Drug and Chemical Toxicology最新文献

{"title":"Low concentrations of complex mixtures of pesticides and metabolites are toxic to common Carp brain cells (<i>Cyprinus carpio carpio</i>).","authors":"Aliciane de Almeida Roque, Jessica Zablocki da Luz, Francisco Filipak Neto, Iris Barjhoux, Damien Rioult, Ciro Alberto de Oliveira Ribeiro","doi":"10.1080/01480545.2024.2397432","DOIUrl":"10.1080/01480545.2024.2397432","url":null,"abstract":"<p><p>Pesticide use increases annually, and Brazil is the world's largest consumer. However, unlike the European Union (EU), there is no established limit value for pesticide mixtures in drinking water, and therefore the concentration of pesticides can reach 3354 times the EU limit. Thus, determining the risk of exposure to pesticide mixtures and their main metabolites is challenging and requires the use of alternative methods. In the present study, the Common Carp Brain (CCB) cell line was used to evaluate the in vitro toxicity of relevant pesticide mixtures (glyphosate, 2,4-D, atrazine, and mancozeb) and their main metabolites after 72 h of exposure. The tested concentrations were based on the Acceptable Daily Intake (ADI) defined by Brazilian legislation. The results showed that cells exposed to lower concentrations of the pesticide mixtures and the pesticide + metabolite mixtures were affected by a decrease in cell confluence, resazurin metabolism, and wound healing capacity. The IBR index showed that lower concentrations had more severe effects, suggesting the absence of safe concentrations of these pesticide and metabolite mixtures for the CCB cell line within the tested concentration range. These findings raise concerns about the effects of exposure to these substances on animal and human health.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"314-324"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105419","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}

{"title":"Metabolic syndrome prevalence in Mexican individuals exposed to polycyclic aromatic hydrocarbons and their association with an increased risk of cardiovascular events.","authors":"Iván Nelinho Pérez-Maldonado, Carlos Gabriel De la Trinidad-Chacón, Amairani Lizbeth Pérez-López, Anette Aylin Pérez-López, José Antonio Varela-Silva","doi":"10.1080/01480545.2024.2444367","DOIUrl":"10.1080/01480545.2024.2444367","url":null,"abstract":"<p><p>Polycyclic aromatic hydrocarbons (PAHs) are an organic chemical family produced during incomplete combustion of organic materials. Besides, PAHs are associated with different detrimental health effects. Therefore, this research was aimed to assess the association between PAHs exposure, metabolic syndrome (MetS) prevalence, and cardiovascular risk in a Mexican population. Urinary 1-hydroxypyrene (1-OHP) was the exposure biomarker quantified. MetS prevalence was defined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the International Diabetes Federation (IDF) criteria. Also, we used the atherogenic index of plasma (AIP) as a cardiovascular risk biomarker. The mean urinary 1-OHP level quantified was 2.50 ± 1.25 µmol/mol creatinine. The MetS prevalence found was 35% (<i>n</i> = 222) and 31% (<i>n</i> = 197) using NCEP ATP III and IDF criteria, respectively. The mean AIP value was 0.32 ± 0.15. Furthermore, the data analysis showed robust associations between PAH exposure (urinary 1-OHP concentrations), MetS prevalence, and cardiovascular risk (AIP). The real significance of the findings in this study needs to be clarified completely, as MetS and cardiovascular diseases represent a critical challenge in contaminated zones of developing countries such as Mexico.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"344-353"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902350","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}

