Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Protective Effects of Phoenixin-14 Administration Against Renal Ischemia/Reperfusion Injury in Rats","authors":"Samet Öz,&nbsp;Mehmet Refik Bahar,&nbsp;Güldeniz Şekerci,&nbsp;Aslı Taşlıdere,&nbsp;Suat Tekin","doi":"10.1002/jbt.70200","DOIUrl":"https://doi.org/10.1002/jbt.70200","url":null,"abstract":"<p>Phoenixin (PNX), identified in the rat hypothalamus in 2013, has two bioactive isoforms with 14 and 20 amino acids. Initially studied for its role in reproductive regulation, research has since shown that PNX also prevents visceral pain, enhances memory, and aids heart tissue recovery. However, its role in kidney tissue remains unclear. Due to its antioxidant properties, PNX may help reduce oxidative stress and cellular damage in organs. This study was designed to determine the potential protective effects of Phoenixin-14 (PNX-14) against renal ischemia/reperfusion (I/R)-induced injury in rats. 40 male <i>Wistar Albino</i> rats were divided into four groups: Control, I/R, PNX-14 (50 µg/kg), and PNX-14 (100 µg/kg) (<i>n</i> = 10). All groups except the control group underwent 45 min of bilateral ischemia followed by 24 h of reperfusion. PNX-14 (50 and 100 μg/kg, intraperitoneally) was administered 1 h before induction of ischemia. Both doses of PNX-14 reduced the levels of acute kidney injury markers (blood urea nitrogen and creatinine) in blood tissue (<i>p</i> &lt; 0.05). PNX-14 increased the activity of antioxidant enzymes (superoxide dismutase and catalase) and the levels of glutathione, while reducing malondialdehyde (<i>p</i> &lt; 0.05). Histological evaluation of the I/R group revealed significant histopathological findings, and it was found that PNX-14 administration improved these histological damages (<i>p</i> &lt; 0.05). These results suggest that PNX-14 provides protection against renal injury induced by I/R. After further studies, PNX-14 may be a new therapeutic strategy to prevent renal I/R injury.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530050","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":"The Protective Effects of Saxagliptin and Cilostazol in an Experimental Model of Cyclophosphamide-Induced Nephrotoxicity in Rats: Targeting iNOS/NF-kB and Nrf-2/HO-1 Pathways","authors":"Monira A. Seleem,&nbsp;Ola M. Salem,&nbsp;Eman Basha,&nbsp;Hoda A. Ibrahim,&nbsp;Amira Mostafa Elshamy,&nbsp;Asmaa R. Azzam,&nbsp;Radwa Ismail,&nbsp;Abdallah A. Homouda,&nbsp;Alaa Elkordy,&nbsp;Heba Faheem","doi":"10.1002/jbt.70196","DOIUrl":"https://doi.org/10.1002/jbt.70196","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclophosphamide (CYP) is an extensively used immunosuppressive drug and chemotherapeutic agent for various malignancies. Nevertheless, its use is limited due to adverse effects, including nephrotoxicity. Saxagliptin is a DPP4 inhibitor, while cilostazol serves as an antiplatelet agent. Their nephroprotective effects arise from antioxidant and anti-inflammatory properties. This study investigated the potential protective effects of Saxagliptin and Cilostazol in rats with kidney damage induced by CYP. Five equal groups of 50 male Wistar rats were randomly categorised as Group I (Control group), Group II: CYP untreated nephrotoxicity–induced group, Group III: Nephrotoxicity-induced group treated with saxagliptin, Group IV: Nephrotoxicity-induced group treated with cilostazol, and Group V: Nephrotoxicity-induced group treated with saxagliptin and cilostazol. Renal tissues and blood samples were collected for biochemical analysis of urea, creatinine, and acute kidney injury biomarkers, including Kim-1 and NGAL. Additionally, oxidative stress and inflammatory biomarkers such as GSH, MDA, TNF-α and IL-1β were assessed, along with gene expression of <i>Nrf-2/HO-1</i> and <i>NF-kB</i>. Immunohistochemical analysis of iNOS, and histopathological study were also conducted. Saxagliptin and cilostazol ameliorated the nephrotoxicity induced by CYP, as indicated by improvements in urea, creatinine, and acute kidney injury biomarkers Kim-1 and NGAL. Furthermore, there was a decrease in oxidative stress via the upregulation of <i>Nrf-2/HO-1</i>, increased levels of GSH, downregulation of MDA and decreased inflammation via the downregulation of TNF-α, IL-1β and iNOS/<i>NF-kB</i>. The combination of saxagliptin and cilostazol demonstrated a significant improvement compared to