Mohd Anas Saifi, Huma Khan, Mehjbeen Javed, Shahzad Ahmad, Zuber Khan, Anuradha Mangla, Garima Jindal, Suhel Parvez, Nidhi Agarwal, Sheikh Raisuddin
{"title":"Neuroprotective effects of gastrodin against bisphenol A induced-ADHD-like symptoms in rats.","authors":"Mohd Anas Saifi, Huma Khan, Mehjbeen Javed, Shahzad Ahmad, Zuber Khan, Anuradha Mangla, Garima Jindal, Suhel Parvez, Nidhi Agarwal, Sheikh Raisuddin","doi":"10.1080/01480545.2025.2473472","DOIUrl":"https://doi.org/10.1080/01480545.2025.2473472","url":null,"abstract":"<p><p>Gastrodin (GAS) is a potent pharmaceutical compound extracted from the dried roots of a Chinese medicinal herb, <i>Gastrodia elata</i> Blume. It has been used as a neuroprotective treatment for a range of neurological disorders. Bisphenol A (BPA) has been implicated in the induction of attention-deficit hyperactivity disorder (ADHD)-like symptoms. We investigated the neuroprotective effects of GAS against BPA-induced ADHD-like symptoms in the rat model. Weanling male Wistar rats treated with BPA (50 µg/kg b.w. × 30 days <i>per os</i>) on completion of treatment were subsequently treated with GAS at two doses (30 and 60 mg/kg b.w. i.p. × 7 days). After 24 hours of completion of the treatment regimen, neurobehavioral parameters such as open field test (OFT), novel object recognition (NOR), and elevated plus maze (EPM) test were evaluated. Lipid peroxidation, reduced glutathione (GSH), monoamine oxidase (MAO) activity, and dopamine (DA) levels were measured in the cerebral cortex (CC) and hippocampus (HC) regions of the brain. Additionally, to asses astrocyte activatio the expression of glial fibrillary acidic protein (GFAP) was analyzed by immunostaining. Results show that GAS treatment ameliorated locomotory activity (OFT), memory dysfunction (NOR), and anxious (EPM) behavioral alterations in BPA-treated animals. GAS treatment also reduced lipid peroxidation, enhanced GSH, MAO activity, and DA levels, and reduced GFAP-positive cells in the CC and HC regions thus providing experimental evidence for a neuroprotective role for GAS against BPA-induced ADHD-like symptoms. GAS demonstrated potential preventive effects against BPA-induced ADHD-like symptoms in rats which highlights its therapeutic value.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585065","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}
David Fisher, Omar Zabida, Sahar Abdul-Rasool, Chontrelle Willemse
{"title":"Cytotoxicity of methamphetamine exposure on Sertoli cells: a pilot study with implications for male infertility.","authors":"David Fisher, Omar Zabida, Sahar Abdul-Rasool, Chontrelle Willemse","doi":"10.1080/01480545.2025.2471383","DOIUrl":"https://doi.org/10.1080/01480545.2025.2471383","url":null,"abstract":"<p><p>Methamphetamine (Meth), a psychoactive drug, has been shown to reduce testicular weight and decrease sperm count, indicating its potential role in contributing to male infertility. We therefore assessed Meth's effects (0.1-100 μM) on TM4 Sertoli cell viability, toxicity, and proliferation (trypan blue exclusion assay), mitochondrial activity (MA) (XTT assay), while transepithelial electrical resistance (TEER) was used to examine monolayer permeability. The acute study (only 24-hour Meth exposure) mimics recreational users and the chronic study, the Meth addicts who require daily doses (24-96 hours). Acute Meth treatment had minimal impact on TM4 Sertoli cell viability and toxicity, while chronic exposure resulted in reduced cell viability and increased toxicity in a dose-related manner. Acute exposure suppressed cell division at 72 hours, while chronic exposure suppressed cell division at both 72 and 96 hours. Long-term suppression of MA was observed for both acute and chronic Meth exposure (20 µM and 100 µM). Both acute and chronic Meth exposure affected permeability across the blood-testis barrier (BTB), which persisted for up to 96 hours. Given the pivotal role of Sertoli cells in spermatogenesis, our findings provide a two-pronged mechanism for Meth-induced male infertility and indicate that short-term exposure may have long-term effects on the germinal epithelium.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540550","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":"Correction.","authors":"","doi":"10.1080/01480545.2025.2473759","DOIUrl":"https://doi.org/10.1080/01480545.2025.2473759","url":null,"abstract":"","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540549","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}
