Journal of Applied Toxicology最新文献

{"title":"Oxidative Stress and Structural Damage Underlie Hepatic, Renal, and Intestinal Toxicity of Dodine in Rats Following Subacute Exposure.","authors":"Shabir Ahmad Bhat, Ruqeya Nazir, Haneef Mohammad Bhat","doi":"10.1002/jat.4923","DOIUrl":"https://doi.org/10.1002/jat.4923","url":null,"abstract":"<p><p>Pesticide use poses a significant threat to environmental integrity and animal health. Dodine (n-dodecylguanidine acetate), a widely used fungicide in horticulture, lacks comprehensive toxicological evaluation in animal systems, particularly with respect to systemic toxicity. This study investigated the multifaceted toxicity of dodine in Wistar rats, focusing on oxidative stress, biochemical alterations, tissue damage, and structural changes in liver, kidney, and intestinal tissues. Rats were divided into four groups (n = 6 per group) and administered dodine orally at 0 (control), 5, 20, and 80 mg/kg body weight daily for 30 days. Results revealed a significant increase in malondialdehyde (MDA) levels (p < 0.001) in all treated groups, indicating elevated lipid peroxidation. Concurrently, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) showed a dose-dependent reduction, particularly in the 20 and 80 mg/kg groups. Histopathological analysis revealed moderate to severe tissue degeneration, inflammation, and necrosis in hepatic, renal, and intestinal sections of medium- and high-dose groups. FTIR spectroscopy revealed molecular changes in protein and lipid functional groups, while scanning electron microscopy (SEM) showed significant ultrastructural damage in tissue morphology. Additionally, serum biomarkers including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, and urea levels were significantly elevated (p < 0.001), supporting evidence of hepatic and renal dysfunction. In conclusion, dodine induces dose-dependent oxidative damage and systemic toxicity in Wistar rats. These findings underscore the need for re-evaluating its safety and encourage further investigation, particularly at subchronic and environmentally relevant exposure levels, highlighting the need for stricter regulatory evaluation and further toxicological studies at environmentally relevant doses.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053609","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":"Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.","authors":"Michał Otręba, Łukasz Marek, Piotr Paduszyński, Jerzy Stojko, Anna Rzepecka-Stojko","doi":"10.1002/jat.4921","DOIUrl":"https://doi.org/10.1002/jat.4921","url":null,"abstract":"<p><p>Phenothiazine derivatives have been used for decades as antipsychotic drugs in multiple mental health and physical conditions treatment (schizophrenia, mania in bipolar disorder, and psychosis). Epidemiological studies have shown that people with schizophrenia are less likely to suffer from cancer, which indicates the ability of antipsychotics to inhibit the development of cancer cells. It is our third review about the impact of phenothiazine derivatives on cell death. Here, we focused on apoptosis. We selected 92 papers that investigated the effect of phenothiazine derivatives on the apoptosis process in normal and cancer cell lines. Chlorpromazine, fluphenazine, levomepromazine, mepazine, perphenazine, promazine, promethazine, thioridazine, trifluoperazine, and trifluoperazine analog (3dc) more often induce apoptosis in cancer cell lines, human hepatocytes, and lymphocytes, and the final effect depends on the type and concentration of drug used, the type of cell line, and the methodology used. The obtained results allow for a better understanding of the biological action of phenothiazine derivatives and will help reposition this group of drugs to cancer treatment, resulting in faster, safer, easier, and cheaper therapy.