using each agent individually. The combination of Saxagliptin/Cilostazol is superior to monotherapy by either of each alone in preventing CYP-induced nephrotoxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530046","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":"Cross-Talk Signaling Between Non-Small Cell Lung Cancer Cell Lines and Fibroblasts Attenuates the Cytotoxic Effect of Cisplatin","authors":"Nouran Ebid,&nbsp;Marwa Sharaky,&nbsp;Abeer Elkhoely,&nbsp;Engy M. El Morsy,&nbsp;Sherif Y. Saad","doi":"10.1002/jbt.70201","DOIUrl":"https://doi.org/10.1002/jbt.70201","url":null,"abstract":"<div>\u0000 \u0000 <p>Fibroblasts represent one of the most crucial cell types in the tumor microenvironment (TME), playing a major role in chemoresistance development. This study investigated the ability of fibroblasts to alter the response of non-small cell lung cancer (NSCLC) cell lines to cisplatin exposure. A cytotoxicity assay was performed to determine the IC₅₀ of cisplatin using MTT. The assay was performed on NSCLC cell lines A549 and H1299 monocultures and co-cultures with fibroblasts. The co-culture was performed directly with the HSF cell line and indirectly through conditioned media. The ELISA technique was then used to determine the expression of biochemical markers at various time points of co-culture before and after cisplatin exposure. We observed a time-dependent evolution in the fibroblast-cancer cell interplay. Initially, fibroblast co-culture enhanced the cytotoxic effect of cisplatin, as reflected by decreased IC₅₀ values after 24 h of co-culture. However, prolonged co-culture durations (48–96 h) led to the emergence of cisplatin resistance, coinciding with increased IC₅₀ values and altered expression of key biochemical markers. The findings suggest that fibroblasts undergo a potential identity switch over time, transitioning from a tumor-restrictive to a tumor-promoting phenotype. This switch was associated with the activation of EGFR and FGF signaling pathways, increased expression of angiogenic and metastasis markers (e.g., VEGF, MMP2 &amp; MMP9), and inhibition of apoptosis (e.g., reduced caspase expression). Our results suggest that fibroblasts may initially potentiate the effect of cisplatin on NSCLC cells; however, in a time-dependent manner, fibroblast co-culture attenuates the cytotoxic efficacy of cisplatin.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530048","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":"Sarsasapogenin Inhibits HCT116 and Caco-2 Cell Malignancy and Tumor Growth in a Xenograft Mouse Model of Colorectal Cancer by Inactivating MAPK Signaling","authors":"Ping Pan,&nbsp;Zhen Zhang,&nbsp;Yu Xu,&nbsp;Fangfang Li,&nbsp;Qingle Yang,&nbsp;Bing Liang","doi":"10.1002/jbt.70189","DOIUrl":"https://doi.org/10.1002/jbt.70189","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Colorectal cancer (CRC) is a prevalent malignancy globally and holds the third position in terms of cancer-related mortality in the United States. The study aimed to explore the impact of sarsasapogenin (Sar), a natural component, on CRC cell behavior and the related mechanism. Caco-2 and HCT116 cells were treated with 0–40 μM Sar or 5-fluorouracil (5-FU) to compare their cytotoxicity. Then, the optimal concentration of Sar was identified for subsequent experiments, and CRC cells in the control group were treated with dimethyl sulfoxide (DMSO). Cell counting kit-8 assays, colony-forming assays, and flow cytometry analyses were carried out to measure cell viability, proliferation, and apoptosis, respectively. Cell migration and invasion were evaluated by Transwell assays. HCT116 cells were inoculated into nude mice to induce tumorigenesis, and oral gavage of Sar was performed when tumor volume reached 50–100 mm³. Immunohistochemistry was performed to measure Ki67, E-cadherin, Vimentin, and N-cadherin expression in mouse tumor tissues. Western blot analysis was performed to assess protein levels of factors related to apoptosis, epithelial-mesenchymal transition (EMT) and mitogen-activated protein kinase (MAPK) pathway in CRC cells or mouse tumor tissues. Results showed that Sar repressed CRC cell viability in a dose-dependent manner, and the IC50 of Sar is 9.53 and 9.69 μM in HCT116 cells and Caco-2 cells. The number of CRC cell colonies was significantly decreased by Sar compared with that in DMSO group (HCT116: 52 