Toxicology Mechanisms and Methods最新文献

{"title":"A microvolume protocol for catalase activity.","authors":"Beatriz Corrêa da Rocha, Marcos Trindade da Rosa Rosa, João Batista Teixeira da Rocha, Elgion Lucio Silva Loreto","doi":"10.1080/15376516.2026.2645750","DOIUrl":"10.1080/15376516.2026.2645750","url":null,"abstract":"<p><p>We developed and validated a microvolume protocol for measuring catalase (CAT) activity using a NanoDrop spectrophotometer, enabling reliable quantification with as little as 2 µL of sample. This methodology provides an efficient alternative to conventional assays that require substantially larger volumes and is particularly suited for studies with limited biological material, such as small organisms (<i>Panagrellus redivivus</i> and <i>Caenorhabditis elegans</i>) or specific organs of <i>Drosophila</i>. Our results demonstrate that the protocol accurately evaluates CAT activity, reflecting the physiological and metabolic characteristics of the analyzed tissues. To ensure specificity, CAT inhibitors and protein denaturation controls were employed. Overall, this methodology expands experimental possibilities for assessing enzymatic activity in reduced biological models and investigating their responses to oxidative stress.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"879-889"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782019","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":"Cisplatin-induced renal toxicity: an integrated view of molecular pathways and emerging therapeutic targets-a comprehensive review.","authors":"Naveen Vijiyakumar, Sabina Evan Prince","doi":"10.1080/15376516.2026.2656926","DOIUrl":"10.1080/15376516.2026.2656926","url":null,"abstract":"<p><p>Cisplatin is a widely used chemotherapeutic agent effective against a variety of solid tumors; however, its clinical utility is limited by dose-dependent nephrotoxicity. Cisplatin-induced renal injury involves a complex pathophysiology, including transporter-mediated uptake, biotransformation into reactive metabolites, oxidative stress, mitochondrial dysfunction, DNA damage, inflammation, and activation of cell death pathways such as apoptosis, necroptosis, and ferroptosis. Hydration therapy remains the primary clinical intervention; however, it provides limited protection, particularly in high-risk patient populations. Emerging biomarkers such as NGAL, KIM-1, cystatin C, and IL-18 enable earlier and more accurate detection of renal injury, whereas conventional markers, including serum creatinine and blood urea nitrogen (BUN), lack sensitivity for early diagnosis. Several pharmacological strategies targeting oxidative stress, inflammasome activation, mitochondrial dysfunction, and regulated cell death pathways are being investigated for their nephroprotective potential. Compounds such as MitoQ, ferrostatin-1, necrostatin-1, and NLRP3 inhibitors have demonstrated promising effects in preclinical models by attenuating cisplatin-induced renal damage. In addition, emerging approaches, including growth factors, stem cell-derived exosomes, and biomarker-guided therapeutic strategies, offer promising avenues for clinical translation. Overall, this review highlights the need for individualized, multi-targeted strategies to prevent and manage cisplatin-induced nephrotoxicity by integrating mechanistic insights, clinical challenges, and emerging therapeutic advances. Such approaches may improve cancer treatment outcomes while preserving renal function.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"828-843"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723784","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":"Real-time monitoring of microplastic accumulation in fish bodies using transparent goldfish revealed initial attack on the gill.","authors":"Md Abul Bashar, Saokat Ahamed, Takumi Mouri, Md Almamun Farid, Mohammad Maksudul Hassan, Yuna Uehara, Chihiro Yamamoto, Toshinobu Tokumoto","doi":"10.1080/15376516.2026.2648855","DOIUrl":"10.1080/15376516.2026.2648855","url":null,"abstract":"<p><p>To investigate the adverse effects of microplastics (MPs), we conducted an analysis using transparent goldfish (<i>Carassius auratus</i>). Transparent young goldfish were exposed to chronic toxicity concentration of fluorescently labeled microplastic beads (FMPs) and tracked their uptake into the body. During the four-week (28-day) treatment period, photographs of three parts of the goldfish