Drug and Chemical Toxicology最新文献_第3页

Determination of a cytotoxicity threshold for α-Fe₂O₃ nanoparticles based on an in vitro-in vivo dosimetry model in alveolar epithelial cells. α-Fe2O3纳米颗粒在肺泡上皮细胞中的细胞毒性阈值的测定基于体内外剂量模型。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-07 DOI: 10.1080/01480545.2026.2727999

Athena Rafieepour, Maryam Soleimani Alyar, Masoomeh Vahabi Shekarloo, Saber Moradi Hanifi, Mojtaba Yeganeh, Iraj Alimohammadi

{"title":"Determination of a cytotoxicity threshold for α-Fe2O3 nanoparticles based on an in vitro-in vivo dosimetry model in alveolar epithelial cells.","authors":"Athena Rafieepour, Maryam Soleimani Alyar, Masoomeh Vahabi Shekarloo, Saber Moradi Hanifi, Mojtaba Yeganeh, Iraj Alimohammadi","doi":"10.1080/01480545.2026.2727999","DOIUrl":"https://doi.org/10.1080/01480545.2026.2727999","url":null,"abstract":"This study aimed to extrapolate a cytotoxicity threshold in air using a combined in vitro-in vivo dosimetry model to assess the toxicity of α-Fe2O3 nanoparticles (NPs), innovatively applying this approach to NPs risk assessment. Cultured A549 cells treated with α-Fe2O3 NPs in various concentrations over 24-h and 72-h. Cell survival and mitochondrial membrane permeability were assessed using the MTT and MMP assay, respectively. The dose-response results served for estimating the Benchmark Dose (BMD) and BMDL using the EPA BMD software. BMDLs were extrapolated into equivalent air concentrations using the Combined Dosimetry model (CoDo). A significant loss in cell survival and a rise of mitochondrial membrane permeability, compared to the control group (P-value < 0.05), were observed after 24-h and 72-h, respectively. A time- and concentration-dependent pattern was observed in the toxicity of the A549 cell line. Extrapolated from a BMDL of 1.9 μg/mL, a 0.22 mg/m³ air concentration was found to correspond to the in vitro dose. The predicted cytotoxicity threshold falls below the current occupational exposure limits (OELs) for micro-scale particles. Although further in vivo and epidemiological studies are required to validate its relevance for occupational exposure settings, this modeling approach offers a valuable framework for preliminary risk assessment.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905400","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

N-nitrosodimethylamine increased glucose production by promoting hyperglycemia in hepatocyte via AMPK signaling pathway in vivo and in vitro. 在体内和体外实验中，n -亚硝基二甲胺通过AMPK信号通路促进肝细胞高血糖，从而增加葡萄糖的产生。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-01-03 DOI: 10.1080/01480545.2025.2609950

Wenxin Wang, Shuhua Xi, Yue Wang

{"title":"N-nitrosodimethylamine increased glucose production by promoting hyperglycemia in hepatocyte via AMPK signaling pathway in vivo and in vitro.","authors":"Wenxin Wang, Shuhua Xi, Yue Wang","doi":"10.1080/01480545.2025.2609950","DOIUrl":"10.1080/01480545.2025.2609950","url":null,"abstract":"N-nitrosodimethylamine (NDMA), as a disinfection by-product of drinking water, has been detected in various water. Epidemiological investigations have found that exposure to NDMA can exacerbate the development of diseases related to insulin resistance. In this study, male C57BL/6 mice were exposed to 0.5 and 12.5 mg/L NDMA by drinking water for 12 weeks. The mice in 12.5 mg/L NDMA group appeared fasting blood glucose elevation, and glucose tolerance and insulin sensitivity decreased. NDMA exposure enhanced hepatic gluconeogenesis and suppressed glycolysis of mice, but not affecting glycogen synthesis. In addition, NDMA exposure inhibited the phosphorylation of AMPK and FoxO1 as well as GLUT2 protein expression, and increased PGC-1α protein levels. GLUT2 protein decreasing could reduce glucose uptake of hepatocyte and enhance blood glucose concentration. Dephosphorylated FoxO1 might translocate to the nucleus, binding promoters of gluconeogenesis key enzymes PEPCK and G6Pase to upregulate their expression and promote gluconeogenesis. PGC-1α could also stimulate the expression of PEPCK and G6Pase. Furthermore, human normal liver cells (MIHA) were treated with NDMA for 24 hours. AMPK as a central energy sensor, regulates hepatic glucose production, uptake, and the process of glycolmetabolism. Therefore, AMPK agonist AICAR was used to explore the mechanism of NDMA causing hyperglycemia. AICAR reversed p-FoxO1, PGC-1α, GLUT2, PEPCK and G6Pase proteins expression and improved the glycolysis and glucose uptake capacity in NDMA treated MIHA cells. In conclusion, NDMA in drinking water led to fasting blood glucose enhancing, impairment of glucose tolerance and insulin sensitivity, increasing hepatic gluconeogenesis via AMPK signaling.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1049-1060"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892246","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