vs. 162; Caco-2: 46 vs. 146), while cell apoptotic rate was increased by Sar (20.41% and 20.78%) compared to that in response to DMSO treatment (5.26% and 5.65%). Sar led to significant upregulation of Bax and cleaved caspase-3 protein levels while reducing Bcl-2 protein level. The number of migrated cells was reduced by Sar treatment in comparison to those in the context of DMSO treatment (HCT116: 65 vs. 223; Caco-2: 32 vs. 168). The same inhibitory impact of Sar was found on the number of invaded cells (<i>p </i>&lt; 0.001). E-cadherin level was noticeably elevated while N-cadherin and vimentin levels were prominently lessened in Sar-treated CRC cells. For animal experiments, the size, growth rate, and weight of tumors were all repressed by Sar (<i>p </i>&lt; 0.001). Ki67 expression was reduced and the EMT process was obstructed in mouse tumors of the Sar group (<i>p </i>&lt; 0.001). Sar inhibited the activation of MAPK signaling both in CRC cells and mouse tumors (<i>p </i>&lt; 0.001). In conclusion, Sar represses HCT116 and Caco-2 cell proliferation, migration, invasion, and xenograft tumor growth while promoting CRC cell apoptosis by inactivating the MAPK signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497372","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":"Mitochondrial Quality Control and Melatonin: A Strategy Against Myocardial Injury","authors":"Nima Ghavamikia,&nbsp;Faranak Mehrnoosh,&nbsp;Farshad Zare,&nbsp;Payam Ali-khiavi,&nbsp;Ali Sinehsepehr,&nbsp;Yasaman Ghodsi Boushehri,&nbsp;Milad Vahedinezhad,&nbsp;Elham Abdollahi,&nbsp;Ahmed Hjazi,&nbsp;Siamak Aminnezhad,&nbsp;Hossein Saffarfar,&nbsp;Sina Hamzehzadeh,&nbsp;Mehrdad Nourizadeh,&nbsp;Sepideh KarkonShayan","doi":"10.1002/jbt.70194","DOIUrl":"https://doi.org/10.1002/jbt.70194","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin exhibits various biological functions, including regulation of circadian and endocrine rhythms, anti-inflammatory, and antioxidant effects. Aging and damaged mitochondria are major sources of oxidative stress (OS), and mitochondrial quality control (MQC) is crucial for maintaining normal mitochondrial function. Myocardial ischemia-reperfusion injury is a major complication that can arise during reperfusion therapy for coronary heart disease. However, effective intervention strategies are currently lacking. Mitochondrial dysfunction and OS are considered central mechanisms of myocardial reperfusion injury, with mitochondrial-targeted interventions being a potential treatment direction. Recent studies have shown that melatonin improves mitochondrial structure and function through multiple pathways. This review discusses the mechanisms by which melatonin ameliorates myocardial ischemia-reperfusion injury, focusing on MQC, and explores its potential applications in the prevention and treatment of myocardial ischemia-reperfusion injury.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497370","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":"Curcumin Restrains TGF-β2-Induced Proliferation, Migration, Invasion and EMT in Lens Epithelial Cells by Regulating FGF7/ZEB1 Axis","authors":"Jing He,&nbsp;Ping Xie,&nbsp;Yangjun Ou","doi":"10.1002/jbt.70191","DOIUrl":"https://doi.org/10.1002/jbt.70191","url":null,"abstract":"<div>\u0000 \u0000 <p>Posterior capsular opacification (PCO) is the most common complication after cataract surgery characterized by hyperproliferation, migration and epithelial-mesenchymal transition (EMT) in residual lens epithelial cells (LECs). Curcumin is a polyphenol compound possessing diverse pharmacological properties. Here, we investigated the functions and its potential mechanisms of curcumin in PCO using transforming growth factor beta2 (TGF-β2)-treated LECs. Cell phenotypes were analyzed using MTT, 5-thynyl-2′-deoxyuridine (EdU), transwell, and scratch assays, respectively. Levels of FGF7 (Fibroblast Growth Factor 7), ZEB1 (Zinc finger E-box binding homeobox 1), and EMT-related proteins were detected by qRT-PCR and western blot analysis. The protein interaction between FGF7 and ZEB1 was validated using Co-immunoprecipitation assay. Curcumin treatment weakened TGF-β2-induced proliferation, migration, invasion and EMT progression in LECs. The expression of FGF7 was boosted by curcumin in LECs. Functionally, FGF7 deficiency suppressed TGF-β2-induced proliferation, migration, invasion and EMT progression in LECs, and could reverse the suppressing action of curcumin on TGF-β2-induced LEC dysfunction. Mechanistically, FGF7 directly interacted with ZEB1, and curcumin could regulate ZEB1 expression via FGF7. Moreover, ZEB1 overexpression could abolish the protective effects of curcumin or FGF7 deficiency on LECs under TGF-β2 stimulation. In conclusion, curcumin protected LECs against TGF-β2-induced enhancement on the proliferation, migration, invasion and EMT process by regulating FGF7/ZEB1 axis, suggesting a new insight into the application of curcumin in PCO therapy.