Mary Nancy Flora R, Chamundeeswari M, Selvaraj R, Palani S
{"title":"Toxicity optimization of green zinc oxide quantum dots in zebrafish using Box-Behnken design: a novel approach for safer nanoparticle synthesis.","authors":"Mary Nancy Flora R, Chamundeeswari M, Selvaraj R, Palani S","doi":"10.1080/01480545.2024.2417960","DOIUrl":"10.1080/01480545.2024.2417960","url":null,"abstract":"<p><p>Zinc oxide quantum dots, also known as ZnO QDs, are highly desirable due to their numerous favorable characteristics, such as their beneficial photoluminescence, solubility in water, along with sunlight absorption. They are well-suited for use in biomedical applications, drugs, and bioimaging. However, study on the <i>in-vivo</i> toxicology of these QDs is needed before they can be used in humans. Zebrafish (<i>Danio rerio</i>) are cheap, fast-growing, and similar to humans, which makes them ideal as in vivo model for studying the toxicity of nanomaterials. The toxicity investigations involving zinc oxide QDs (ZnO QDs) and zinc oxide bionanocomposite (ZnO BC) in zebrafish that were concentration-dependent are evaluated, and the Box-Behnken design (BBD) was utilized to optimize the results. To determine the proper dosage, a study on cell line as well as hemocompatibility was carried out prior to testing the toxic effects of ZnO QDs along with ZnO BC upon zebrafish. When administered at 2.5 μg/l of ZnO BC and 2 μg/l of ZnO QDs, neither ZnO BC nor ZnO QDs appeared to be toxic to embryos during hatching and development. The testing of larval behavior in visible light revealed a dose-dependent decrease in both the total diving distance as well as speed. Nevertheless, at ZnO BC and ZnO QDs levels >250 μg/l and >200 μg/l, respectively, notable effects were seen in zebrafish embryos. Hence, ZnO QDs and BC at low concentrations were notably nontoxic. In order to guarantee the safety of nanomaterials in bio applications, this research supports upcoming <i>in-vivo</i> imaging investigations on their harmful effects.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"367-380"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460508","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":"Untargeted metabolic profiling of high-dose methotrexate toxicity shows alteration in betaine metabolism.","authors":"Shahid Karim, Huda Alkreathy, Mohammad Imran Khan","doi":"10.1080/01480545.2024.2369587","DOIUrl":"10.1080/01480545.2024.2369587","url":null,"abstract":"<p><p>Cardiotoxicity is a well-established adverse effect of several drugs across multiple therapeutic indications. It is particularly prevalent following anticancer therapy. In order to evaluate the changes in cellular metabolism associated with methotrexate cardiotoxicity, we treated Wistar rats with a single high dose of methotrexate (HDMTX), and after five days, the animals were sacrificed. We then analyzed the cardiotoxicity parameters in serum like Cardiac enzymes(CK-MB, Troponin T, ALP), Inflammatory markers (TNF-<i>α</i> and IL-6), oxidative stress markers (NO, NOX-2), histopathology and cardiac tissue with the goal of identifying a metabolic signature of cardiotoxicity using discovery-based metabolomics. The biochemical parameters for cardiac enzymes, oxidative stress and inflammatory markers showed a significant increase in all three categories in rats treated with HDMTX. These findings were mirrored in the histopathological analysis confirming cardiotoxicity due to HDMTX. The results showed a total of 95 metabolites that were found to be significantly (<i>p</i> < 0.05) modulated: either up- or downregulated in the HDMTX-treated group when compared with the control group. Using integrated pathway analysis we found these metabolites were associated with many important cardiac tissue metabolic pathways, such as the malate aspartate shuttle, taurine and hypotaurine metabolism, betaine metabolism, spermidine biosynthesis, and homocysteine degradation. Among them, L-arginine, homocysteine, and betaine were significantly upregulated, suggesting their possible association with cardiac tissue injury. Overall, we provided evidence for using untargeted metabolomics to identify novel metabolites associated with HDMTX cardiac toxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"294-302"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466898","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}
