Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Crocin Ameliorates Testicular Damage in Type 1 Diabetic Rats: Role of Akt-Mediated Nrf-2 Activation.","authors":"Gözdenur Güneş, Neslihan Akarsu, Serap Sancar, Deniz Erol Kutucu, Kadriye Akgün Dar, Ayşegul Kapucu Yılmaz","doi":"10.1002/jbt.70890","DOIUrl":"https://doi.org/10.1002/jbt.70890","url":null,"abstract":"<p><p>Diabetes, a prevalent global concern, leads to severe complications, with an increasing number of diabetic individuals each year. Reproductive function disorders and infertility associated with diabetes primarily arises due to oxidative stress and germ cells loss. Studies have revealed anti-inflammatory, antioxidant, antidiabetic, and anticancer properties of crocin. Crocin effectively scavenges free radicals and shields cells against oxidative stress damage. In our study, we aimed to investigate the potential protective effects and pathways of crocin on diabetic testicular damage induced by streptozotocin (STZ) in rats. In our study, results indicated that crocin reduces diabetes-associated testicular tissue damage, diminishes oxidative stress, and enhances spermatogenesis. Crocin exhibited antiglycemic effects in diabetic rats and demonstrated antioxidant effects in testicular tissue. These protective effects were found to occur by stimulating the expression of antioxidant enzymes through the Akt mediated Nrf-2 pathway. These findings significantly contribute to understanding the potential therapeutic effects of crocin, particularly as a protective agent against reproductive dysfunction associated with diabetes.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70890"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebularine Boosts Imatinib Efficacy in Cells of Colorectal Cancer via Wnt-Survivin-P-Glycoprotein Pathway.","authors":"Yasmin M Attia, Abeer Elkhoely, Fatma M Abdelwahed, Samia A Shouman, Mervat M Omran","doi":"10.1002/jbt.70885","DOIUrl":"10.1002/jbt.70885","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains one of the leading causes of cancer mortality, with a poor survival rate of less than 15%. Imatinib (IM) and Zebularine (ZEB) alone have shown potential effects in CRC treatment, but their combination has not been thoroughly studied. This study investigates the potential effects of IM and ZEB in colon cancer cells to provide a novel therapeutic agent for managing CRC. Cell growth inhibition, oxidative stress markers, and cell cycle progression were assessed in HCT-116 cells treated with IM, ZEB, and their combinations. ZEB uptake levels were analyzed by LC-MS/MS, apoptosis was quantified by flow cytometry, and gene expression changes were analyzed by qPCR. The expression of metastatic markers, apoptotic regulators, and EGFR was assessed. Both IM and ZEB inhibited cell growth in a concentration-dependent manner, and their combination showed synergistic effects. The combination significantly enhanced oxidative stress. The combination therapy increased apoptosis and necrosis. Furthermore, the combination induced significant S-phase arrest in the cell cycle. The combination treatment reduced metastatic markers (MMP9, MMP2), and the apoptotic marker Caspase-9 was upregulated. Additionally, the Bcl-2 protein, a key regulator of apoptosis, was significantly downexpressed. Remarkably, the combination treatment showed significant inhibition in EGFR levels. Both IM and ZEB combination showed promise in the management of CRC by inducing oxidative stress, promoting apoptosis, and modulating critical genes involved in metastasis and apoptosis. Further investigation will be needed to verify their application in preclinical and clinical settings.