations except for 5.6 µg/mL, while tail moment and comet tail intensity significantly increased at all concentrations compared to the control. In conclusion, within the concentration range used in this study, teicoplanin was found to have cytotoxic and genotoxic effects.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1015-1024"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988361","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

Computational investigation of m-acetamide and 3MPAEA: Characterization, toxicity, and molecular docking and dynamic analyses. 间乙酰胺和3MPAEA的计算研究：表征、毒性、分子对接和动力学分析。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2025-04-28 DOI: 10.1080/01480545.2025.2496358

Nevin Çankaya, Mehmet Hanifi Kebiroğlu, Serap Yalcin Azarkan

{"title":"Computational investigation of m-acetamide and 3MPAEA: Characterization, toxicity, and molecular docking and dynamic analyses.","authors":"Nevin Çankaya, Mehmet Hanifi Kebiroğlu, Serap Yalcin Azarkan","doi":"10.1080/01480545.2025.2496358","DOIUrl":"10.1080/01480545.2025.2496358","url":null,"abstract":"In this study, 2-(3-methoxyphenylamino)-2-oxoethyl acrylate (3MPAEA) molecule was synthesized in two steps. In the first step, 2-chloro-N-(3-methoxyphenyl)acetamide (m-acetamide) was obtained. Density functional theory (DFT) calculations were performed to obtain information about the electronic and structural properties of the synthesized molecules. The Raman Spectrum and UV-Visible analysis were calculated using the Gaussian package program. Additionally, Natural Bond Orbital (NBO) Analysis, Electron Localization Function (ELF), Electrostatic Potential Map (ESP), Average Local Ionization Energy (ALIE), and the toxicological properties of the molecules were examined. Simultaneously, molecular docking and dynamic analyses were conducted to investigate the interaction of m-acetamide and 3MPAEA with proteins involved in nuclear receptor signaling pathways, stress response pathways, molecular initiating events, and metabolism, as identified in the protox analysis. The findings aligned with the protox analysis results. The results obtained provide new insights into the electronic and toxicological properties of these molecules.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"943-958"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971604","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

Molecular docking, ADME properties and synthesis of thiophene sulfonamide derivatives. 噻吩磺酰胺衍生物的分子对接、ADME 特性和合成。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2024-11-13 DOI: 10.1080/01480545.2024.2417963

Jesurajan Jebamani, Jayadev Shivalingappa, Shubha Pranesh, Mussuvir Pasha, Chandrakant Pawar

{"title":"Molecular docking, ADME properties and synthesis of thiophene sulfonamide derivatives.","authors":"Jesurajan Jebamani, Jayadev Shivalingappa, Shubha Pranesh, Mussuvir Pasha, Chandrakant Pawar","doi":"10.1080/01480545.2024.2417963","DOIUrl":"10.1080/01480545.2024.2417963","url":null,"abstract":"This study investigates the drug-like properties of target molecules containing thiophene sulfonamide groups (7a-7s) using computational molecular docking techniques. The binding interactions of these derivatives were assessed using protein 2NSD (Enoyl acyl carrier protein reductase InhA, complexed with N-(4-methylbenzoyl)-4-benzylpiperidine, PDB DOI: 10.2210/pdb2NSD/pdb) as the receptor. Molecular docking results revealed notable docking scores for all compounds, ranging from -6 to -12 kcal/mol. Compounds 7e, 7i, and 7f, in particular, demonstrated impressive glide scores (>11 kcal/mol) and were selected for further analysis through molecular dynamics simulations, which provided deeper insights into their dynamic behavior and stability. The drug-like properties of these molecules were evaluated based on Lipinski's Rule of Five and ADME (Absorption, Distribution, Metabolism, and Excretion) criteria and compared with known drugs. Additionally, we synthesized these target molecules (7a-7s) using Suzuki-Miyaura coupling with a nickel catalyst replacing palladium. The chemical structures of the synthesized compounds were confirmed through elemental analysis, LC-MS,1H-NMR, and 13C-NMR spectroscopy.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"923-942"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616675","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

Pre-clinical acute oral toxicity and subacute neurotoxicity risk assessments on sprague dawley rats treated with single dose or repeated doses of flavonoid-enriched fraction extracted from Oroxylum indicum leaves. 单次或多次给药富黄酮提取物对大鼠临床前急性口腔毒性和亚急性神经毒性的影响

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2025-01-30 DOI: 10.1080/01480545.2024.2449210

Farah Amna Othman, Anani Aila Mat Zin, Yusmazura Zakaria, Nik Nur Hakimah Nik Salleh, Asmaa' Mohd Satar, Suat Cheng Tan

{"title":"Pre-clinical acute oral toxicity and subacute neurotoxicity risk assessments on sprague dawley rats treated with single dose or repeated doses of flavonoid-enriched fraction extracted from Oroxylum indicum leaves.","authors":"Farah Amna Othman, Anani Aila Mat Zin, Yusmazura Zakaria, Nik Nur Hakimah Nik Salleh, Asmaa' Mohd Satar, Suat Cheng Tan","doi":"10.1080/01480545.2024.2449210","DOIUrl":"10.1080/01480545.2024.2449210","url":null,"abstract":"Oroxylum indicum possesses promising flavonoid secondary metabolites. However, translation of these compounds into clinical practice for neurological disease treatment is halted as the toxicity and safety profile of the plant extracts are yet to be determined. This study was conducted to assess the acute oral toxicity and subacute neurotoxicity that could be imposed by the flavonoid-enriched fraction (FEF) extracted from O. indicum leaves, by strictly following the procedures set in Organization for Economic Co-operation and Development (OECD) Guidelines No.420 and 424. It was found that at the highest dosage (2000 mg/kg b.wt), no death or toxicity-related behavioral changes were observed. No significant alteration in hematological and serum biochemical parameters beyond the standard laboratory range was observed. Detailed histopathological examination, as verified by clinical pathologist, revealed absence of detectable inflammation, changes in any macroscopic and microscopic tissue abnormalities in all vital organ of the treated rats. Moreover, neurological functional test of rats treated with repeated doses of FEF for 28 d also showed absence of neurological abnormality, suggesting negative long term side effects of this fraction on the animal. In conclusion, this study presented valuable pre-clinical safety validation of a high-quality herbal medicinal product, setting the foundation for its future application in clinical setting.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1104-1120"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064472","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