Gokul Sudhakaran, Karthikeyan Ramamurthy, V N Dhaareshwar, R Rajakrishnan, Ahmed Alfarhan, Jesu Arockiaraj
{"title":"Liquid mosquito repellent induces toxic effects in zebrafish.","authors":"Gokul Sudhakaran, Karthikeyan Ramamurthy, V N Dhaareshwar, R Rajakrishnan, Ahmed Alfarhan, Jesu Arockiaraj","doi":"10.1080/01480545.2024.2436511","DOIUrl":"10.1080/01480545.2024.2436511","url":null,"abstract":"<p><p>Mosquitoes serve as vectors for life-threatening parasitic diseases, presenting a continuous threat throughout human history. This has resulted in the extensive utilization of various mosquito repellents, including liquid mosquito repellents (LMRs), roll-ons, and topical creams. While these products demonstrate significant efficacy, the toxicological implications associated with their use are not yet fully understood and continue to be a subject of debate. The analysis conducted using gas chromatography-mass spectrometry (GC-MS) on LMR revealed the presence of 158 distinct compounds, among which were Piperazine 2,5-dimethyl propyl and a range of hydrocarbons. The analysis of network toxicology indicated that 78 of the examined compounds contravened Lipinski's rule of five and exhibited considerable overlap with target genes associated with lung cancer pathways, thereby highlighting potential concerns regarding their carcinogenic properties. The exposure of zebrafish embryos to LMR concentrations between 0.1 and 14 µg/mL resulted in developmental toxicity assays that demonstrated a dose-dependent escalation in mortality rates and the occurrence of morphological abnormalities, such as pericardial edema and skeletal deformities. Behavioral assays demonstrated a marked decrease in locomotor activity at elevated LMR concentrations, indicating potential neurotoxic effects. Biochemical analyses revealed elevated levels of reactive oxygen species (ROS), enhanced lipid peroxidation, and diminished glutathione, which are indicative of oxidative stress. Enzyme activity assays indicated a reduction in superoxide dismutase (SOD) and catalase (CAT) activities, alongside an increase in lactate dehydrogenase (LDH) activity, which suggests the occurrence of cellular damage. Analysis of gene expression demonstrated significant dysregulation in genes associated with oxidative stress (SOD1, CAT), inflammatory markers (TNF-α, IL-1β), apoptotic regulators (p53, bcl2), and neurobiological genes (brain-derived neurotrophic factor, bdnf). The results highlight the possible health hazards linked to LMR exposure, which manifest as developmental, biochemical, and genetic alterations in zebrafish embryos.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"404-415"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834588","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":"Di (2-ethyl hexyl) phthalate and its metabolite-induced metabolic syndrome: a review of molecular mechanisms.","authors":"Sorour Ashaari, Tannaz Jamialahmadi, Neal M Davies, Wael Almahmeed, Amirhossein Sahebkar","doi":"10.1080/01480545.2024.2405830","DOIUrl":"10.1080/01480545.2024.2405830","url":null,"abstract":"<p><strong>Objectives: </strong>Metabolic disorders, as multifactorial disorders, are induced by genetic susceptibility and exposure to environmental chemicals. Di (2-ethyl hexyl) phthalate (DEHP), a ubiquitous plasticizer, is well known as an endocrine-disrupting chemical in living organisms. In recent decades, researchers have focused on the potential of DEHP and its main metabolite (Mono (2-ethylhexyl) phthalate) (MEHP) to induce metabolic disorders. In the present review, we aimed to summarize studies regarding DEHP and MEHP-induced Metabolic syndrome (MetS) as well as address the involved mechanisms.</p><p><strong>Methods: </strong>A search has been carried out in Google Scholar, PubMed, Scopus, and Web of Science databases using appropriate keywords including 'Metabolic syndrome' or 'Metabolic disorder' or 'Obesity' or 'Hyperglycemia' or 'Hyperlipidemia' or 'Hypertension' or 'Non-alcoholic fatty liver disease' and 'DEHP' or 'Di (2-ethyl hexyl) phthalate' or 'Bis(2-ethylhexyl) phthalate' or 'MEHP' or 'Mono (2-ethylhexyl) phthalate'. Studies were chosen based on inclusion and exclusion criteria. Inclusion criteria are in vitro, in vivo, epidemiological studies, and English-written studies. Exclusion criteria are lack of access to the full text of studies, editorial articles, review articles, and conference articles.