Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Cadmium Induces Kidney Damage by Regulating Ferroptosis.","authors":"Yamiao Fan, Linchen Ji, Tianqi Wang, Anqi Wang, Houjuan Xing","doi":"10.1002/jbt.70858","DOIUrl":"https://doi.org/10.1002/jbt.70858","url":null,"abstract":"<p><p>Cadmium (Cd) is a toxic heavy metal that accumulates in organisms and threatens health via the food chain. The kidney is a key target organ for Cd toxicity. Ferroptosis, a novel form of cell death distinct from apoptosis, necrosis, and autophagy, may be involved in Cd-induced kidney injury. Our study used in vivo and in vitro models to explore this link. Cd exposure caused pathological changes and increased Cd levels in pig kidneys, along with significant alterations in oxidative stress markers (ROS, MDA, LPO) and ferroptosis. In vitro, CdCl₂ exposure induced changes in mRNA and protein levels of oxidative stress and ferroptosis-related genes in PK-15 cells, increased intracellular iron, and decreased ATP. However, these effects were blocked by Nrf2 inhibitors (ML385). Our results suggested that Cd induced ferroptosis in renal cells via the Keap1-Nrf2-HO-1 pathway, revealing a new mechanism of Cd nephrotoxicity.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70858"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815459","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":"Schiff Base Derivatives as Carbonic Anhydrases and Cholinesterases Inhibitors: Molecular Docking and Anticancer Studies.","authors":"Zeynep Köksal, Pınar Güller, Fatma Sağır, Seda Ünlü, Fikriye Tuncel Elmalı","doi":"10.1002/jbt.70850","DOIUrl":"10.1002/jbt.70850","url":null,"abstract":"<p><p>This study investigated the inhibitory effects of a series of Schiff base derivatives, designated S1-S4, on human carbonic anhydrase isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) through in vitro and in silico analyses. Among the evaluated compounds, S3 emerged as the most potent multi-target inhibitor, demonstrating strong competitive inhibition of AChE (IC₅₀ = 12.88 ± 5.30 nM; Kᵢ = 7.55 ± 2.60 nM) and BuChE (IC₅₀ = 13.96 ± 2.02 nM; Kᵢ = 13.00 ± 6.80 nM). Furthermore, the compounds exhibited notable inhibitory activity against human carbonic anhydrase isoforms, with S3 inhibiting hCA I (IC50 = 7.90 ± 2.50 nM; Kᵢ = 14.0 ± 6.70 nM, non-competitive) and hCA II (IC50 = 23.00 ± 9.74 nM; Kᵢ = 10.20 ± 3.20 nM, competitive). While the binding affinities of the Schiff bases for the AChE receptor were predicted to be lower than that of Tacrine, the binding affinities of S2 and S4 for BuChE were estimated to be higher. For hCA I, the estimated binding energy of S1 was lower than that of acetazolamide, and for hCA II, the estimated binding energy of S2 was determined to be lower than that of acetazolamide. The cytotoxicity of the compounds was assessed against the aggressive PC3 prostate cancer cell line. Compound S4 emerged as the most potent cytotoxic agent, with a statistically significant IC50 value of 10.88 μM. Molecular docking studies corroborated the experimental findings, providing valuable insights into the underlying mechanisms of action. In conclusion, the objective of this study was to investigate the enzyme inhibitory and anticancer potential of synthesized Schiff bases using molecular docking analyses. The results indicate that compounds S3 and S4 exhibit strong inhibitory activity and may represent promising candidates for the development of novel therapeutic agents.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70850"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729086","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":"Monocrotophos-Induced Oxidative Stress Disrupts Locomotion and Metabolic Function in Drosophila melanogaster.","authors":"Kanchana Das, Abhratanu Ganguly, Sayantani Nanda, Gopal Biswas, Pritam Maitra, Prem Rajak, Moutushi Mandi","doi":"10.1002/jbt.70883","DOIUrl":"https://doi.org/10.1002/jbt.70883","url":null,"abstract":"<p><p>The study unveils potential toxic effects of a widespread organophosphate pesticide, monocrotophos, in a non-target model organism Drosophila melanogaster. Monocrotophos has been used in cotton, sugarcane, and paddy fields for many decades. Hence, a wide range of non-target organisms are get exposed to this pesticide. For the present study, five sub-lethal concentrations of monocrotophos were selected for chronic toxicity testing, which are below the determined LC₅₀ value (0.68 µg/mL). Drosophila larvae were exposed to different sub-lethal concentrations of monocrotophos through food media