Introduced paeoniflorin reduces the main toxicity induced by diosbulbin B, the major toxic compound of Dioscorea bulbifera L.: involved inhibiting inflammation and ferroptosis. 引入芍药苷降低了黄药苷B的主要毒性作用，黄药苷B是黄药苷的主要毒性成分，主要参与抑制炎症和铁凋亡。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2024-12-16 DOI: 10.1080/01480545.2024.2440451

Tianzhu Zhang, Bingyin Li, Junming Wang, Xiaohui Wu, Lingling Song, Yanmei Wang, Yueyue Zhang, Yamin Li

{"title":"Introduced paeoniflorin reduces the main toxicity induced by diosbulbin B, the major toxic compound of Dioscorea bulbifera L.: involved inhibiting inflammation and ferroptosis.","authors":"Tianzhu Zhang, Bingyin Li, Junming Wang, Xiaohui Wu, Lingling Song, Yanmei Wang, Yueyue Zhang, Yamin Li","doi":"10.1080/01480545.2024.2440451","DOIUrl":"10.1080/01480545.2024.2440451","url":null,"abstract":"Rhizoma Dioscoreae Bulbiferae (HYZ) is a widely utilized herb in clinical practice, known for its significant biological activities. However, the associated hepatotoxicity poses limitations to its application. Our previous research indicated that the effective mitigation of HYZ-induced hepatotoxicity through the concoction with Radix Paeoniae Alba medicinal juice involves the incorporation of paeoniflorin (Pae) and a reduction in diosbulbin B (DB), the primary toxic compound in HYZ. This finding suggests that the introduced Pae may exert a direct attenuating effect on DB. In light of this, this study represents the first investigation into Pae's detoxification effect against DB-induced hepatotoxicity after administration for 2 months in mice vivo while also exploring underlying mechanisms related to inflammation and ferroptosis based on network pharmacology results. Our findings demonstrate that Pae significantly alleviates DB-induced hepatotoxicity in a dose-dependent manner. Western blotting and ELISA analyses revealed that Pae effectively reversed elevated levels of hepatic inflammation-related markers-such as NF-κB, p38 MAPK, NLRP3, TNF-α, and IL-1β-as well as excessively high concentrations of ferroptosis-related MDA and Fe2+. Furthermore, it restored low levels of GSH, SOD, GPX4, and FTH1. In summary, introduced Pae substantially mitigated DB-induced hepatotoxicity by inhibiting both hepatocyte inflammation and ferroptosis.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1080-1089"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834587","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

Linolenic acid stimulates eryptosis and hemolysis through oxidative stress and CK1α/MLKL: protective role of melatonin, urea, and polyethylene glycol. 亚麻酸通过氧化应激和 CK1α/MLKL 刺激红细胞增多症和溶血：褪黑激素、尿素和聚乙二醇的保护作用。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-09-01 Epub Date: 2024-10-31 DOI: 10.1080/01480545.2024.2420680

Feryal H Alharthy, Jawaher Alsughayyir, Mohammad A Alfhili

{"title":"Linolenic acid stimulates eryptosis and hemolysis through oxidative stress and CK1α/MLKL: protective role of melatonin, urea, and polyethylene glycol.","authors":"Feryal H Alharthy, Jawaher Alsughayyir, Mohammad A Alfhili","doi":"10.1080/01480545.2024.2420680","DOIUrl":"10.1080/01480545.2024.2420680","url":null,"abstract":"Anticancer medications cause anemia in patients through ill-defined mechanisms, including hemolysis and eryptosis. Although α-linolenic acid (ALA) possesses anticancer properties against a variety of cancer cells, there is a dearth of evidence regarding how it modulates red blood cell (RBC) physiology. RBCs from healthy donors were subjected to anticancer concentrations of ALA (2.5, 5, 10, 20, 40, 80, and 100 μM) at 37 °C for 24 h, and colorimetric tests were used to determine hemolysis and acetylcholinesterase (AChE) activity. Meanwhile, flow cytometry was employed to identify eryptotic cells using annexin-V-FITC and forward scatter (FSC), Fluo4/AM to detect Ca2+, and H2DCFDA to assess oxidative stress. ALA significantly increased hemolysis and eryptosis in a concentration-dependent manner, along with elevated Fluo4 and DCF fluorescence, and erythrocyte sedimentation rate, and reduced FSC and AChE activity. Moreover, the addition of D4476, necrosulfonamide, melatonin, isosmotic urea, and polyethylene glycol 8000 - but not sucrose - significantly inhibited ALA toxicity. In conclusion, ALA stimulates hemolysis and eryptosis through Ca2+ buildup, oxidative stress, anticholinesterase activity, casein kinase 1α (CK1α), and mixed lineage kinase domain-like protein (MLKL). The anticancer activity of ALA may be potentiated by the use of Ca2+ channel blockers and chelators, antioxidants, and CK1α and MLKL inhibitors to ameliorate its toxicity to RBCs.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"912-922"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544355","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