</p><p><strong>Results: </strong>Animal studies indicate that DEHP and MEHP disrupt insulin hemostasis, increase glucose content, and induce hyperlipidemia and hypertension as well as obesity, which could lead to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). DEHP and its metabolite induce such effects directly through influence on nuclear receptors such as peroxisome proliferator-activated receptors (PPARs) or indirectly through reactive oxygen species (ROS) production. Both events led to the disruption of several molecular signaling pathways and subsequently metabolic syndrome (MetS). Furthermore, epidemiological studies showed that there was a correlation between DEHP metabolites levels and obesity, hyperglycemia, and hypertension.</p><p><strong>Conclusions: </strong>According to studies, DEHP and its main metabolite have the potential to induce MetS by involving various molecular mechanisms. Epidemiological studies concerning the association of DEHP and MetS in humans are not sufficient. Therefore, more studies are needed in this regard.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"325-343"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343598","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}
Ana P Cuzziol Boccioni, Rafael C Lajmanovich, Andrés M Attademo, German Lener, Carlos R Lien-Medrano, María Fernanda Simoniello, Maria Rosa Repetti, Paola M Peltzer
{"title":"Toxicity of pesticide cocktails in amphibian larvae: understanding the impact of agricultural activity on aquatic ecosystems in the Salado River basin, Argentina.","authors":"Ana P Cuzziol Boccioni, Rafael C Lajmanovich, Andrés M Attademo, German Lener, Carlos R Lien-Medrano, María Fernanda Simoniello, Maria Rosa Repetti, Paola M Peltzer","doi":"10.1080/01480545.2024.2412023","DOIUrl":"10.1080/01480545.2024.2412023","url":null,"abstract":"<p><p>Aquatic communities are increasingly exposed to complex mixtures of contaminants, mainly pesticides due to the impact of agricultural activity. The aim of this study was to evaluate the toxicity of an eight-pesticide cocktail on larvae of the South American common toad, <i>Rinella arenarum</i>. The cocktail represents a realistic mixture of insecticides (cypermethrin, chlorpyrifos and lambda-cyhalothrin), herbicides (glyphosate, glufosinate ammonium, prometryn and metolachlor), and a fungicide (pyraclostrobin) previously found in aquatic organisms (<i>Prochilodus lineatus</i>) from the Salado River Basin, an area with strong agricultural pressure. Computational simulations through the Density Functional Tight-Binding method indicated a strong spontaneous trend toward the formation of the cocktail, suggesting that it may act as a novel xenobiotic entity in the environment. The cocktail effects were evaluated in early-developing and premetamorphic larvae, at feasible concentrations found in real scenarios. The mixture led to high mortality and teratogenicity in early-developing larvae. Premetamorphic larvae showed endocrine disruption, oxidative stress, and impairments in detoxification and hepatic functioning. Neurotoxicity, genotoxicity, cardiotoxicity and high mortality under stress conditions were also observed in exposed larvae. This novel evaluation highlights the ecotoxicological risk for aquatic organisms exposed to complex mixtures and underscores the need to consider cocktail effects in studies regarding ecosystems health.