from their 1st instar stage to 3rd instar stage. The present study aims to explore the reactive oxygen species generation by thioredoxin reductase activity, glutathione content, along with H₂-DCFDA staining, which shows a significant amount of oxidative stress generation in both quantitative and qualitative means. MTT assay has been performed in brain tissue, which reflected a lower number of viable brain cells in treated larvae. Moreover, nuclear fragmentation in brain tissue by DAPI staining indicates the genotoxic potential of the test chemical. Acetylcholinesterase activity was found to be significantly decreased in the treated ones. Meanwhile, chronic sub-lethal exposure significantly reduced the metabolic activity, which was evident in cytosolic glucose content, glucose 6 phosphate dehydrogenase enzyme activity, and malate dehydrogenase enzyme activity. As both enzymes are closely linked with glucose metabolism, so decreased glucose level and both enzyme activity indicate altered metabolic status in cells. Poor brain health and altered metabolism status in monocrotophos-exposed larvae manifested impairment in crawling, phototaxic and embedding behavior in Drosophila. The overall study indicates monocrotophos mediated redox-imbalance, deficiency in metabolism, and compromised brain health untimely visible in poor behavioral responses. As this pesticide is able to contaminate different environmental compartments thus these hazardous effects will inevitably impact many non-target organisms. Observations of the present study can also be extrapolated to other non-target organisms as D. melanogaster shares significant homology with higher vertebrates.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70883"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815598","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":"In Vitro Studies on Induction of Ferroptosis Upon Low-level Exposure of Bisphenol A on Rat Erythrocytes.","authors":"M Naga Vaishnavi, Nidhi Srivastava, Ankita Sharma","doi":"10.1002/jbt.70867","DOIUrl":"https://doi.org/10.1002/jbt.70867","url":null,"abstract":"<p><p>Bisphenol A (BPA), is a xenoestrogen used in plastic manufacturing companies. Some countries are limiting the use of BPA. The widespread use of BPA has resulted in its accumulation in the natural environment. This compound is extensively utilised in various industrial products and is linked to harmful effects on both wildlife and human health. In recent years, extensive research has focused on ferroptosis-an iron-dependent form of programmed cell death characterised by lipid peroxidation. Also, several studies highlight the involvement of ferroptosis in mediating the toxic effects of environmental pollutants. This study aimed to deepen our understanding of BPA-induced ferroptosis by investing its impact on the antioxidant defence system, the structural integrity (as indicated by the rate of haemolysis), and the functionality of red blood cells. The research focused on evaluating the toxic effects of BPA through biochemical and haematological analyses conducted on RBCs of rats. To evaluate the involvement of ferroptotic cell death in BPA-induced toxicity, ferroptosis inducer RSL-3 and ferroptosis inhibitor Ferrostatin were used in the study either alone or in co-administration with highest concentration of BPA. The results showed that compared to the vehicle treated control group, after acute exposure of RBCs to BPA showed a notable decrease in Hb (haemoglobin) content and number of red blood cells. The ferroptotic markers viz. lipid peroxidation, GPx4 levels and ACSL4 activity were observed across all treatment groups. The results showed the possible involvement of ferroptosis on all these markers which were confirmed in the presence of ferroptosis inducer and inhibitor. Also, oxidative and nitrosative stress levels increased in a concentration-dependent manner of BPA. Furthermore, the activity of two important antioxidant enzymes; superoxide dismutase, and catalase lowered notably after BPA treatment. Results also showed significant morphological alterations, and increased membrane damage of RBC upon of BPA treatment. The study concludes that BPA exhibits oxidative stress, which may be one of the mechanisms causing RBC toxicity. The present study indicated that ferroptosis plays a key role in the progression of BPA-induced RBC toxicity; thus it can become a novel target in treatment of haemolysis.