Cardioprotective effect of apigenin and carvedilol against isoproterenol-induced myocardial infarction in rats. 芹菜素和卡维地洛对异丙肾上腺素所致大鼠心肌梗死的保护作用。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-10-16 DOI: 10.1080/01480545.2025.2565350

Rehnuma Siddiquee, Tarique Mahmood, Vaseem Ahamad Ansari, Farogh Ahsan, Shahzadi Bano, Sana Ahmad, Mohd Masih Uzzaman Khan

{"title":"Cardioprotective effect of apigenin and carvedilol against isoproterenol-induced myocardial infarction in rats.","authors":"Rehnuma Siddiquee, Tarique Mahmood, Vaseem Ahamad Ansari, Farogh Ahsan, Shahzadi Bano, Sana Ahmad, Mohd Masih Uzzaman Khan","doi":"10.1080/01480545.2025.2565350","DOIUrl":"10.1080/01480545.2025.2565350","url":null,"abstract":"Myocardial infarction remains one of the leading causes of mortality and morbidity globally. While apigenin (AP), a trihydroxyflavone, and carvedilol, a beta blocker, have both been utilized in the treatment of cardiovascular diseases. There is a notable lack of comprehensive research or limited data regarding their combined cardioprotective activity. This gap emphasizes the need for further investigation into the potential synergistic effects of AP and carvedilol in the context of myocardial infarction. This study aims to evaluate the cardioprotective effect of AP and carvedilol in isoproterenol-induced myocardial infarction in rats. Male Sprague-Dawley rats were used and divided into five groups (n = 6). Isoproterenol (85 mg/kg/s.c.) was administered to induce myocardial infarction. AP (50 mg/kg/day/p.o) and carvedilol (5 mg/kg/day/p.o) were administered to rats for 14 days, along with Isoproterenol on the 15th and 16th days. Various parameters were estimated, including biochemical markers, cardiac markers, oxidative stress markers, antioxidants, and lipid profiles, to observe the effects of flavonoids and drugs. Administration of Isoproterenol showed changes in physical parameters, significantly elevated levels of serum biochemical markers, cardiac markers, oxidative stress markers, lipid profile, and decreased antioxidant enzymes. Treatment with AP and carvedilol diminished these changes very significantly. Histopathological examination of heart tissue in isoproterenol-induced rats showed necrotic lesions, which were reduced by the treatment with test drugs alone and in combination. Our study demonstrated that AP alone and in combination with carvedilol showed cardioprotective activity over isoproterenol-induced myocardial infarction in rats. Further investigations are needed to explore the underlying mechanism.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1087-1103"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298906","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 and subacute toxicity evaluation of a polyherbal blend in rats. 复方中草药对大鼠急性和亚急性毒性评价。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-01-11 DOI: 10.1080/01480545.2026.2612974