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"247-265"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460507","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":"Use of agrochemicals resulted in anemia and inflammation among farmers in Fako Division, Cameroon.","authors":"Christian Fusi Suh, Faustin Pascal Tsagué Manfo, Edouard Akono Nantia, Ndie Ngalame Dionysius, Jude Nkeng Fombele, Daisy Lum Suh, Etienne Philemon Atabonkeng, Paul Fewou Moundipa, Fidelis Cho-Ngwa","doi":"10.1080/01480545.2024.2429629","DOIUrl":"10.1080/01480545.2024.2429629","url":null,"abstract":"<p><p>The use of agrochemicals as plant growth regulators, pesticides, and soil fertilizers can result in insults among farmers and other non-targeted organisms. The adverse effects of agrochemicals are of global concern, though limited studies have delineated their toxicity on blood cells and inflammatory parameters in Fako division in Cameroon. This study examined the impact of occupational exposure on haematological and inflammatory parameters among farmers in Fako division. Briefly, 165 farmers who occupationally applied agrochemicals and a reference population of 75 non-farmers were interviewed on types of agrochemicals used, knowledge and safety during use of agrochemicals, as well as related symptoms of exposure. Serum cholinesterase (acetylcholinesterase and butyrylcholinesterase) activities were measured as biomarkers of exposure to agrochemicals. Complete blood count and serum levels of interleukin-6 (IL-6) and nitric oxide (NO) were determined as haematological and inflammatory biomarkers. Results disclosed frequent use of insecticides, fungicides, herbicides and fertilizers with neglect of personal protective equipment. Reported symptoms of exposure to agrochemicals were consistent with decrease in cholinesterase activities. Exposure to agrochemicals decreased erythrocyte count and red cell distribution width, as well as increased mean cell volume, mean corpuscular hemoglobin, serum levels of NO and IL-6 in farmers; suggesting anemia and increased cellular inflammation. In conclusion, the use of agrochemicals resulted in inhibited cholinesterase activities, induced anemia, and promoted cell inflammation in farmers. These findings call for more sensitization and training of the farmers to minimize agrochemical exposure and related health hazards.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"354-366"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750338","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}
S Madesh, Gokul Sudhakaran, Karthikeyan Ramamurthy, M K Kathiravan, Mikhlid H Almutairi, Bader O Almutairi, Selvaraj Arokiyaraj, Ajay Guru, Jesu Arockiaraj
{"title":"Cadmium and ketoprofen accumulation influences aquatic ecosystem demonstrated using <i>in-vivo</i> zebrafish model.","authors":"S Madesh, Gokul Sudhakaran, Karthikeyan Ramamurthy, M K Kathiravan, Mikhlid H Almutairi, Bader O Almutairi, Selvaraj Arokiyaraj, Ajay Guru, Jesu Arockiaraj","doi":"10.1080/01480545.2024.2364240","DOIUrl":"10.1080/01480545.2024.2364240","url":null,"abstract":"<p><p>The growing concern about pollution and toxicity in aquatic as well as terrestrial organisms is predominantly caused due to waterborne exposure and poses a risk to environmental systems and human health. This study addresses the co-toxic effects of cadmium (Cd) and ketoprofen (KPF), representing heavy metal and pharmaceutical discharge pollutants, respectively, in aquatic ecosystems. A 96-h acute toxicity assessment was conducted using zebrafish embryos. The results indicated that high dosages of KPF (10, 15, and 100 µg/mL) and Cd (10 and 15 µg/mL) reduced survivability and caused concentration-dependent deformities such as scoliosis and yolk sac edema. These findings highlight the potential defects in development and metabolism, as evidenced by hemolysis tests demonstrating dose-dependent effects on blood cell integrity. Furthermore, this study employs adult zebrafish for a 42-day chronic exposure to Cd and KPF (10 and 100 µg/L) alone or combined (10 + 10 and 100 + 100 µg/L) to assess organ-specific Cd and KPF accumulation in tissue samples. Organ-specific accumulation patterns underscore complex interactions impacting respiratory, metabolic, and detoxification functions. Prolonged exposure induces reactive oxygen species formation, compromising antioxidant defense systems. Histological examinations reveal structural changes in gills, gastrointestinal, kidney, and liver tissues, suggesting impairments in respiratory, osmoregulatory, nutritional, and immune functions. This study emphasizes the importance of conducting extensive research on co-toxic effects to assist with environmental risk assessments and safeguard human health and aquatic ecosystems.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"231-246"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442316","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}