were taken every week to track the localization of FMPs. FMPs were initially observed in the intestines, but from Day 14 onward, accumulation in the gills began to be observed. In the FMP-treated group, the number of individuals who died rapidly increased from Day 21. In deceased individuals, the accumulation of FMPs in the gills was prominent, suggesting that accumulation in the gills was the primary cause of death. Histological examination of the gill cells revealed that the epithelial cells of the secondary lamellae had died and that the central pillar cells and erythrocytes remained. TUNEL staining revealed a significant increase in cell death in the FMP-treated group. Confocal microscopic observation demonstrated that FMPs were bound to the cell surfaces and also invaded the cells. These results suggest that cell death is caused by the binding and invasion of MPs into gill cells. Based on these results, one of the adverse effects of MPs on fish is presumed to be a decrease in respiratory capacity due to impaired gill cell activity. This study has demonstrated that transparent goldfish can be used as a model for the toxicological analysis of various toxicants.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"919-930"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499780","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":"Arsenic-cadmium co-exposure rewires lipid-iron homeostasis to drive ferroptosis in human proximal tubular cells.","authors":"Yongguo Liu, Dengke Liu, Chengrong Zhang, Chuanqiu Zheng, Jianqiang Zhu, Shiyong Qi","doi":"10.1080/15376516.2026.2645333","DOIUrl":"10.1080/15376516.2026.2645333","url":null,"abstract":"<p><p>Arsenic (As) and cadmium (Cd) frequently co-occur in groundwater and preferentially target renal proximal tubules. Although each metal can independently induce ferroptosis-related processes, the integrated molecular responses to co-exposure remain incompletely understood. In this study, human HK-2 cells were exposed for 24 h to As (10 µM), Cd (10 µM), or their combination (5 µM + 5 µM). We evaluated ferroptosis- and oxidative stress-related gene expression, key protein markers, and lipid peroxidation. Combined exposure produced the most consistent transcriptional alterations across pathways involved in iron homeostasis, glutathione metabolism, lipid remodeling, mitochondrial function, autophagy, and NRF2 signaling. At the protein level, GPX4 and SLC7A11 were decreased, whereas ACSL4, PTGS2, and TFR1 were increased, accompanied by reduced ferritin and elevated LC3-II. Lipid peroxidation analysis further demonstrated a marked increase in oxidized lipid fractions in the co-exposure group. These findings indicate that arsenic and cadmium act synergistically to impair antioxidant defenses, enhance iron availability, and promote lipid peroxidation, thereby driving ferroptosis in renal epithelial cells. Targeting ferroptosis and iron metabolism may represent a promising strategy for mitigating mixed-metal-induced nephrotoxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"867-878"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475165","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":"Comparative stability assessment of synthetic cannabinoids in dry blood spots and blood using UHPLC-MS/MS: implications for forensic applications.","authors":"Kaja Tusiewicz, Paweł Szpot, Marcin Zawadzki","doi":"10.1080/15376516.2026.2652433","DOIUrl":"10.1080/15376516.2026.2652433","url":null,"abstract":"<p><strong>Objectives: </strong>Synthetic cannabinoids are the most numerous group of new psychoactive substances (NPSs) in Europe. The diversity and quantity of newly emerging synthetic cannabinoids make it difficult to monitor intoxications with these compounds, especially in view of their stability after biological material collection.</p><p><strong>Methods: </strong>In this study, 17 NPSs were analyzed to determine their stability in whole blood and dry blood spots (DBSs). The samples were stored at room temperature (DBS), 4 °C (DBS and whole blood), and -20 °C (whole blood). Analyses were performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. The stability study lasted 365 days, monitoring the degradation rate of analytes. Moreover, the effect of chemical structure on analyte stability was assessed.