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70867"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815563","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":"Ameliorative Effects of Quercetin on Tartrazine-Induced Hepatotoxicity in Rats: Insights Into Body Weight, Caspase Signaling, Cytokine Storm, Oxidative Stress, and Hepatocellular Proliferation.","authors":"Bülent Aylaz, Zeynep Erdemli, Mehmet Gul, Nilufer Bulut, Emrah Zayman, Sezin Demirtas, Ezgi Karaaslan, Harika Gozukara Bag, Mehmet Erman Erdemli","doi":"10.1002/jbt.70882","DOIUrl":"https://doi.org/10.1002/jbt.70882","url":null,"abstract":"<p><p>Protective role of Quercetin against the possible harmful effects of Tartrazine, which is widely used. These doses have been studied for the first time in the literature. Rats were divided: Control, Tartrazine, Quercetin, and Tartrazine + Quercetin. The substances were administered for 30 days. Afterward, liver tissues and blood samples were collected and biochemically and histopathologically analyzed. An increase was noted in oxidant (MDA, SOD) and oxidative stress index parameters (TOS, OSI) while decreases were seen in antioxidant parameters (GSH, CAT, TAS), inflammation markers (TNF-α, IL-6), apoptosis (Caspase 3) and histopathological deterioration (heterochromatic with pyknotic nuclei, pericentral hepatocyte necrosis, and inflammatory cell infiltration) in liver tissue. There was also an increase in oxidative stress index, inflammation markers, and liver function tests (ALT, AST, ALP, Direct and Total Bilirubin) in serum samples of the tartrazine group. In the quercetin group, antioxidant parameters in liver tissue increased, whereas oxidant parameters, inflammation markers, and liver function tests in serum samples decreased. Improvements in both biochemical, blood, and histopathological parameters were observed with the concomitant administration of quercetin compared to the tartrazine group. Tartrazine caused hepatotoxicity by increasing oxidative stress, inflammation, and apoptosis in the liver tissues. Additionally, it led to widespread damage by elevating inflammation and worsening liver function test results in blood samples. Quercetin, however, showed strong antioxidant, anti-inflammatory, and apoptotic effects. We recommend daily use of quercetin to protect the liver from the harmful effects of tartrazine.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70882"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772332","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":"Sesamol As a Potential Anti-Fibrotic Agent Targeting ECM Dynamics in Oral Submucous Fibrosis.","authors":"Samreen Ramzan, Amreen Liaquat, Anum Islam, Shahrukh Khan, Talat Mirza, Shumaila Usman","doi":"10.1002/jbt.70863","DOIUrl":"https://doi.org/10.1002/jbt.70863","url":null,"abstract":"<p><p>Oral Submucous Fibrosis (OSMF) is a chronic, progressive, and potentially malignant condition of the oral cavity. Despite the availability of various therapeutic approaches, no single medication has demonstrated complete efficacy in reversing fibrosis or stopping the disease progression. Sesamol is a naturally occurring phenolic compound that is derived from sesame seeds and has strong anti-inflammatory, anticancer, and antioxidant effects. However, its anti-fibrotic and anti-proliferative properties in OSMF remain underexplored. Therefore, this study aimed to evaluate the anti-proliferative and anti-fibrotic effects of sesamol on the primary OSMF cell line. This was an In-Vitro Experimental study. The study was conducted in Ziauddin University, Clifton Campus, Karachi, from December 2024 to August 2025. The Primary OSMF fibroblasts (passages p8-p10) were treated with sesamol at its IC₅₀ concentration, and the standard drug was dexamethasone (IC₅₀). Cell viability was assessed using the MTT assay, and the anti-migration ability was examined through the scratch assay. Antifibrotic actions were also evaluated in Masson's trichrome staining (MTS), and quantification of fibrosis-related genes was performed to assess the results. Sesamol treatment suppressed OSMF cell viability in a dose-dependent manner, demonstrating cytotoxic and significant anti-proliferative effects. Scratch assay analysis showed sesamol demonstrated significant anti-migratory efficacy with delayed wound closure, whereas dexamethasone exerted an inhibitory effect. MTS showed that sesamol markedly reduced collagen buildup, highlighting its anti-fibrotic potential. Gene expression analysis showed that sesamol increased MMP-1 and MMP-2 while reducing COL1A2, α-SMA, and TGF-β1, promoting ECM degradation and suppression of fibrotic signaling. In contrast, dexamethasone modulated MMP expression and fibrosis-related genes. Dexamethasone, a standard clinically used corticosteroid for OSMF management, was used as the reference treatment to benchmark the molecular effects of sesamol. In conclusion, sesamol demonstrated a significant anti-proliferative, anti-migratory, and anti-fibrotic effect on primary OSMF fibroblasts, suggesting its potential to influence key profibrotic pathways. These findings highlight sesamol as a promising candidate for further preclinical studies in OSMF management.