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029927","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":"Involvement of the PI3K/Nrf2 Pathway in Arsenic-Induced Endocrine and Thyroid Toxicity in Rats.","authors":"Xiaowei Ma, Yujian Zheng, Hongyun Li, Mei Yang, Jun Wu","doi":"10.1002/jat.4905","DOIUrl":"https://doi.org/10.1002/jat.4905","url":null,"abstract":"<p><p>Humans' exposure to arsenic (As) has been associated with the development of various diseases. Some health effects may be mediated by arsenic-induced toxicity to the thyroid and endocrine systems, but its underlying mechanisms remain unclear. The overall aim of our study was focused on using sodium arsenite (NaAsO₂)-exposed rats to investigate the involvement of the phosphatidylinositol 3-kinase (PI3K) and transcription factor NF-E2-related factor 2 (Nrf2) pathways in toxicity to the thyroid and endocrine systems. In our in vitro study, exposure of thyroid cells (a thyroid follicular epithelial cell line) to 0, 0.4, 0.8, and 3.2 μM. NaAsO₂ caused reduced triiodothyronine (T3) and thyroxine (T4) levels, significantly increased estrogen receptor alpha (ERα) and thyroid hormone receptor alpha (TRα) mRNA levels, reduced Kelch-like epichlorohydrin-associated protein-1 (Keap1) and AKT serine (AKT) mRNA expression, and increased Nrf2 and PI3K mRNA expression (p < 0.05). In the in vivo study, Wistar rats were treated with 0, 0.8, 4.0, and 20.0 mg/kg/d of NaAsO₂ for 20 weeks. The exposure caused dose-dependent histopathological changes in the thyroid, a significant increase in serum estradiol (E2), accompanied by alterations in thyroid hormone metabolism, as evidenced by decreased triiodothyronine (TG), T3, and T4 (p < 0.05). Additionally, mRNA expression levels of ERα and TRα were significantly altered in the thyroid tissues. Keap1, Nrf2, PI3K, and AKT mRNA expression levels were increased (p < 0.05). Specifically, exposure to NaAsO₂ disrupted normal thyroid functions by regulating the PI3K/Nrf2 pathway. Our findings indicate that NaAsO₂ exposure induced cytotoxicity and disrupted estrogen production both in vivo and in vitro investigations, leading to thyroid dysfunction through altered expression of the PI3K/Nrf2 pathway. These findings highlight the complex mechanisms through which arsenic disrupted thyroid function and endocrine homeostasis.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029937","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":"Acute Toxicity and Genotoxicity of cMoL, a Lectin From Moringa oleifera Seeds With Antifungal Activity Against Cryptococcus Strains.","authors":"Matheus Cavalcanti de Barros, Sávia Soraia Santana da Silva, Eduarda Pinto Gagliano, Alícia Natalie Silva Dos Santos, Leydianne Leite de Siqueira Patriota, Gustavo Ramos Salles Ferreira, Pollyanna Michelle da Silva, Simone da Paz Leôncio Alves, Julliano Matheus de Lima Maux, Jacinto da Costa Silva Neto, Fernanda Rafaelly Nascimento de Santana, Fabiana Aparecida Cavalcante Silva, Marilene Henning Vainstein, Luana Cassandra Breitenbach Barroso Coelho, Thâmarah de Albuquerque Lima, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva","doi":"10.1002/jat.4922","DOIUrl":"https://doi.org/10.1002/jat.4922","url":null,"abstract":"<p><p>Coagulant Moringa oleifera lectin (cMoL) is one of the compounds involved in the application of M. oleifera seeds for traditional water treatment methods. The present study highlights the new biotechnological potential of cMoL lectin as an antifungal agent against Cryptococcus neoformans B3501 and H99 and Cryptococcus gattii R265 strains. Acute toxicity and genotoxicity were assessed to provide information on security utilization. The antifungal activity was evaluated using the broth microdilution test, flow cytometry, antibiofilm activity, and synergistic effects with fluconazole. Acute toxicity was determined by administering a single dose of cMoL (200 mg/kg) to female Swiss albino mice and examining the following parameters: water and feed consumption, weight variation, blood hematological and biochemical parameters, serum cytokine levels, and histopathological analyses. Genotoxicity was assessed using comet assay and micronucleus test. cMoL inhibited the growth of all tested isolates, with a minimal inhibitory concentration of 7.5 μg/mL. Flow cytometry data showed that cMoL (7.5 μg/mL) significantly decreased cell viability by promoting necrosis. cMoL was not found to be an antibiofilm agent against Cryptococcus species; however, it acted synergistically with fluconazole against C. neoformans H99. cMoL (200 mg/kg) did not cause animal death or toxicity. No hematological, biochemical, histopathological, or genotoxic effects were observed. These results encourage the exploration of cMoL as a natural and safe antifungal agent against Cryptococcus.