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497369","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":"Protective Effects of Galangin Against Cyclophosphamide-Induced Cardiotoxicity via Suppressing NF-κB and Improving Mitochondrial Biogenesis","authors":"Manar Ali Elsayed,&nbsp;Doaa A. Radwan,&nbsp;Hanem Mohamed Rabah,&nbsp;Hemat El-Sayed El-Horany,&nbsp;Nahla Anas Nasef,&nbsp;Rehab E. Abo El Gheit,&nbsp;Marwa N. Emam,&nbsp;Rasha Osama Elesawy,&nbsp;Walaa Elseady,&nbsp;Alia Mahmoud","doi":"10.1002/jbt.70193","DOIUrl":"https://doi.org/10.1002/jbt.70193","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclophosphamide (CYP) is an effective chemotherapeutic and immunosuppressive agent; however, its clinical application is limited by a variety of toxic side effects. Mitochondrial dysfunction has been associated with the pathogenesis of chemotherapy-induced cardiotoxicity. This work aimed to evaluate the possible protective effect of galangin (Gal) on CYP-induced cardiotoxicity, pointing to its ability to promote mitochondrial biogenesis. Thirty two male rats were allocated equally into four groups: control; Gal-treated; CYP-treated; and Gal + CYP-treated groups. Markers of cardiac injury, oxidative/antioxidant status, inflammation, apoptosis, and mitochondrial function were assessed in addition to histopathological and electrocardiographic (ECG) evaluation. The current results revealed that Gal treatment significantly attenuated the cardiac injury and retrieved the alterations in cardiac histopathology and ECG changes. Also, it restored redox balance, as evidenced by the alleviation of malondialdehyde (MDA) levels and increased glutathione peroxidase (GPx) activity. Gal activated the sirtuin (SIRT) 1/nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway, as indicated by upregulation of SIRT1, Nrf2, SIRT3, and mitochondrial transcription factor (TFAM), in addition to increased levels of superoxide dismutase 2 (SOD)2 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), together with increased activity of citrate synthase (CS), pointing to improved mitochondrial function. It ameliorated the inflammation and apoptosis-associated markers supported by biochemical and immunostaining data. Our study provided novel insights elucidating the mitigative potential of against CYP-induced cardiac oxidative damage, inflammation, apoptosis, and mitochondrial dysfunction by upregulating the SIRT1/Nrf2/SIRT3/PGC-1α/TFAM survival pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489914","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":"Unveiling Novel Targets in Lung Tumors for Enhanced Radiotherapy Efficacy: A Comprehensive Review","authors":"Faris Anad Muhammad,&nbsp;Ayat Hussein Adhab,&nbsp;Morug Salih Mahdi,&nbsp;Vicky Jain,&nbsp;Subbulakshmi Ganesan,&nbsp;Deepak Bhanot,&nbsp;K. Satyam Naidu,&nbsp;Sharnjeet Kaur,&nbsp;Aseel Salah Mansoor,&nbsp;Usama Kadem Radi,&nbsp;Nasr Saadoun Abd,&nbsp;Muthena Kariem","doi":"10.1002/jbt.70180","DOIUrl":"https://doi.org/10.1002/jbt.70180","url":null,"abstract":"<div>\u0000 \u0000 <p>Radiotherapy is a cornerstone of lung cancer management, though its efficacy is frequently undermined by intrinsic and acquired radioresistance. This review examines the complexity of lung tumors, highlighting their potential as a reservoir of novel targets for radiosensitization. Ionizing radiation (IR) primarily exerts its effects through oxidative damage and DNA double-strand breaks (DSBs). Lung cancer cells, however, develop mutations that enhance DNA damage response (DDR) and suppress cell death pathways. Additionally, interactions between tumor cells and tumor microenvironment (TME) components—including immune cells, stromal cells, and molecular mediators such as cytokines, chemokines, and growth factors—contribute to resistance against IR. Understanding these intricate relationships reveals potential targets to improve radiotherapy outcomes. Promising targets include DDR pathways, immunosuppressive cells and molecules, hypoxia, proangiogenic mediators, and other key signaling pathways. This review discusses emerging strategies, such as combining radiotherapy with immunomodulators, hypoxia and proangiogenic inhibitors, DDR-targeting agents, and other innovative approaches. By offering a comprehensive analysis of the lung TME, this review underscores opportunities to enhance radiotherapy effectiveness through targeted radiosensitization strategies.