Prajakta H Murudkar, Akshay M Baheti, Anil T Pawar

{"title":"Acute and subacute toxicity evaluation of a polyherbal blend in rats.","authors":"Prajakta H Murudkar, Akshay M Baheti, Anil T Pawar","doi":"10.1080/01480545.2026.2612974","DOIUrl":"10.1080/01480545.2026.2612974","url":null,"abstract":"Many people often assume the safety of herbs and use them in the form of polyherbal blends to treat various health conditions. The present study aimed to evaluate the acute and subacute oral toxicity profile of a polyherbal blend in Wistar rats. The polyherbal blend was prepared to contain Terminalia chebula Retz., Terminalia bellirica (Gaertn.) Roxb., Phyllanthus emblica L., Curcuma longa L., Tribulus terrestris L., Pterocarpus marsupium Roxb., Tinospora cordifolia (Willd.) Miers, and Cinnamomum verum J. Presl. An acute oral toxicity study of a prepared polyherbal blend was conducted as per OECD guideline 423 and the subacute toxicity study was performed as per OECD 407 guidelines. There was no mortality and signs of toxicity at 2000 mg/kg single oral administration of polyherbal blend, indicating that the oral median lethal dose (LD50) is greater than 2000 mg/kg. The results of the subacute toxicity study indicated no significant changes in body weight, food and water consumption, hematological and biochemical parameters in rats treated with polyherbal blend at 250, 500 and 1000 mg/kg for 28 days when compared to their respective controls. Organ weights and histopathology showed no significant alterations in treated or satellite groups as compared to controls. It is concluded that the polyherbal blend is safe at a single dose of 2000 mg/kg and 28 days repeated dose of 1000 mg/kg by oral route in rats.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1236-1246"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951379","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

Salicylic acid attenuates paclitaxel-induced toxicity by modulating interleukin expression: an in vivo study. 水杨酸通过调节白细胞介素表达减轻紫杉醇诱导的毒性：一项体内研究。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-06-08 DOI: 10.1080/01480545.2025.2593476

Farah Al-Najar, Shahrzad Shahbazi, Somayeh Reiisi, Behnaz Saffar, Elham Moghtadaei Khorasgani

{"title":"Salicylic acid attenuates paclitaxel-induced toxicity by modulating interleukin expression: an in vivo study.","authors":"Farah Al-Najar, Shahrzad Shahbazi, Somayeh Reiisi, Behnaz Saffar, Elham Moghtadaei Khorasgani","doi":"10.1080/01480545.2025.2593476","DOIUrl":"10.1080/01480545.2025.2593476","url":null,"abstract":"Paclitaxel (PAX) is an effective chemotherapeutic agent for treating various cancers but is associated with side effects such as hepatotoxicity, neurotoxicity, and myelosuppression. To mitigate these toxicities, adjunct therapies like salicylic acid (SA), a plant-derived compound with anti-inflammatory, antioxidant, and cytoprotective properties, have been explored. This study investigates SA's potential to counteract PAX's cytotoxic effects, focusing on hepatic tissue. Thirty-five BALB/cJ mice were treated with PAX and SA, either individually or in combination (low and high doses), for 14 days. Post-treatment, biochemical and histological analyses were performed. ELISA assays measured serum levels of inflammatory markers IL-1β, IL-6, and TNF-α, while caspase-3/7 activity was evaluated to assess apoptosis. qPCR assessed gene expression related to apoptosis (CASP1, CASP3, Bcl-2). Results showed that PAX significantly increased serum levels of inflammatory markers, which were reduced by SA treatment. PAX also elevated caspase-3/7 activity, but co-treatment with SA suppressed this effect. Histological analysis revealed that low-dose SA alleviated PAX-induced necrosis and inflammation in the liver, kidney, and spleen. Moreover, PAX alone significantly upregulated CASP1 and CASP3 expression, while co-treatment with SA significantly downregulated these genes. These findings highlight the protective role of SA in reducing PAX-induced toxicity, particularly in hepatic tissues, suggesting that SA could be a potential adjunct therapy for minimizing chemotherapy-related side effects.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1213-1224"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204266","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

Linagliptin attenuates cisplatin-induced cardiotoxicity in rats via modulation of the SIRT1/AMPK/Nrf2 signaling pathway. 利格列汀通过调节SIRT1/AMPK/Nrf2信号通路减轻顺铂诱导的大鼠心脏毒性。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-08-11 DOI: 10.1080/01480545.2026.2711683