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029939","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":"Cell Toxicity and Autophagy in A549 Cells Treated With Surface-Functionalized Graphene Derivatives.","authors":"Tae Yun Park, Soo Young Kim, Chang Seok Park, Won Young Kim, Jae-Woo Jung, Jae-Yeol Kim, Jong Wook Shin","doi":"10.1002/jat.4869","DOIUrl":"https://doi.org/10.1002/jat.4869","url":null,"abstract":"<p><p>Graphene oxide and its derivatives have unique physical and chemical properties with applications in many different fields. However, their biological effects and mechanisms of intracellular toxicity have not been completely clarified. In this study, we investigated the cytotoxic and autophagic activities of graphene oxide and its derivatives in A549 human lung carcinoma cells. In the experimental procedure, A549 cells were treated with graphene oxide (GO), dodecylamine-oxidized graphene (DA-GO), reduced graphene oxide (rGO), and sodium dodecyl sulfate-reduced graphene oxide (SDS-rGO), and their cytotoxicity and protein expression levels were measured. Treating A549 cells with each type of graphene induced a concentration-dependent toxic effect on the cells, with no obvious cytotoxicity at low concentrations (32 𝜇g/mL). However, those treated with graphene with dodecylamine and sodium dodecyl sulfate functional groups exhibited high toxicity compared to its native form at high concentrations (> 100 𝜇g/mL). Cells exposed to the graphene materials exhibited increased conversion of LC3A/B-I to LC3A/B-II depending on concentration, indicating increased autophagy activity. They also exhibited reduced levels of mTOR protein, a negative regulator of autophagy, compared to a control group for all graphene materials. However, concentrations of beclin-1, a positive regulator of autophagy, were lower for all types of GO. These findings suggest that graphene exposure may induce beclin-1-independent autophagy in a noncanonical manner. We hypothesize that this may be a result of the involvement of apoptosis-associated substances that suppress autophagy. However, the exact mechanisms of the autophagy process are not well understood, and further research remains necessary.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023319","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":"Copper-Iron Oxide Nanoparticles Induce Apoptosis and Cell Cycle Arrest in Human Airway Epithelial Cells via Oxidative Stress and ROS Generation.","authors":"Maqsood A Siddiqui, Maqusood Ahamed, Quaiser Saquib, Javed Ahmad, Nida N Farshori, Ebtesam S Al-Sheddi, Mai M Al-Oqail, Shaza M Al-Massarani, Abdulaziz A Al-Khedhairy","doi":"10.1002/jat.4926","DOIUrl":"https://doi.org/10.1002/jat.4926","url":null,"abstract":"<p><p>Metal oxide nanoparticles are employed in various applications such as medicine, environmental remediation, molecular sensing, and drug delivery. However, large-scale commercial production and the use of smaller-sized nanoparticles increase the potential risk of toxicity to humans. Therefore, there is an urgent need to investigate the toxicity of nanomaterials. This study evaluated the toxic effects of copper-iron oxide nanoparticles (CIONPs) on human airway epithelial HEp-2 cells. The HEp-2 cells were exposed to different concentrations of CIONPs for 24 h. Various toxicological assays were used to assess cytotoxicity (MTT and neutral red assays), morphological changes, oxidative stress (GSH and LPO), ROS production, mitochondrial membrane dysfunction, cell cycle arrest, and mRNA expression of apoptotic marker genes (p53, caspase-3, caspase-9, Bax, and Bcl-2). The results revealed that 24-h exposure to CIONPs caused significant cytotoxicity and morphological damage in HEp-2 cells in a dose-dependent manner. Further cytotoxic doses of CIONPs influenced oxidative stress by decreasing GSH level and increasing LPO and ROS levels in HEp-2 cells. Moreover, exposure to CIONPs induced cell death by diminishing mitochondrial membrane potential and blocking the cell cycle in the SubG1 phase. Furthermore, CIONPs induced apoptosis by upregulating proapoptotic marker genes (p53, caspase-3, caspase-9, and Bax) and downregulating the antiapoptotic gene Bcl-2 in HEp-2 cells. Overall, the results of this study demonstrated that CIONPs are highly toxic to HEp-2 cells, indicating that the airway epithelium is one of the targets of CIONPs toxicity in humans. Therefore, these nanoparticles should be used with appropriate care.