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70863"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772369","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":"Integrated Metabolomic and Biochemical Profiling of Benzodioxane-Derived Hydrazones Targeting Nrf2 to Mitigate Cadmium-Induced Metabolic Dysregulation.","authors":"Aisha Rafique, Muhammad Sajid Hamid Akash, Shagufta Kamal, Kanwal Rehman, Muhammad Usama Munir, Sehar Madni","doi":"10.1002/jbt.70869","DOIUrl":"https://doi.org/10.1002/jbt.70869","url":null,"abstract":"<p><p>Benzodioxane-derived hydrazones (BDHs) have emerged as promising antioxidant agents due to their redox-modulatory properties, structural versatility, and ability to activate cellular defense pathways. This study evaluated the protective potential of two BDH derivatives-MBDH (methoxy-substituted) and TBDH (thiophene-substituted)-against Cd-induced toxicity, a major environmental health concern associated with multi-organ dysfunction via oxidative stress and mitochondrial impairment. Using LC-MS/MS-based metabolomic profiling together with biochemical assays in a mouse model, we compared the efficacy of BDHs with that of ascorbic acid. Cd exposure resulted in significant metabolic disruption, including reduced levels of amino acids (serine, methionine), elevated lipid peroxidation products (ceramides, phospholipid fragments), and mitochondrial dysfunction. Ascorbic acid (AA) provided partial metabolic and histological protection. MBDH exhibited moderate effects by reducing lipid peroxidation markers and partially restoring some amino acid levels, with a hydroxylated metabolite detected at m/z 328. TBDH, however, demonstrated superior protection, with near-complete normalization of metabolic profiles, formation of a stable metabolite (m/z 304), and marked attenuation in lipid peroxidation. Additionally, TBDH activated the Nrf2 signaling pathway, increased intracellular glutathione levels, and significantly improved histopathology in the liver, brain, and pancreas. It also reduced the levels of systemic inflammatory markers such as CRP, ESR, and procalcitonin. The enhanced performance of TBDH is attributed to its thiophene moiety, which facilitates improved electron delocalization and redox potential. This study highlights TBDH as a potent Nrf2 activator and antioxidant agent capable of mitigating Cd-induced metabolic and oxidative damage, providing a strong basis for the development of BDH-based therapeutics targeting heavy metal toxicity and related oxidative stress disorders.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70869"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772378","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":"Insights Into the Ameliorative Effect of Diacerein on Cyclophosphamide-Induced Testicular Toxicity: Targeting TLR4/NF-κB/IL-1β Pathway.","authors":"Ayaat M Mohamed, Heba A Habib, Gehan H Heeba","doi":"10.1002/jbt.70795","DOIUrl":"https://doi.org/10.1002/jbt.70795","url":null,"abstract":"<p><p>Male infertility represents one of the most troublesome of cyclophosphamide (CYP), a frequent chemotherapeutic agent, restricting its clinical usage. Diacerein (DIA), an anthraquinone derivative inhibiting interleukin-1 beta (IL-1β), is often applied as an anti-inflammatory agent in managing osteoarthritis with antioxidant and anti-inflammatory potential, making it a hopeful therapeutic strategy for testicular dysfunction. This study was conducted to investigate the probable safeguarding afforded by DIA on CYP-induced testicular injury in male rats, pointing to the possible mechanisms involved in DIA protection. In a 14-day experiment, 32 adult male rats were involved in this study and distributed into four groups: control, DIA, CYP, and CYP + DIA groups. Diacerein opposed testicular damage caused by CYP, which is demonstrated by the improved histological construction and amelioration of the abnormalities in sperm indices and testosterone concentration. DIA enhanced the activity of antioxidant enzyme, superoxide dismutase, and reduced glutathione levels alongside minimized malondialdehyde and total nitrite content in the testes of CYP-challenged rats. In testicular tissues, DIA pretreatment counteracted the up-regulation in the toll-like receptor 4/nuclear factor-kappa B/IL-1β pathway-mediated inflammation. Moreover, DIA abrogated CYP-provoked apoptosis, as evident by down-regulated cleaved-caspase-3 expression. In summary, the results of this investigation reported that DIA's antioxidant, anti-inflammatory, and antiapoptotic impact mediated its protective influence against CYP-induced male organ toxicity.