</p><p><strong>Results: </strong>Results proved that the stability of analytes depended on both storage conditions and their chemical structure. Four compounds showed better long-term stability in DBS samples, whereas seven of the tested compounds exhibited significantly better long-term stability in whole blood samples.</p><p><strong>Conclusions: </strong>Studies indicate a strong correlation between the stability of synthetic cannabinoids and both their chemical structure and storage conditions. DBS cards can provide equal or enhanced stability compared to whole blood, which makes it advisable to collect biological material in both forms to help maximize analytical options in forensic and toxicological investigations.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"959-974"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574465","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":"From exposure to injury: signaling mechanisms of microplastic-induced renal toxicity: an extensive review.","authors":"Ankit Verma, Manju Sharma, Renu Kaushik, Mohd Vaseem, Ozair Alam, Abdullah Albaqami, Mohammad Firoz Alam, Tarique Anwer","doi":"10.1080/15376516.2026.2658737","DOIUrl":"10.1080/15376516.2026.2658737","url":null,"abstract":"<p><p>Environmental micro and nanoplastics (MNPs) have emerged as pervasive contaminants with growing implications for systemic toxicity and organ-specific pathophysiological outcomes. Among vulnerable organs, the kidney represents a critical target due to its high perfusion rate, filtration function and continuous exposure to circulating xenobiotics. This review provides a renal-focused integrative synthesis of current experimental and mechanistic evidence examining the potential association between environmental MNPs exposure to nephrotoxicity. A structured literature search was conducted across major scientific databases to identify studies describing toxicokinetic behavior, molecular signaling responses and renal functional outcomes associated with MNP exposure. Mechanistically, MNPs exposure has been associated with oxidative stress amplification, inflammatory signaling activation, mitochondrial dysfunction, endoplasmic reticulum stress, autophagy dysregulation and profibrotic remodeling, collectively contributing to nephron structural alterations and renal functional impairment. Comparative evidence from experimental models further suggest that renal toxicity may be influenced by exposure route, dose and physicochemical particle transformation, highlighting the complexity of real-world environmental risk assessment. Advances in analytical toxicology have enabled improved detection of MNPs in biological matrices; however, methodological limitations related to contamination control, nanoscale sensitivity and standardized biomonitoring protocols remain significant challenges. By integrating environmental exposure dynamics with renal pathophysiological endpoints, this review proposes a conceptual framework that may help explain how molecular signaling hierarchies to clinically relevant kidney injury progression. Understanding these interconnected mechanisms may facilitate identification of early diagnostic biomarkers, refinement of exposure assessment strategies, and development of targeted therapeutic interventions aimed at mitigating environmentally mediated renal disease risk.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"844-866"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781986","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":"Glioprotective effects of gM-CSF against glutamate-induced oxidative stress, genotoxicity, and inflammation in rat C6 cells.","authors":"Farzaneh Motafeghi, Ehsan Ghassemi Barghi, Jafar Gholami Gharab, Nasrin Ghassemi Barghi","doi":"10.1080/15376516.2026.2647926","DOIUrl":"10.1080/15376516.2026.2647926","url":null,"abstract":"<p><strong>Background: </strong>Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is primarily known for hematopoiesis but has recently shown potential neuroprotective properties. This study investigated the glioprotective mechanisms of GM-CSF against glutamate-induced excitotoxicity in a rat C6 glioma cell line by examining multiple intertwined pathways.</p><p><strong>Methods: </strong>The protective effects of GM-CSF against glutamate toxicity were evaluated using MTT, alkaline comet, and TUNEL assays to assess cell viability, genotoxicity, and apoptosis, respectively. Additionally, oxidative stress was monitored <i>via</i> intracellular ROS levels and antioxidant enzyme activities (SOD, CAT, GPx), while pro-inflammatory cytokine release was quantified by measuring TNF-α, IL-1β, and IL-6 concentrations. Furthermore, specific cellular mechanisms were investigated through assays quantifying ATP production, mitochondrial membrane potential and autophagosome quantification.