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029992","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":"Polystyrene Nanoparticles Induce Transcriptional Repression in TM4 Sertoli Cells.","authors":"Xin Huang, Kexuan He, Ying Jiang, Can Yang, Xiaoyu Liu, Qianyi Shen, Yunlong Liu, Junjie Fan, Jianrong Wu, Huajuan Ruan, Jun Yang, Yeting Hong","doi":"10.1002/jat.4925","DOIUrl":"https://doi.org/10.1002/jat.4925","url":null,"abstract":"<p><p>Polystyrene nanoparticles (PS-NPs) are prevalent environmental contaminants that can accumulate in biological tissues. This study investigates the effects of PS-NPs on TM4 cells, a Sertoli cell line crucial for maintaining the male spermatogenesis microenvironment.TM4 cells were exposed to PS-NPs (0-100 μg/mL) duration of 24 to 72 h. The cytotoxic effects of PS-NPs were assessed by measuring cell viability and membrane integrity. PS-NPs internalization and aggregation were visualized using transmission electron microscopy (TEM). Additionally, transcriptomic sequencing was conducted to identify differentially expressed genes (DEGs) after 48 h of exposure to 100 μg/mL PS-NPs, followed by a qRT-PCR assay to confirm the levels of DEGs. The results showed that PS-NPs were internalized and aggregated within the cytoplasm of TM4 cells. Exposure to PS-NPs did not significantly affect cell viability but compromised membrane integrity and significantly increased the ROS levels. Transcriptomic analysis identified a total of 382 DEGs, with 320 being downregulated and 62 upregulated. GO analysis revealed enrichment in transcriptional regulation processes, while GSEA indicated aberrant DNA methylation patterns. The expression level of the DNA demethylating regulator Tet3 was significantly reduced at both the mRNA and protein levels after exposure to PS-NPs. The levels of four genes (LOX, Zmynd12, Zfp354b, and Ccrl2) were confirmed by qRT-PCR, and their expression levels were consistent with the results after Tet3 knockdown. These findings suggest that PS-NPs induce transcriptional repression in TM4 cells, likely through the downregulation of Tet3, thereby disrupting the balance between DNA methylation and demethylation. This study provides insights into the epigenetic effects of PS-NPs on the male reproductive microenvironment and highlights potential implications for spermatogenesis.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029925","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":"Exploring the Impact of Microplastics and Nanoplastics on Macromolecular Structure and Functions.","authors":"Manka Marycleopha, Bachir Yaou Balarabe, Satish Kumar, Irédon Adjama","doi":"10.1002/jat.4915","DOIUrl":"https://doi.org/10.1002/jat.4915","url":null,"abstract":"<p><p>Microplastics and nanoplastics (MNPs) are common pollutants that engage with proteins, lipids, nucleic acids, and other biomolecules, damaging cell structure. This review goes beyond simply listing where MNPs are found to explore how they cause harm, detailing mechanisms such as oxidative stress, endocrine disruption, genotoxicity, protein misfolding, lipid membrane destabilization, and epigenetic changes. Propose an integrated mechanistic hypothesis connecting these processes via oxidative epigenetic feedback loops, size-dependent organelle targeting, and pollutant corona effects, with potential implications for cellular aging and transgenerational outcomes. Emphasize dose-response alignment, ecological relevance, and the biological significance of reported concentrations. Identify key knowledge gaps, especially regarding chronic low-dose exposures, co-pollutant interactions, and protein corona dynamics. This framework aims to enhance risk assessment, regulatory strategies, and mitigation of MNP-related ecological and human health risks.