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70885"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esketamine Exposure Affects Neurodevelopment and Glutamate-NMDAR Signaling in Zebrafish Larvae.","authors":"Jingyi Wang, Shuo Huang, Tingting Lin, Zhineng Fu, Zhenghong Zuo, Zhiyuan Chen, Chengyong He","doi":"10.1002/jbt.70839","DOIUrl":"10.1002/jbt.70839","url":null,"abstract":"<p><p>Esketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has become a preferred option for perioperative use in infants and young children with low compliance due to its rapid onset and convenient administration. However, concerns regarding its potential neurotoxic effects during development warrant further investigation. This study aimed to elucidate the impact of esketamine on neurodevelopment and function in zebrafish larvae. Five days post-fertilization (dpf) zebrafish larvae were exposed to esketamine at concentrations of 10 mg/L and 100 mg/L for 2 and 6 h. The results demonstrated that esketamine exposure induced hyperlocomotion and increased dark preference in the larvae. Additionally, it elevated glutamate levels and significantly altered the expression of genes related to NMDAR and neurodevelopment. N-methyl-D-aspartate (NMDA) is an agonist of the NMDAR that reverses esketamine-induced hyperactivity and manf overexpression. In conclusion, esketamine exerts discernible effects on neurodevelopment and function in zebrafish larvae, with glutamatergic signaling potentially serving as a key underlying mechanism. These findings provide novel insights into the potential effects of clinical use of esketamine in pediatric populations, facilitating its safer application.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70839"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indirubin Sensitizes Prostate Cancer to Docetaxel by Inhibiting Autophagy Through the circ-Vav3/miR-204-5p/MAPK1 Pathway.","authors":"Minghao Zheng, Gan Cai, Long Ma, Xian Wu, Qian Wang, Zhenhua Jin, Chen Zhu, Shuaiyu Niu, Yanpei Peng, Yan Xu, Jingyuan Tang, Yunfei Wei","doi":"10.1002/jbt.70884","DOIUrl":"https://doi.org/10.1002/jbt.70884","url":null,"abstract":"<p><p>Accumulating evidence indicates that indirubin exerts inhibitory effects on prostate cancer (PCa) progression. However, the role and underlying mechanisms of indirubin in sensitizing PCa to docetaxel remain unclear. CCK-8 assays were initially used to determine the effect of indirubin on enhancing docetaxel sensitivity in PCa cells. Following this, the expression levels of circ-Vav3 were quantified using quantitative real-time PCR (RT-qPCR) to evaluate its potential role in docetaxel resistance. Functional experiments, including flow cytometry-based apoptosis analysis and Transwell migration/invasion assays, were conducted to assess the impact of circ-Vav3 modulation and indirubin treatment on cell viability and behavior in response to docetaxel. Rescue experiments were subsequently performed to further confirm the regulatory effect of indirubin on circ-Vav3. Additionally, xenograft tumor models in nude mice were utilized to evaluate the therapeutic efficacy of indirubin in vivo. Mechanistic interactions between circ-Vav3, miR-204-5p, and MAPK1 were further investigated using RNA pulldown assays, luciferase reporter assays, and Western blot analyses. Indirubin enhanced the sensitivity of PCa cells to docetaxel by downregulating the expression of circ-Vav3, which was found to be significantly upregulated in docetaxel-resistant PCa cells. Silencing circ-Vav3 effectively reversed this resistance, as evidenced by increased apoptosis, reduced cell migration and invasion, and decreased autophagic activity. Notably, indirubin treatment suppressed circ-Vav3 expression and thereby restored docetaxel sensitivity both in vitro and in xenograft tumor models. Mechanistically, circ-Vav3 acted as a competing endogenous RNA (ceRNA) by sponging miR-204-5p, which led to the upregulation of the autophagy-related kinase MAPK1. Inhibition of MAPK1 effectively suppressed autophagy and re-sensitized docetaxel-resistant PCa cells, further confirming the critical regulatory role of the circ-Vav3/miR-204-5p/MAPK1 signaling axis in mediating chemoresistance. Our findings demonstrate that circ-Vav3 promotes docetaxel resistance in PCa by sponging miR-204-5p and subsequently activating MAPK1-mediated autophagy. Indirubin effectively restores chemosensitivity by targeting this regulatory pathway, offering a promising therapeutic strategy for overcoming chemoresistance in castration-resistant prostate cancer (CRPC).