</p><p><strong>Results: </strong>Glutamate exposure significantly compromised cell survival and induced severe oxidative stress, DNA damage, inflammation, ATP depletion, mitochondrial depolarization, and increased autophagosome formation. However, pretreatment with GM-CSF (10-60 ng/mL) exerted a robust, dose-dependent protective effect across all measured parameters. Specifically, GM-CSF significantly restored cell viability, antioxidant enzyme activities (SOD, CAT, GPx), suppressed ROS accumulation, reduced DNA fragmentation, inhibited pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and effectively inhibited apoptosis. Crucially, GM-CSF also preserved mitochondrial membrane potential, maintained cellular ATP levels, and suppressed glutamate-induced autophagosome accumulation, confirming its multifaceted mechanism.</p><p><strong>Conclusion: </strong>In conclusion, GM-CSF effectively mitigates glutamate-induced toxicity in C6 glioma cells by counteracting oxidative stress, preserving genomic integrity, suppressing pro-inflammatory cytokine release, inhibiting apoptosis, maintaining mitochondrial function, stabilizing energy metabolism, and modulating autophagy. These findings highlight the extensive protective mechanism of GM-CSF and support its potential as a therapeutic candidate for attenuating excitotoxic damage.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"890-903"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677056","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":"Repurposing of piracetam to alleviate doxorubicin-induced cardiotoxicity in rats: targeting TLR2/MyD88/AP-1/NF-κB and VEGF/eNOS signaling pathways.","authors":"Marwa Monier Mahmoud Refaie, Rehab Ahmed Rifaai, Asmaa A Hasan, Heba A Habib, Nardien Ekram Haliem Saleh, Hoda S Sherkawy, Eman Shaaban Mahmoud, Sayed Shehata, Enas Fathy, Olivia N Beshay","doi":"10.1080/15376516.2026.2651369","DOIUrl":"10.1080/15376516.2026.2651369","url":null,"abstract":"<p><p>Doxorubicin (DOXO) is a highly efficient antineoplastic agent, but its clinical usefulness faces major cardiotoxic hazards. Thus, current study aimed to investigate the novel potential ameliorative effect of piracetam (PIRA) against DOXO-induced cardiotoxicity in addition to highlight the role of toll-like receptor 2 (TLR2)/myeloid differentiation primary response 88 (MyD88)/activator protein-1 (AP-1)/nuclear factor kappa-B (NF-κB) and vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling cascades. Rats were allocated in a random manner into five equal groups as follows: control (CONT), PIRA.400, DOXO, DOXO+PIRA.400, and DOXO+PIRA.400 + Nω-nitro-L-arginine methylester (L-NAME). Different cardiac enzymes along with oxidative stress, inflammatory and apoptotic biomarkers were detected. Furthermore, examination of the histopathological alterations in the cardiac tissue was evaluated. DOXO administration remarkably elevated the levels of cardiac enzymes, heart/body weight ratio (%), malondialdehyde (MDA), and upregulated active caspase-3, TLR2/MyD88/AP-1/NF-κB signaling cascade but downregulated VEGF/eNOS pathway along with substantial histopathological alterations. However, levels of serum total antioxidant capacity (T-AOC) and tissue reduced glutathione (GSH) significantly diminished with DOXO administration. All biochemical, histological, and molecular changes were considerably alleviated by the PIRA.400 treatment relative to DOXO alone. Interestingly, findings detected reducing the cardioprotective impact of PIRA on concurrent pretreatment with L-NAME, indicating the crucial role of eNOS in modulating this protection. This study revealed that PIRA ameliorated the DOXO-evoked cardiotoxicity <i>via</i> modulation of TLR2/MyD88/AP-1/NF-κB as well as VEGF/eNOS signaling cascades.