Mahdi H Alsugoor, Naif Al Suhaymi, Bassim M S A Mohamed, Mevidette Elmadani, Alyaa Farouk Hessin, Aya A Shokry, Sherif M Afifi, Reda Ms Korany, Gihan F Asaad, Hany M Fayed

{"title":"Linagliptin attenuates cisplatin-induced cardiotoxicity in rats via modulation of the SIRT1/AMPK/Nrf2 signaling pathway.","authors":"Mahdi H Alsugoor, Naif Al Suhaymi, Bassim M S A Mohamed, Mevidette Elmadani, Alyaa Farouk Hessin, Aya A Shokry, Sherif M Afifi, Reda Ms Korany, Gihan F Asaad, Hany M Fayed","doi":"10.1080/01480545.2026.2711683","DOIUrl":"10.1080/01480545.2026.2711683","url":null,"abstract":"Cisplatin (CP), an effective chemotherapeutic agent, is known to cause cardiotoxicity, limiting its clinical application. This study aimed to investigate the potential cardioprotective effects of linagliptin (LG) against cisplatin-induced cardiac injury and to elucidate its underlying mechanisms. There were four groups of male Wistar rats: control, cisplatin (CP, 8 mg/kg, IP), and two groups with LG treatment (5 mg/kg and 10 mg/kg, orally) and CP. CP significantly increased cardiac injury markers (CK, CK-MB, TNNC1) and oxidative stress (decreased SOD and GSH, increased MDA) compared to controls (p < 0.05). It also elevated inflammatory cytokines (TNF-α, IL-6) and disrupted mitochondrial function (altered ATP level and NADP/NADPH ratios). Furthermore, CP decreased the expression of SIRT1 and Nrf2 and the level of p-AMPK. LG treatment dose-dependently attenuated these changes, with the 10 mg/kg dose showing greater efficacy. Histopathological examination and immunohistochemistry confirmed these biochemical findings, showing improved cardiac structure and increased expression of SIRT1 and Nrf2 with LG treatment. Linagliptin demonstrates potent cardioprotective effects against cisplatin-induced toxicity, primarily through modulation of the SIRT1/AMPK/Nrf2 signaling pathway, thereby resulting in reduced oxidative stress and inflammation. These findings suggest that linagliptin may serve as a potential adjuvant therapy to mitigate cisplatin-induced cardiotoxicity.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1125-1139"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705853","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 effects of cirsimaritin against CCl₄-induced oxidative stress, inflammation, and apoptosis in rats. 茜草素对ccl4诱导的大鼠氧化应激、炎症和细胞凋亡的保护作用

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-11-12 DOI: 10.1080/01480545.2025.2579542

Yousra Bseiso, Badriyah S Alotaibi, Alaa A A Aljabali, Omar Gammoh, Muna Oqal, Esam Qnais, Abdelrahim Alqudah