{"title":"Analysis of key targets for 5-hydroxymethyl-2-furfural-induced lung cancer based on network toxicology, network informatics, and <i>in vitro</i> experiments.","authors":"Tianchi Zhuang, Chang Gao, Wei Zeng, Wenwu Zhao, Hairong Yu, Shen Chen, Jiemiao Shen, Minghui Ji","doi":"10.1080/01480545.2024.2384442","DOIUrl":"10.1080/01480545.2024.2384442","url":null,"abstract":"<p><p>5-hydroxymethyl-2-furfural (5-HMF) is a by-product of Maillard reaction and widely exists in food and environment, which may lead to lung cancer. However, the relevant mechanism is unknown. This study aims to predict the key targets of 5-HMF-induced lung cancer through network toxicology, analyze the relationship between the key targets and lung cancer through network informatics, and further validate them through <i>in vitro</i> experiments. By using ChEMBL, STITCH, GeneCards, and OMIM databases, 51 toxic targets were identified. GO and KEGG enrichment analyses indicated a strong correlation between toxic targets and lung cancer. Through protein-protein interaction (PPI) analysis, MAPK3, MAPK1, and SRC were identified as key targets implicated in 5-HMF-induced lung cancer. The HPA database showed high expression of these three key targets in lung cancer tissues. Kaplan-Meier database demonstrated that the higher expression of these key targets in lung cancer patients was associated with a poorer prognosis. The TIMER database revealed that the high expression of these key targets had a significant impact on the level of immune cell infiltration in lung cancer, particularly impacting CD4+ T cells and macrophages. Finaly, in <i>In vitro</i> experiments demonstrated that prolonged exposure to 5-HMF induced malignant transformation of BEAS-2B cells and the upregulation of key targets. The findings suggest that 5-HMF is a contributing factor in the development of lung cancer, with MAPK3, MAPK1, and SRC potentially playing crucial roles in this process.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"451-461"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787555","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}

{"title":"Computational and experimental study of terpolymers: spectroscopic, thermal, thermochemical, molecular property, and <i>in silico</i> toxicity analysis.","authors":"Nevin Çankaya, Mehmet Hanifi Kebiroglu, Cengiz Soykan","doi":"10.1080/01480545.2025.2468924","DOIUrl":"https://doi.org/10.1080/01480545.2025.2468924","url":null,"abstract":"<p><p>In this study, a comprehensive analysis of the CMA2OEM-co-DVB-co-AMPS (2-(bis(cyanomethyl)amino)-2-oxoethyl methacrylate-co-divinylbenzene-co-2-acrylamido-2-methyl-1-propanesulfonic acid) and CMA2OEM-co-DVB-co-VIM (2-(bis(cyanomethyl)amino)-2-oxoethyl methacrylate-co-divinylbenzene-co-vinylimidazole) terpolymers was conducted. The structural and chemical properties of the terpolymers were examined using Fourier transform infrared (FT-IR) spectroscopy, frontier molecular orbital analysis, molecular electrostatic potential (MEP) maps, ¹H, and ¹³C NMR spectroscopy, thermochemistry surface maps (TCSM), toxicity assessments, physical properties, electron localization function (ELF), and total electrostatic potential (ESP) analyses. <i>In silico</i> toxicity analyses, a quantitative structure-activity relationship (QSAR) model was used for Toxicity Estimation Software Tool (TEST) and ProTox 3.0, a web-based virtual toxicity laboratory, was used for oral toxicity prediction. Toxicity estimates using TEST showed that both terpolymers exhibited low toxicity profiles. Oral toxicity prediction emphasizes that CMA2OEM-co-DVB-co-VIM may pose a greater risk compared to CMA2OEM-co-DVB-co-AMPS. In addition, experimental thermal characterization of these terpolymers was also performed. These comprehensive analyses have provided significant insights into the potential applications and functional properties of the terpolymers.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527933","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}