</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70884"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_RPPH1/miR-326 Axis Blocks Chronic Stress-Promoted Progression and Metastasis of Lung Adenocarcinoma.","authors":"Ying Xiang, Yangfeng Huang, Dan Zhao, Ke Jin, Jianmei Zhu, Ying Wang","doi":"10.1002/jbt.70870","DOIUrl":"https://doi.org/10.1002/jbt.70870","url":null,"abstract":"<p><p>Chronic stress resulted in poor prognosis of cancer patients in the clinic. This study aimed to explore the mechanism by which chronic stress promotes the progression of lung adenocarcinoma (LUAD) through circ_RPPH1/miR-326 axis. Chronic stress-induced LUAD in vitro and in vivo models were established in A549 cells and C57BL/6 male mice. Sucrose preference test (SPT) and forced-swimming test (FST) were used for in vivo model evaluation. qRT-PCR and western blot were used to detect mRNA and protein levels. Cell proliferation, migration and invasion were also evaluated. Luciferase reporter assay was for target gene verification. In A549 cells, acetylcholine (ACh)-induced chronic stress contributed to the upregulation of circ_RPPH1. circ_RPPH1 knockdown remitted the carcinogenic effect of chronic stress on A549 cells. circ_RPPH1 serves as a sponger of miR-326, and miR-326 downregulation neutralized the beneficial role against tumor cell function and EMT in vitro. In vivo, circ_RPPH1 knockdown reduced the tumor volume and EMT-related protein levels of tumor-bearing mice under chronic stress treatment, while miR-326 antagomir co-transfection neutralized the effect. LARP1 might be the target gene of circ_RPPH1/miR-326 axis in CUMS mice. circ_RPPH1/miR-326 axis was involved in chronic stress-promoted progression and metastasis of LUAD.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70870"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-371a-3p Overexpression Alleviates Cognitive Dysfunction Via Targeted Negative Regulation of FKBP5.","authors":"Zhenzhen Sun, Yanyan Sun, Yaqi Guo, Aijie Liu","doi":"10.1002/jbt.70873","DOIUrl":"https://doi.org/10.1002/jbt.70873","url":null,"abstract":"<p><p>The study aims to explore the role of miR-371a-3p in cognitive dysfunction and its underlying mechanisms. This research comprised 143 elderly orthopedic patients undergoing anesthesia. They were further categorized into POCD and NPOCD groups based on postoperative MoCA scores. The relative expression and predictive value of miR-371a-3p in POCD were analyzed. The effects of miR-371a-3p on cognitive dysfunction in rats were assessed by the MWM test. The impact of miR-371a-3p overexpression on cell viability, apoptosis, apoptosis-related genes, inflammatory response, oxidative stress, and ferroptosis-related factors was examined in sev-induced HT22 cells. The target relationship between miR-371a-3p and FKBP5 was validated via database and dual luciferase assays. miR-371a-3p was markedly downregulated in POCD patients. miR-371a-3p demonstrated good predictive efficacy for POCD. Agomir-371a-3p effectively shortened the escape latency period, prolonged the dwell time in the target quadrant, and increased the platform crossing frequency in sev-induced rats. Concurrently, low miR-371a-3p expression was discovered in rat hippocampal tissue and HT22 cells exposed to sev. miR-371a-3p overexpression mitigates the decrease in cell vitality and increased apoptosis in sev-induced HT22 cells, and improves the inflammatory response, oxidative stress, and ferroptosis. Mechanistically, miR-371a-3p targets and regulates FKBP5. FKBP5 overexpression reverses the effects of miR-371a-3p on sev-induced neuronal cell damage. miR-371a-3p is a promising predictive biomarker for POCD. Agomir-371a-3p ameliorates sev-induced cognitive dysfunction in rats. Overexpression of miR-371a-3p alleviates sev-induced cognitive dysfunction by targeting FKBP5, offering a novel therapeutic approach for POCD.