{"title":"Hepatoprotective effects of cirsimaritin against CCl4-induced oxidative stress, inflammation, and apoptosis in rats.","authors":"Yousra Bseiso, Badriyah S Alotaibi, Alaa A A Aljabali, Omar Gammoh, Muna Oqal, Esam Qnais, Abdelrahim Alqudah","doi":"10.1080/01480545.2025.2579542","DOIUrl":"10.1080/01480545.2025.2579542","url":null,"abstract":"Background: Carbon tetrachloride (CCl4) induces hepatotoxicity through oxidative stress, inflammation, and apoptosis. Cirsimaritin, a natural flavonoid with antioxidant and anti-inflammatory activity, has not been extensively investigated for hepatoprotection.Methods: Male Wistar rats were allocated into four groups (n = 6): control, cirsimaritin-only (80 mg/kg/day), CCl4-only (1 mL/kg of 1:1 CCl4: olive oil, i.p., twice weekly), and cirsimaritin + CCl4. After four weeks, serum liver function markers, oxidative stress indices, cytokines, apoptotic markers, histology, and hepatic expression of Nrf2, HO-1, and NF-κB p65 were assessed.Results: CCl4 significantly elevated ALT, AST, ALP, bilirubin, MDA, TNF-α, IL-6, caspase-3, and caspase-9, while reducing albumin, total protein, SOD, CAT, GPx, IL-4, and IL-10 (p < 0.05-0.001). Cirsimaritin co-treatment reversed these alterations by normalizing liver enzymes, restoring antioxidant activity, lowering lipid peroxidation and pro-inflammatory cytokines, elevating anti-inflammatory cytokines, and attenuating apoptosis. Histology confirmed preservation of hepatic architecture. qPCR analysis showed that CCl4 downregulated Nrf2/HO-1 and upregulated NF-κB p65, whereas cirsimaritin significantly counteracted these molecular changes.Conclusion: Cirsimaritin protects against CCl4-induced hepatotoxicity by enhancing antioxidant defenses, correcting cytokine imbalance, and inhibiting apoptosis, at least partly via activation of Nrf2/HO-1 and suppression of NF-κB signaling. These findings highlight cirsimaritin as a promising natural hepatoprotective candidate.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1038-1048"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494961","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 and subacute oral toxicity of acetylated Ligubtrum lucidum Ait. polysaccharide in male mice. 乙酰化灵芝的急性和亚急性口服毒性。雄性小鼠中的多糖。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-11-13 DOI: 10.1080/01480545.2025.2574390

Yanli Xi, Mingyang Huo, Rixin Zang, Weijie Du, Haonan Jiang, Hongxia Gao, Meiyao Song, Kunjie Gong, Na Xu

{"title":"Acute and subacute oral toxicity of acetylated Ligubtrum lucidum Ait. polysaccharide in male mice.","authors":"Yanli Xi, Mingyang Huo, Rixin Zang, Weijie Du, Haonan Jiang, Hongxia Gao, Meiyao Song, Kunjie Gong, Na Xu","doi":"10.1080/01480545.2025.2574390","DOIUrl":"10.1080/01480545.2025.2574390","url":null,"abstract":"Ligustrum lucidum polysaccharide (FLL-P) is a class of important bioactive macromolecules extracted from the traditional Chinese medicinal herb wine-steamed Ligustrum lucidum Ait. As one of the key active components responsible for the pharmacological effects of this herb, its modern pharmacological value has garnered widespread attention. Research has demonstrated that FLL-P exhibits diverse and significant biological activities, with potential applications that far exceed the traditional scope of Chinese medicine. In recent years, chemical modification has been recognized as an effective strategy for enhancing the biological activity of polysaccharides. Consequently, structural modification of FLL-P is anticipated to further augment its activity and broaden its application prospects. However, current research on the chemical modification of FLL-P remains inadequate, particularly concerning the safety evaluation of modified products, which is still extremely limited. This research comprehensively explores the acetylation modifications of FLL-P, encompassing detailed characterization and toxicity assessments. The optimal product, identified as acetylated FLL-P 12.5 (FLL-PA12.5), was established through analyses of the degree of substitution (DS), FT-IR, and NMR. Toxicity tests, both acute and subacute, were conducted on male mice. The findings indicated that FLL-PA12.5 had a median lethal dose (LD50) exceeding 2000 mg/kg and a no-observed adverse effect level (NOAEL) of 250 mg/kg. Administration of FLL-PA12.5 at doses between 250 and 2000 mg/kg resulted in alterations in various oxidative stress-related parameters in different organs of the mice. These findings indicate that FLL-PA12.5 is a promising therapeutic candidate with an acceptable safety profile, warranting further pharmacological exploration.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1140-1153"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502868","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 glycine against diclofenac-induced toxicity in isolated rat hepatocytes. 甘氨酸对离体大鼠肝细胞双氯芬酸毒性的保护作用。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2025-10-10 DOI: 10.1080/01480545.2025.2564433