{"title":"Antioxidant capacity, acute and sub-acute oral toxicity, and <i>in vivo</i> anti-inflammatory effects of <i>Tetradenia riparia</i> hydroalcoholic extract.","authors":"Martin Ndayambaje, Thierry Habyarimana, Hicham Wahnou, Aimable Nsanzurwimo, Oumaima Chgari, Pacifique Ndishimye, Asmaa Mezty, Mernissi Farida, Mehdi Karkouri, Younes Zaid, Abdallah Naya, Mounia Oudghiri","doi":"10.1080/01480545.2025.2468932","DOIUrl":"https://doi.org/10.1080/01480545.2025.2468932","url":null,"abstract":"<p><p><i>Tetradenia riparia (T. riparia</i>) is a medicinal plant native to sub-Saharan Africa, traditionally used but has limited <i>in vivo</i> scientific validation. This study evaluated its antioxidant, toxicity, and anti-inflammatory effects using <i>in vivo</i> toxicity tests, paw edema, air pouch models, and vascular permeability assessment. Additionally, qualitative phytochemical analysis and quantitative measurements of total polyphenolic and flavonoid content were conducted. <i>In vitro</i> assays revealed significant concentrations of polyphenolic and flavonoid compounds, demonstrating notable radical scavenging activities in DPPH, phosphomolybdate, and FRAP assays. <i>In vivo</i> studies demonstrated that <i>T. riparia</i> extract showed no indications of acute or sub-acute oral toxicity, even when administered at the highest tested dosage of 5000 mg/kg body weight (LD50 > 5000 mg/kg). Toxicity assessments confirmed its safety, showing no fatalities, significant organ damage as evidenced by histopathological analysis, or substantial adverse effects on most hematological and biochemical parameters. The hydroalcoholic extract of <i>T. riparia</i> demonstrated a notable anti-inflammatory effect that increased with dosage. The inhibition percentage of paw edema by the extract was high at 3 hours, reaching 39.13 ± 8.78%. Nitric oxide (NO) inhibition at doses of 0.5 g/kg and 1 g/kg was recorded as 36.09 ± 2.13% and 49.96 ± 5.41%, respectively. Regarding vascular permeability, <i>T. riparia</i> extract significantly reduced dye leakage (p < 0.05 and p < 0.001), with inhibition percentages of 61.57% and 75.25% at doses of 0.5 g/kg and 1 g/kg, respectively. These findings highlight its promising potential as a treatment for inflammatory disorders. In conclusion, phytochemical analysis identified compounds, which are believed to be responsible for the pharmacological effects observed. Further studies are needed to investigate the chronic consumption of hydroalcoholic extract for long-term isolate bioactive compounds, understand their mechanisms, ensure comprehensive safety profiles for potential drug development, and elucidate their anti-inflammatory mechanism.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482492","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}

{"title":"Damage to the sarcoplasmic reticulum by venom of the Mexican black-tailed rattlesnake (<i>Crotalus molossus nigrescens</i>): inhibition of the Ca²⁺-ATPase and membrane lipid disruption.","authors":"Luis Fernando Plenge-Tellechea, David Meléndez-Martínez, César Emmanuel Rivas-Valles, Ana Gatica-Colima, Martha Sandra Cruz-Pérez, Jorge A Sierra-Fonseca","doi":"10.1080/01480545.2025.2463369","DOIUrl":"https://doi.org/10.1080/01480545.2025.2463369","url":null,"abstract":"<p><p>Snakebite envenomation is a public health problem in many areas in the world and is a significant cause of disability and death. Crotalid venoms consist of a cocktail of peptides and enzymes that can cause myonecrotoxic lesions, which are associated with irreversible loss of muscle tissue. The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) is a transmembrane protein with a critical role in maintaining cellular Ca²⁺ homeostasis, which is central in facilitating skeletal and cardiac muscle contraction/relaxation. Crotalid venom-induced myotoxicity has been linked to alterations in the intracellular levels of Ca²⁺. However, the specific mechanisms, including SERCA's involvement, are poorly understood. Thus, we investigated the <i>in vitro</i> toxic effect of crotalid venom on the enzymatic activity of SERCA, using venom of the Mexican black-tailed rattlesnake, <i>Crotalus molossus nigrescens</i>, (v<i>Cmn</i>), and SERCA-enriched sarcoplasmic reticulum (SR) microsomes from rabbit skeletal muscle as experimental models. Enzymatic assays revealed significant v<i>Cmn</i>-induced decreases in SERCA activity in a time- and dose-dependent manner. Thin layer chromatography and phospholipid hydrolysis measurements showed significant SR membrane damage. The results suggest that v<i>Cmn</i> affects SERCA functionality and compromises the integrity of the SR membrane, both of which are critical for skeletal muscle function and could thus be key mediators of v<i>Cmn</i>-induced myotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381753","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}