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70873"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Analysis of Azole Derivatives Targeting the PI3K/AKT/mTOR Pathway With In Vitro Cytotoxicity and Autophagy Evaluation.","authors":"Rathika Regurajan, Merlin Sobia Poomani, Iyyadurai Mariappan, Venkatesh Subramanian, Muthumanickam Sankar, Boomi Pandi, Krishnaveni Muthan","doi":"10.1002/jbt.70859","DOIUrl":"https://doi.org/10.1002/jbt.70859","url":null,"abstract":"<p><p>This study aims to identify potential azole-derived inhibitors targeting the PI3K/AKT/mTOR signaling pathway involved in autophagy regulation and cancer progression. A structure-based virtual screening approach was employed using molecular docking, molecular dynamics (MD) simulations, and free energy calculations (MMGBSA and MMPBSA). The pharmacokinetic profiles and toxicity of lead compounds were assessed using ADMET analysis. In vitro validation was performed using MTT and MDC staining assays on MDA-MB-231 breast cancer cells.Among the screened compounds, KR4 demonstrated strong binding affinity towards all three kinases (-8.289, -5.222, and -6.331 kcal/mol) respectively with favorable pharmacokinetic properties. MD simulation confirmed the stability of the KR4-protein complexes, while post-MD MMPBSA analysis validated the binding energetics. In vitro studies revealed dose-dependent cytotoxicity of KR4 (IC₅₀ ≈ 39 µM) and induction of autophagy in treated cells. The integration of in silico and in vitro approaches highlights KR4 as a promising multi-target inhibitor of the PI3K/AKT/mTOR pathway with potential anti-cancer properties. These findings support further exploration of KR4 for therapeutic development.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70859"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alogliptin Attenuates Diclofenac-Induced Acute Kidney Injury Associated With Activation of the AKT/Nrf2-mediated Ferroptosis Pathway.","authors":"Mai El-Sayed Ghoneim, Mohamed H Noureldin, Ibrahim El Sayed, Yousra Y El Banna, Nermein F El Sayed","doi":"10.1002/jbt.70848","DOIUrl":"https://doi.org/10.1002/jbt.70848","url":null,"abstract":"<p><p>Ferroptosis, a regulated form of cell death, has emerged as a crucial player in acute kidney injury (AKI); yet its involvement in diclofenac (DIC)-induced nephrotoxicity remains poorly understood. Alogliptin, a dipeptidyl peptidase (DPP)-IV inhibitor, is known for its anti-inflammatory and antioxidant properties; however, its potential to counteract ferroptosis-driven renal damage has not been fully explored. This study, therefore, aims to investigate the role of ferroptosis in diclofenac-induced kidney injury and evaluate the potential renoprotective effect of alogliptin, along with revealing the underlying mechanism(s). Rats were randomly allocated into four groups that were treated with saline or alogliptin ( ± DIC) for 14 successive days. DIC administration resulted in significant kidney damage, as evidenced by remarkable rise in serum creatinine, urea, and renal content of kidney injury molecule-1, alongside notable histopathological changes. Alogliptin pretreatment markedly attenuated these alterations, restoring renal function and histoarchitecture. Furthermore, alogliptin offset DIC-triggered ferroptosis, as indicated by reduced renal iron content and ACSL4 levels, along with upregulation of ferritin, SLC7A11, and GPX4. Moreover, it alleviated renal lipid peroxidation (increased malondialdehyde), apoptosis (heightened caspase-3 and diminished Bcl-2 expression), oxidative stress (downregulated glutathione, superoxide dismutase), and inflammation (elevated IL-6 and TNF-α expressions) in a dose-dependent manner. The current study uncovers a novel renoprotective role for alogliptin in mitigating DIC-induced renal injury, potentially mediated by stimulating AKT/Nrf2/SCL7A11/GPX4 signaling axis, with subsequent dampening of lipid peroxidation and ferroptosis, besides its well-known, anti-inflammatory, and antiapoptotic actions. Finally, these findings provide compelling evidence for repurposing alogliptin in combating DIC-triggered kidney damage.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70848"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combating Cadmium-Induced Neurotoxicity, Oxidative Stress, and Inflammatory Pathways Using DOPA-31, a Dioxopiperidinamide Derivative in an In Vivo Zebrafish Model.","authors":"Santhanam Sanjai Dharshan, S Madesh, Karthikeyan Ramamurthy, Jeyalakshmi Radhakrishnan, Kaliraj Salamuthu, Mikhlid H Almutairi, Bader O Almutairi, S Karthick Raja Namasivayam, Kathiravan Muthu Kumaradoss, Jesu Arockiaraj","doi":"10.1002/jbt.70872","DOIUrl":"https://doi.org/10.1002/jbt.70872","url":null,"abstract":"<p><p>Cadmium (Cd), a prevalent environmental toxin and pollutant capable of causing neurodegenerative diseases (NDs) like Alzheimer's and Parkinson's, primarily through oxidative stress, calcium imbalance, and neuroinflammation-induced mechanisms. Cd exposure increases the level of reactive oxygen species (ROS) and disrupts neurotransmitters by lowering antioxidants, leading to neuron death. Cd exposure in zebrafish results in neurodegeneration, with motor, mental, and behavioral impairments. The efficacy of the DOPA-31 intervention at varying concentrations was evaluated through the behavioral tests, biochemical assays for antioxidant enzyme activities (SOD, CAT, GSH, MDA), and histopathological analysis. Additionally, the alterations in expression levels of inflammation (tnf-α, il-1β) and neuroprotective (bdnf, syn2a) genes were also assessed. The Cd exposure exhibited the major deficits in the key behavioral parameters (motor, anxiety, and cognitive impairment). It disrupted antioxidant enzyme activity, increased lipid peroxidation, and elevated acetyl cholinesterase (AChE) activity, leading to cholinergic dysfunction. Histopathology showed extensive neuronal damage and amyloid-like protein aggregation. DOPA-31 at a 20 µM concentration, substantially exhibited antioxidant and AChE activity by reducing oxidative stress and improving motor and cognitive functions. Molecular analysis of DOPA-31 treatment showed significant downregulation of pro-inflammatory markers and upregulation of neuroprotective factors. In addition, DOPA-31 restored behavioral changes by potentially mitigating neuronal damage and protein aggregation caused by the Cd-induced neurotoxicity. This research investigation suggests the novel drug candidate DOPA-31 as a preliminary treatment for Neurodegenerative Disorder (NDD)-like features and warrants further exploration in higher animal models to assess clinical relevance.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70872"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin and Quercetin Co-Treatment Attenuates Hepatic Damage in Diabetic Rats by Mitigating Oxidative Stress and Inflammation.","authors":"Érique Ricardo Alves, Jaiurte Gomes Martins da Silva, Ismaela Maria Ferreira de Melo, Laís Caroline da Silva Santos, Marcelle Mariana Sales de França, Clovis Lapa Neto, Vanessa Bischoff Medina, Francisco de Assis Leite Souza, Leucio Duarte Vieira, Álvaro Aguiar Coelho Teixeira, Valéria Wanderley Teixeira","doi":"10.1002/jbt.70855","DOIUrl":"https://doi.org/10.1002/jbt.70855","url":null,"abstract":"<p><p>Liver complications in diabetes are very common, contributing to a high mortality rate, making it essential to develop strategies to minimize this damage. We analyzed the effect of treatment with quercetin and melatonin on the liver of diabetic rats. The following groups were formed: GC-non-diabetic rats; GD-diabetic rats; GDI-diabetic rats treated with insulin; GDM-diabetic rats treated with melatonin; GDQ-diabetic rats treated with quercetin; and GDQM-diabetic rats treated with quercetin/melatonin. Insulin (5 U/day), melatonin (10 mg/kg), and quercetin (40 mg/kg) were administered for 30 days after confirmation of diabetes. Weight, histology, immunohistochemistry (IL-6, TNF-α, and IL-10), biochemistry (glycemia, AST, and ALT), morphometry, and oxidative stress were evaluated. Only animals in the GDI (89.50 ± 4.92 mg/dL) and GDM (90.75 ± 3.88 mg/dL) groups showed similar blood glucose levels to the GC group (87.50 ± 7.14 mg/dL). Liver weight was higher in the GD group (12.44 ± 1.55 g). In the GD group, TBARS levels were elevated (3.10 ± 0.93 nmol/mg), and there was a reduction in GSH (12.90 ± 1.03 nmol/mg). In GD, there was an increase in the percentage of lobular parenchyma (95.00 ± 0.90) and a reduction in non-lobular parenchyma (5.00 ± 0.45). In the diabetic group, hydropic degeneration of hepatocytes and multifocal areas of coagulative necrosis were observed. AST (88.95 ± 11.45 U/L) and ALT (68.38 ± 1.79 U/L) were elevated. IL-6 and TNF-α were elevated in GD, while IL-10 was reduced. It is concluded that treatment with melatonin and quercetin, alone or in combination, may be an adjunctive alternative in protecting the liver against diabetic complications in rats.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70855"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}