Drug and Chemical Toxicology最新文献

{"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}

{"title":"Novel chlorinated oxime K870 protects rats against paraoxon poisoning better than obidoxime.","authors":"Žana M Maksimović, Sonja T Marinković, Đorđe Đukanović, Nebojša Mandić-Kovačević, Snežana Uletilović, Mladen Duran, Kamil Kuča, Kamil Musilek, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković","doi":"10.1080/01480545.2025.2454279","DOIUrl":"https://doi.org/10.1080/01480545.2025.2454279","url":null,"abstract":"<p><p>The aim of this study was to determine the antidotal potential of the chlorinated oxime K870 compared to obidoxime, as a monotherapy and in combination with atropine, in paraoxon (POX)-poisoned rats. The treatment doses of oximes were chosen as 20% of their LD₅₀ values. The protective ratio (PR) of oxime K870 with atropine was significantly higher than that of obidoxime with atropine (68.8 and 125.0, respectively). In the biochemical part of the experiment POX subcutaneously (s.c.) (0.75% LD₅₀) was administered and followed by oxime K870 or obidoxime i.m. 1 min later. Acetylcholinesterase (AChE) activity was determined spectrophotometrically in cerebrum, cerebellum, brainstem, diaphragm, and erythrocytes. Carboxylesterase activity was determined in plasma and liver. Both oximes successfully reactivated AChE in brain (cerebrum, cerebellum, and brainstem), diaphragm and erythrocytes, but the oxime K870 performed better than obidoxime. Both oximes reactivated carboxylesterase, obidoxime better in plasma and oxime K870 better in liver. In conclusion, the oxime K870, when co-administered with atropine, is a more effective antidote than the obidoxime-atropine combination in POX-poisoned rats.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051970","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":"Protective effects of herbal compounds against cyclophosphamide-induced organ toxicity: a pathway-centered approach.","authors":"Prathap Srirangan, Evan Prince Sabina","doi":"10.1080/01480545.2025.2455442","DOIUrl":"https://doi.org/10.1080/01480545.2025.2455442","url":null,"abstract":"<p><p>Cyclophosphamide is a key component of numerous chemotherapeutic protocols, demonstrating broad-spectrum efficacy against various malignancies and non-cancerous conditions. This review examines CPM's metabolic pathways, therapeutic applications, and its resulting organ-specific toxicities. Despite its clinical benefits in treating nephrotic syndrome, encephalomyelitis, breast cancer, ovarian cancer, and other diseases, CPM is associated with significant adverse effects on the kidneys, liver, heart, lungs, and intestines. The discussion delves into the molecular mechanisms underlying these toxicities, highlighting dysregulation in key signaling pathways, including Nrf2, NF-κB, MAPK/ERK, and AKT. In addressing these challenges, recent studies have identified various herbal drugs and phytochemicals capable of mitigating CPM-induced toxicity. Notable compounds such as cinnamaldehyde, baicalin, quercetin, and curcumin have demonstrated protective effects. Integrating these herbal formulations with CPM therapy is proposed to enhance patient safety and treatment efficacy. This review underscores the influence of CPM on apoptosis and inflammation pathways, which lead to alterations in organ-specific biomarkers. Phytochemicals may exert protective effects by restoring disrupted signaling pathways and normalizing altered biomarkers. The compilation of phytochemicals presented in this review serves as a valuable resource for researchers exploring other herbal products with potential protective effects against CPM toxicity. A significant gap in the current literature is the lack of clinical trials evaluating phytochemicals that mitigate CPM toxicity in vivo. Rigorous clinical studies are necessary to establish the efficacy and safety of herbal formulations in cancer treatment. Such research will clarify the role of natural remedies in complementing conventional therapies, ultimately improving patient outcomes.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-43"},"PeriodicalIF":2.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028317","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":"Investigation of the effects of silymarin and vitamin C on kidney damage and aquaporin-2 downregulation in lithium-induced nephrogenic diabetes insipidus in rats.","authors":"Seda Yakut, Berrin Tarakçı Gençer, Mehmet Hanifi Yalçın, Süleyman Aydın, Hayati Yüksel","doi":"10.1080/01480545.2025.2450475","DOIUrl":"https://doi.org/10.1080/01480545.2025.2450475","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial toxicity of selected natural compounds: <i>in vitro</i> assessment and <i>in silico</i> molecular docking and dynamics simulation.","authors":"Ali Ergüç, Gökay Albayrak, Muhammed Tilahun Muhammed, Fuat Karakuş, Ege Arzuk","doi":"10.1080/01480545.2024.2412775","DOIUrl":"10.1080/01480545.2024.2412775","url":null,"abstract":"<p><p><i>Prangos uechtritzii</i> Boiss & Hausskn stands out for its rich bioactive constituents including prantschimgin (PRA), imperatorin (IMP), suberosin (SUB), adicardin (ADI), and oxypeucedanin hydrate (OPH) in the Apiaceae family. Although these molecules contribute to several biological activities, their mitochondrial toxicity were not illuminated in depth with the appropriate <i>in vitro</i> and <i>in silico</i> models. Cell viability studies investigated the cytotoxic activities of molecules in HepG2 cells by replacing glucose with galactose due to Warburg effects. Mitochondrial toxicity (mitotoxicity) parameters such as cellular adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) levels were assessed with cytotoxic concentrations of selected molecules. Molecular docking and dynamics studies were also conducted against mitochondrial electron transport chain (ETC) complexes (I-V) with selected compounds. <i>In vitro</i> results showed that PRA, SUB, and IMP reduced cell viability more in galactose media compared to high glucose media in a dose-dependent manner. PRA, IMP, and SUB decreased ATP levels and MMP, especially in the galactose medium. The <i>in silico</i> study revealed that PRA, IMP, and SUB might bind to complexes I-V at different levels. The docking study demonstrated that PRA had the highest binding potential with the complexes, higher than the standard ligands in some cases. The molecular dynamics (MD) simulation study showed that PRA formed stable complexes with complexes II, III, and IV. In addition, PRA was anticipated to remain inside the binding site of complex II most stably during the 230 ns simulation period. Our study suggests that PRA, IMP, and SUB exhibit mitotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"199-209"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol mitigates methotrexate-induced hepatic injury via SIRT-1/p53 signaling and mitochondrial pathways: reduces oxidative stress and inflammation.","authors":"Ilter Ilhan, Halil Asci, Ibrahim Aydın Candan, Mehtap Savran, Orhan Berk Imeci, Mehmet Abdulkadir Sevuk","doi":"10.1080/01480545.2024.2425994","DOIUrl":"10.1080/01480545.2024.2425994","url":null,"abstract":"<p><p>Methotrexate (MTX), a widely used chemotherapeutic agent, often induces hepatotoxicity, limiting its clinical utility. Cannabidiol (CBD), derived from hemp, possesses antioxidant, anti-inflammatory, and antiapoptotic properties. This study aims to investigate CBD's protective effects against MTX-induced liver injury and elucidate the underlying mechanisms. Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (20 mg/kg intraperitoneally [i.p.] once), MTX+CBD (20 mg/kg i.p. once + 5 mg/kg i.p. for seven days), and CBD (5 mg/kg, i.p. for seven days). Biochemical analyses of serum and liver tissues were performed to assess oxidative stress markers (total oxidant status, total antioxidant status, oxidative stress index), liver function tests (AST, ALT), and antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase). Histopathological and immunohistochemical examinations were conducted to evaluate liver tissue damage and TNF-α expression. Genetic analyses were performed to measure the expression levels of SIRT-1, p53, Bcl-2, and Bax genes using RT-qPCR. MTX administration increased oxidative stress markers, liver enzymes, TNF-α, p53, and Bax levels while decreasing antioxidant defenses and SIRT-1 expression. CBD administration reversed these alterations effectively. CBD mitigated MTX-induced hepatotoxicity by reducing oxidative stress, inflammation, and apoptosis. It activates antioxidant defenses via SIRT-1 upregulation, suppresses inflammation by reducing TNF-α, and prevents apoptosis by modulating p53, Bcl-2, and Bax gene expressions. These findings suggest CBD could be a promising therapeutic agent for chemotherapy-induced liver damage. Further research is warranted to explore additional pathways and broader molecular mechanisms.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"210-218"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neuroprotective effect of 1,25-dyhydroxyvitamin D₃ (calcitriol) and probiotics on the rotenone-induced neurotoxicity model in SH-SY5Y cells.","authors":"Fatma Hazan Gul, Nuh Mehmet Bozkurt, Nalan Hakime Nogay, Gokhan Unal","doi":"10.1080/01480545.2024.2429621","DOIUrl":"10.1080/01480545.2024.2429621","url":null,"abstract":"<p><p>This study aimed to investigate the neuroprotective role of probiotics and 1,25-dyhydroxyvitamin D₃ (calcitriol) against neurotoxicity on rotenone-induced human neuroblastoma cell line SH-SY5Y. Rotenone was administered to induce neurotoxic effects in SH-SY5Y cells. Calcitriol and probiotics were administered at different concentrations as pre- and post-treatment. The thiazolyl blue tetrazolium bromide (MTT) assay was performed to measure cell viability. Intracellular protein levels of antioxidant enzymes (protein tyrosine kinase (PTK), superoxide dismutase (SOD), glutathione peroxidase (GSH), glutathione reductase (GSR), and catalase (CAT)) were determined by the enzyme-linked immunosorbent assay (ELISA). Rotenone (150 nM) reduced (<i>p</i> < 0.001) cell viability compared to control cells. Single and combined pretreatments with probiotics (0.01 mg/ml, 0.05 mg/ml, and 0.1 mg/ml) and calcitriol (1.25 µM, 2.5 µM, and 5 µM) increased (<i>p</i> < 0.05) cell viability compared to rotenone group. In the pre- and post-treatment design, all treatment groups increased the SOD and GSH levels and decreased the GSR levels compared to rotenone. None of the pretreatments reversed the PTK levels (except probiotics: 0.01 mg/ml). Calcitriol (2.5 µM) increased the CAT levels in pretreatment design, and probiotics (0.05 mg/ml and 0.1 mg/ml) increased CAT levels in post-treatment design compared to rotenone group. Calcitriol and probiotics protect against rotenone-induced neurotoxicity in SH-SY5Y cells by decreasing reactive oxygen species (ROS) and increasing antioxidant enzyme parameters. These neuroprotective effects of calcitriol and probiotics against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for their potential clinical use in the treatment of Parkinson's disease (PD).</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"72-83"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}