{"title":"Mitigative and neuroprotective effects of <i>Lavandula angustifolia</i> essential oil on serotonin syndrome-induced neurotoxicity in male albino rats.","authors":"Manal A Babaker, Naema Ibolgasm Alazabi, Shimaa A Haredy, Ayman Mohamed Algohary, Mai M Anwar, Einas M Yousef, Omar A Ahmed-Farid","doi":"10.1080/01480545.2025.2458618","DOIUrl":"https://doi.org/10.1080/01480545.2025.2458618","url":null,"abstract":"<p><p>The term serotonin syndrome (SS) is a potentially life-threatening devastating condition triggered by the excessive accumulation of serotonin, often due to an overdose or the concurrent use of multiple serotonergic drugs. <i>Lavandula angustifolia</i> (lavender), a known plant from the Lamiaceae family, is very rich in essential oils, minerals, and tannins. This study aimed to elucidate the detrimental effects of SS on the brain and to evaluate the neuroprotective potential of <i>L. angustifolia</i> essential oil. Male rats were randomly divided into the following groups: control (Group 1); <i>L. angustifolia</i>-treated (Group 2); ondansetron-treated high-dose (Group 3); sertraline-treated high-dose (Group 4); low-dose ondansetron + sertraline-treated (Group 5); high-dose ondansetron + sertraline-treated (Group 6); low-dose ondansetron + sertraline + <i>L. angustifolia</i>-treated (Group 7); and high-dose ondansetron + sertraline + <i>L. angustifolia</i>-treated (Group 8). Neurotransmitter levels, dopamine metabolites, and expressed cytokines were quantified. Additionally, histological assessment of the hippocampus was performed. The results revealed significant disruptions in neurotransmitter and amino acid levels within the hippocampus across the treated groups. Notably, the high-dose ondansetron + sertraline group presented pronounced increases in serotonin, 5-HIAA, and proinflammatory cytokines, resulting in neurotoxicity and pronounced alterations in the hippocampus. Conversely, treatment with <i>L. angustifolia</i> significantly attenuated these neurotoxic effects. The findings suggest that <i>L. angustifolia</i> confers neuroprotection against the deleterious effects of SS, particularly by counteracting the neurotoxic impact of combined serotonin 5-HT3 receptor antagonists and serotonin reuptake inhibitors within the hippocampus. These findings highlight the potential of <i>L. angustifolia</i> as a natural therapeutic agent for mitigating SS-induced neurotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-19"},"PeriodicalIF":2.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078911","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}

{"title":"Effect of adenosine triphosphate on methylphenidate-induced oxidative and inflammatory kidney damage in rats.","authors":"Bahtinur Yeter, Zeynep Suleyman, Seval Bulut, Betul Cicek, Taha Abdulkadir Coban, Ozlem Demir, Halis Suleyman","doi":"10.1080/01480545.2025.2457386","DOIUrl":"https://doi.org/10.1080/01480545.2025.2457386","url":null,"abstract":"<p><p>The purpose of this trial was to assess the effects of methylphenidate on the kidney tissues and to investigate the protective effect of adenosine triphosphate (ATP) against possible methylphenidate nephrotoxicity in rats. The rats were separated into; healthy control (HG), methylphenidate (MPHG), ATP (ATPG), and ATP+ methylphenidate (AMPG). The ATPG and AMPG groups were administered ATP 4 mg/kg bw/d, and the HG and MPHG groups received distilled water intraperitoneally. One hour from, ATP and distilled water administration, methylphenidate 10 mg/kg bw/d was applied <i>via</i> oral gavage to the AMPG and MPHG groups once daily for 30 d (1 × 1). Animals were euthanized after 30 d and tissues were collected. The levels of certain oxidant/antioxidant parameters, pro-inflammatory cytokines, and Blood urea nitrogen (BUN) and creatinine levels were measured. Kidneys were also examined histopathologically. ATP inhibited the increase in oxidant and decrease antioxidant levels induced by methylphenidate. The amounts of pro-inflammatory cytokines were increased in methylphenidate-treated kidney tissue compared with the HG and AMPG groups. However, ATP increased oxidative damage markers and cytokines levels close to the healthy group. Serum BUN and creatinine levels increased with methylphenidate but ATP prevented BUN and creatinine from rising in the ATPG and MPHG groups. ATP also reduced the histopathological damage increased by methylphenidate. The potential efficacy of ATP in treating kidney damage induced by methylphenidate use.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064437","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}

{"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 <i>Oroxylum indicum</i> 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":"https://doi.org/10.1080/01480545.2024.2449210","url":null,"abstract":"<p><p><i>Oroxylum indicum</i> 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 <i>O. indicum</i> 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.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","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}

{"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":"https://doi.org/10.1080/01480545.2025.2453590","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"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}