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"943-958"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522077","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":"Ertugliflozin ameliorates thioacetamide-induced renal injury by modulating Nrf2-mediated oxidative stress, TLR4/STAT3 inflammatory signaling, and YAP/TAZ fibrotic pathways.","authors":"Naif ALSuhaymi, Mahdi H Alsugoor, Passant E Moustafa, Yosra Assem Hussien, Mevidette Elmadani, Hany M Fayed, Rehab F Abdel-Rahman","doi":"10.1080/15376516.2026.2657569","DOIUrl":"10.1080/15376516.2026.2657569","url":null,"abstract":"<p><p>Kidney damage, often caused by oxidative stress and inflammation, can lead to renal failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including Ertugliflozin (Ertu), demonstrate renoprotective effects that may extend beyond glucose control. Our research studied the therapeutic potential and underlying mechanisms of Ertu against subchronic kidney injury in rats induced by TAA, focusing on the integrative crosstalk between oxidative stress, TLR4/STAT3 inflammation, and the YAP/TAZ fibrotic pathway, a previously unexplored axis for SGLT2 inhibitors in nephroprotection. Rats were divided into four groups: control, TAA-induced renal damage, and TAA-induced damage treated with Ertu (5 or 10 mg/kg). We assessed renal function (creatinine, urea), oxidative stress (GSH, MDA, Nrf2), inflammation (IL-1β, TNF-α, TLR4, STAT3/p-STAT3), and fibrosis (YAP1, TAZ, TGF-β1) in serum and renal tissue. Immunohistochemistry was performed to quantify TLR4 and Caspase-1 expression. TAA administration significantly induced renal dysfunction, oxidative stress, and inflammation, evidenced by elevated creatinine, urea, MDA, IL-1β, TNF-α, TLR4, and p-STAT3/STAT3 ratio, alongside depleted GSH and Nrf2. Fibrotic markers (YAP1, TAZ, TGF-β1) were also markedly upregulated. Ertu treatment, particularly at the 10 mg/kg dose, effectively reversed these alterations. It restored antioxidant defenses (GSH, Nrf2), suppressed inflammatory signaling (TLR4/IL-1β/TNF-α), normalized STAT3 activation, and downregulated profibrotic pathways. Histological improvements corroborated these biochemical findings. Ertugliflozin confers significant protection against renal damage caused by TAA by concurrently modulating oxidative stress, inflammation, and fibrotic signaling. These mechanistic findings underscore its potential as a repurposed therapeutic agent for subchronic kidney injury.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"989-1001"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723760","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":"Acrylamide-induced nephrotoxicity mediated through endoplasmic reticulum stress pathway in rat kidney: protective effect of 4-phenylbutyric acid.","authors":"Mohammed Nazish Quasmi, Dinesh Dhingra, Ashok Jangra","doi":"10.1080/15376516.2026.2656472","DOIUrl":"10.1080/15376516.2026.2656472","url":null,"abstract":"<p><p>The current study aims to explore the role of endoplasmic reticulum stress (ER stress) in acrylamide (ACR)-induced nephrotoxicity. In addition, the role of ER stress is pharmacologically validated by a chemical chaperone, 4-phenylbutyric acid (4-PBA). In the present study, 24 male Albino Wistar rats (<i>n</i> = 6) were randomly divided into four groups. The control group received normal saline orally (p.o.) for 4 weeks. The acrylamide toxic group received ACR (10 mg/kg, p.o. in normal saline) for 4 weeks. The 4-PBA treatment groups received ACR for 28 days and 4-PBA (500 mg/kg and 1000 mg/kg, p.o. in saline) for the last 14 days. On the 29^th day, rats were euthanized, and blood as well as kidney samples were collected. Renal function parameters along with oxido-nitrosative stress biomarkers in kidney were analyzed. Western blotting was used to quantify the protein expression of key ER stress indicators, and finally, histopathological examination was conducted. Findings from the study indicated that ACR markedly increased the levels of kidney function markers, renal oxido-nitrosative stress, upregulated protein expression of ER stress-related proteins and disrupted normal morphology as compared to the control group. However, 4-PBA treatment reduced oxido-nitrosative stress, improved renal functioning, downregulated ER stress-related proteins and recovered the distorted morphology of the rat's kidney. These findings suggest the significant role of ER stress in the progression of ACR-induced nephrotoxicity as well as the ameliorative effect of 4-PBA against ACR-induced nephrotoxicity. Moreover, our findings provide the first evidence that activation of the ER stress pathway plays a critical role in acrylamide-induced nephrotoxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"975-988"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623829","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}