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70795"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772409","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":"Significant Role of Thrombospondin-2 in Acute Lung Injury and Its Underlying Molecular Mechanisms.","authors":"Yi Liu, Junxia Wang, Huilin Luo","doi":"10.1002/jbt.70842","DOIUrl":"https://doi.org/10.1002/jbt.70842","url":null,"abstract":"<p><p>Acute lung injury (ALI) is associated with high mortality. Thrombospondin-2 (THBS2), a member of the THBS family, has been implicated in multiple diseases, but its role in ALI remains unclear. The study aimed to explore the role of THBS2 in ALI and its regulatory mechanisms. A549 cells were treated with 1 μg/mL lipopolysaccharide (LPS) for 24 h to establish an in vitro cellular model of ALI. THBS2 siRNA was used to knockdown THBS2 and investigate its role. Changes in cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), and catalase (CAT) levels were quantified. Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-alpha (TNF-α) levels were measured by enzyme-linked immunosorbent assay. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine gene and protein expression, respectively. THBS2 expression was increased in LPS-induced A549 cells. LPS significantly reduced cell viability, enhanced cell apoptosis, increased cleaved caspase-3 expression and the cleaved caspase-3/caspase-3 ratio, increased ROS and MDA levels, decreased SOD and CAT activity, and promoted IL-6, IL-1β, and TNF-α levels in A549 cells. Meanwhile, LPS activated the toll-like receptor 4 (TLR4)/NF-κB pathway, but these changes were reversed by THBS2 siRNA. The results also demonstrated that TLR4 plasmid reversed the protective effects of THBS2 siRNA against LPS-induced injury in A549 cells. THBS2 was upregulated in ALI in vitro model, and its knockdown attenuated LPS-induced injury in A549 cells by inhibiting the TLR4/NF-κB signaling pathway.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70842"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772452","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":"Patulin Affects the Hydroxylation of Vitamin D by Downregulating 25-hydroxylase (CYP2R1) and 25-hydroxyvitamin D 1-alpha-hydroxylase (CYP27B1) Expression and Interfering Their Substrate Binding Sites.","authors":"Shangyun Lu, Jing Gao, Huixia Zhang, Chao Fan, Ziling Liu, Qi An, Mengge Ren, Yuchen Bai, Fubin Qiu","doi":"10.1002/jbt.70877","DOIUrl":"https://doi.org/10.1002/jbt.70877","url":null,"abstract":"<p><p>Patulin (PAT) is a mycotoxin that grows on various fruits and grains, and its toxicity research mainly focuses on organ toxicity. However, the research on its impact on nutritional metabolism is still unclear. Vitamin D is an important nutrient and has been reported to have multiple physiological functions. Vitamin D deficiency has been reported to be associated with the risk of developing diseases such as fatal cancers, autoimmune disorders, cardiovascular disease, neurocognitive function impairment, and type 2 diabetes. However, vitamin D need to be converted into biologically active forms through two steps of hydroxylation in the liver or kidney by 25-hydroxylase (CYP2R1) and 25-hydroxyvitamin D 1-alpha-hydroxylase (CYP27B1). In this study, we found that PAT can cause liver and kidney injury, and affect the levels of activated vitamin D products 25(OH)D and 1,25(OH)₂D. Specifically, we demonstrated that PAT affects the hydroxylation of vitamin D by downregulating 25-hydroxylase (CYP2R1) and 25-hydroxyvitamin D 1-alpha-hydroxylase (CYP27B1) expression and interfering their substrate binding sites. This study can provide a basis for a more comprehensive assessment of the impact of environmental pollution, food safety, and other issues on human health.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 5","pages":"e70877"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838319","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}