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006166","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":"Investigating the Potential Effects of 6PPDQ on Clear Cell Renal Cell Carcinoma via Network Toxicology and Molecular Docking Analysis With In Vitro Experimental Validation.","authors":"Yuanzhi Song, Siyuan Wang, Yifan Hong, Hao Yan, Yan Liu, Jinwen Mi, Zhongyao Zeng, Yang Liu, Miao Sun, Maolin Liu, Shengde Wu","doi":"10.1002/jat.4920","DOIUrl":"https://doi.org/10.1002/jat.4920","url":null,"abstract":"<p><p>N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPDQ), as a recently identified environmental toxicant, has garnered significant attention because of its widespread detection in ecosystems and human habitats. Emerging evidence highlights its potential detrimental effects on various organs. However, its carcinogenic potential remains poorly understood, particularly its role in clear cell renal cell carcinoma (ccRCC). This study seeks to elucidate the molecular mechanisms underlying 6PPDQ exposure and its potential contribution to ccRCC. Potential targets of 6PPDQ (1713) were predicted using PharmMapper, SwissTargetPrediction, SEA, and CTD databases. Integration with Genecard and GEO datasets (GSE53757) identified 2074 ccRCC-related genes and 3161 differentially expressed genes, yielding 70 overlapping targets. GO and KEGG enrichment analyses revealed significant associations with PI3K-AKT, JAK-STAT, and FoxO signaling pathways. PPI network constructed via STRING and analyzed with MCODE identified five hub genes (LGALS3, IL10, MMP9, LCN2, ALB), all with AUC values >0.7 in ROC analysis, indicating diagnostic potential. Single-gene GSEA suggested hub genes modulate ccRCC progression via IL6-JAK-STAT3 and PI3K-AKT-mTOR pathways. Immune infiltration analysis showed significant dysregulation of 20 immune cell types in ccRCC, with strong correlations between hub genes and immune cell infiltration levels. Molecular docking demonstrated good binding affinities (Vina score ≤ -5.0) between 6PPDQ and hub proteins. In 769-P human ccRCC cells treated with 1-2 μM 6PPDQ for 24 h, qPCR confirmed significant upregulation of all five hub genes (*p < 0.05). Through this research, we elucidated the relationship between 6PPDQ and ccRCC in specific important genes and signaling pathways, providing a basic platform for future research on the influence of 6PPDQ on ccRCC.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006158","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":"Ultrastructural Alterations in Melanopsis praemorsa (Linnaeus, 1758) (Gastropoda: Prosobranchia) Induced by Imidacloprid and the Protective Role of Ascorbic Acid.","authors":"Birgül Otludil, Lokman Damar","doi":"10.1002/jat.4919","DOIUrl":"https://doi.org/10.1002/jat.4919","url":null,"abstract":"<p><p>Imidacloprid, a neonicotinoid pesticide widely used for controlling agricultural pests, is known to exert toxic effects on non-target aquatic organisms. This study aimed to investigate the toxicological impact of imidacloprid and the potential protective effect of an antioxidant, ascorbic acid, in the freshwater snail Melanopsis praemorsa. Eight experimental groups were established: two controls; three groups exposed to imidacloprid at concentrations of 4.016, 40.16, and 80.32 μg/L; and three groups co-exposed to imidacloprid and ascorbic acid. Test organisms were maintained under defined conditions for 21 days. Following exposure, tissues from the digestive gland, mantle, and foot were dissected and examined at the ultrastructural level using transmission electron microscopy (TEM). Imidacloprid concentrations in the test medium were quantified via LC-MS/MS analysis. Ultrastructural examination revealed pronounced cytopathological alterations in imidacloprid-exposed groups, including cytoplasmic vacuolization, disrupted mitochondrial cristae, degeneration of the rough endoplasmic reticulum and Golgi apparatus, nuclear abnormalities, necrosis, and cellular lysis. In contrast, co-treatment with ascorbic acid led to a noticeable reduction in the severity of these lesions. These findings demonstrate that imidacloprid induces significant tissue damage in Melanopsis praemorsa, while the protective effect of ascorbic acid highlights the potential of this species as a promising bioindicator for monitoring aquatic pesticide contamination.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000590","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}