Mostafa G Elkot, Hisham A Nematalla, Ihab T Abdel-Raheem, Asser I Ghoneim

{"title":"Protective effects of glycine against diclofenac-induced toxicity in isolated rat hepatocytes.","authors":"Mostafa G Elkot, Hisham A Nematalla, Ihab T Abdel-Raheem, Asser I Ghoneim","doi":"10.1080/01480545.2025.2564433","DOIUrl":"10.1080/01480545.2025.2564433","url":null,"abstract":"Diclofenac (DIC) is a common cyclo-oxygenase inhibitor that has been linked to liver toxicity. Alternatively, glycine (GLY) has several beneficial actions, including direct cytoprotective, anti-inflammatory, anti-apoptotic, and antioxidant effects. Hence, this study investigated the ability of GLY to protect isolated rat hepatocytes against DIC-induced injury. Hepatocytes were isolated using a modified collagenase-based rat liver perfusion and digestion method. Assessment was conducted on trypan blue (TB) uptake, as well as, reduced glutathione (GSH), lipid peroxidation (LPO), nitric oxide (NO), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α) levels. Caspase-3 activity was also measured. Pre-incubation of hepatocytes with GLY (40 mM) for 30 minutes prior to treatment with DIC (200 µM) significantly mitigated hepatocytotoxicity. Additionally, the DIC-depleted GSH level was restored following GLY pretreatment. Moreover, levels of LPO, NO, NF-κB, TNF-α, and caspase-3 activity were normalized and diminished relative to the DIC-intoxicated group. Therefore, GLY prevented DIC-induced hepatocyte toxicity, at least partly, by its cytoprotective, antioxidative, anti-inflammatory, and anti-apoptotic properties. Further research regarding the clinical pharmacologic and toxicologic effects of administering GLY to patients treated with high-dose DIC is thus recommended.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1021-1031"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273923","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

Hydroxytyrosol suppressed the nephrotoxicity of cisplatin while supporting its therapeutic potential in a rat model of hepatocellular carcinoma. 羟基酪醇抑制顺铂的肾毒性，同时支持其在肝细胞癌大鼠模型中的治疗潜力。

IF 2.2 4区医学

Drug and Chemical Toxicology Pub Date : 2026-09-01 Epub Date: 2026-05-13 DOI: 10.1080/01480545.2026.2670721

Tuba Yalçın, Sercan Kaya, Can Ali Ağca, Akın Yiğin, Fatih Demir

{"title":"Hydroxytyrosol suppressed the nephrotoxicity of cisplatin while supporting its therapeutic potential in a rat model of hepatocellular carcinoma.","authors":"Tuba Yalçın, Sercan Kaya, Can Ali Ağca, Akın Yiğin, Fatih Demir","doi":"10.1080/01480545.2026.2670721","DOIUrl":"10.1080/01480545.2026.2670721","url":null,"abstract":"Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. The most important side effect of the chemotherapeutic agent Cisplatin (CIS) is nephrotoxicity. This study aimed to determine how Hydroxytyrosol (HxT), a potent antioxidant, affects the chemotherapeutic effect of CIS against Diethylnitrosamine (DENA)-induced HCC in liver tissue and its effectiveness on the damage caused by CIS in kidney tissues. In the experimental design, 56 male rats were divided into 8 groups (n = 7) for an 8-week experimental period. The rats were randomly assigned to one of the following groups: Control, HCC, HCC+HxT, HCC+CIS, CIS, CIS+HxT, HCC+CIS+HxT, and HxT, in equal numbers (n = 7). The effects of HxT in the HCC and/or CIS groups were examined using biochemical, histopathological, immunohistochemical, real-time PCR, and Western blot techniques. The study found increased liver and kidney function tests, histopathological changes, endoplasmic reticulum stress (ERS) markers, and inflammatory markers in the HCC and/or CIS groups compared to the control group. Furthermore, decreased levels of Phoenixin-14 (PNX-14), an endogenous polypeptide, were observed in the HCC and/or CIS groups compared to the control group. Significantly improved changes resulting from HCC and/or CIS were observed in the HxT-treated groups. Furthermore, cell culture analyses revealed that HxT exhibited cytotoxic effects against the HCC cell line. Conclusively, HxT supplementation demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effects against CIS-induced nephrotoxicity. However, the combination of CIS and HxT may have a more effective anticancer effect against HCC rather than using them separately.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1061-1086"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927564","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