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475583","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":"Low-Power Blue LED Modulates NF-κB and Proinflammatory Cytokines in Doxorubicin-Treated MDA-MB-231 Cells","authors":"Adilson Fonseca Teixeira,&nbsp;Bruno Ricardo Barreto Pires,&nbsp;Carolina Panis,&nbsp;Andréa Monte-Alto-Costa,&nbsp;Adenilson de Souza da Fonseca,&nbsp;Andre Luiz Mencalha","doi":"10.1002/jbt.70192","DOIUrl":"https://doi.org/10.1002/jbt.70192","url":null,"abstract":"<div>\u0000 \u0000 <p>Doxorubicin is a crucial chemotherapy used in the treatment of triple-negative breast cancer (TNBC) patients, but elevated doxorubicin doses may induce therapeutic resistance. To overcome this limitation, we have previously established a photodynamic therapeutic (PDT)-like strategy that irradiates doxorubicin-treated cells with a low-power nonionizing blue LED device. This combined treatment increases the production of reactive oxygen species to promote cell death, consequently enabling reduced doxorubicin dosages. Yet, precisely determining the molecular mechanisms that drive this outcome is still required for advancing such PDT-like approach. Here, we aimed to correlate the expression of the inflammatory markers NF-κB, IL-8, IL-6, and IL-1β with the survival of TNBC cells submitted to our PDT-like protocol. Our results show that NF-κB/p65 nuclear levels were enhanced in MDA-MB-231 cells treated with doxorubicin and blue LED. Moreover, this PDT-like strategy increased IL-6 mRNA levels in MDA-MB-231 cells. IL-1β and IL-8 mRNA were upregulated in samples incubated with doxorubicin regardless of concomitant irradiation with blue LED. These results show that our PDT-like protocol is effective in elevating inflammatory signals, shedding light on the molecular mechanisms that underlie the efficacy of this innovative anticancer therapeutic approach.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475587","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":"Methyl Donor Ameliorates CCl4-Induced Nephrotoxicity by Inhibiting Oxidative Stress, Inflammation, and Fibrosis Through the Attenuation of Kidney Injury Molecule 1 and Neutrophil Gelatinase-Associated Lipocalin Expression","authors":"Nirmal Manhar,&nbsp;Sumeet Kumar Singh,&nbsp;Poonam Yadav,&nbsp;Manish Bishnolia,&nbsp;Amit Khurana,&nbsp;Jasvinder Singh Bhatti,&nbsp;Umashanker Navik","doi":"10.1002/jbt.70188","DOIUrl":"https://doi.org/10.1002/jbt.70188","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbon tetrachloride (CCl₄), a volatile organic compound, is harmful to multi-organs, including the liver, lungs, muscles, and kidneys. Methyl donors, such as methionine, choline, betaine, and folic acid, are vital to one-carbon metabolism and have great potential to alleviate oxidative stress and inflammation, thus mitigating disease onset. Hence, the current study aims to examine the therapeutic effect of methyl donors against CCl₄-induced nephrotoxicity. Nephrotoxicity was developed in male Sprague Dawley rats using CCl₄ at a dose of 1 mL/kg (4-week model induction) twice a week via the intraperitoneal route. Thereafter, methyl donor treatments through oral gavage were given for the next 6 weeks with a continuation of CCl₄ administration. Biochemical, oxidative stress parameters, histopathological, and qRT-PCR analyses were done at the completion of the 10-week. Biochemical analyses revealed that CCl₄ induces nephrotoxicity, as evidenced by increased urea and creatinine levels and decreased albumin levels. These detrimental effects were significantly ameliorated by methyl donor treatment. Moreover, CCl₄ decreased the antioxidant enzyme activity (superoxide dismutase; SOD and catalase; CAT) while increasing oxidative stress markers (malondialdehyde; MDA and nitrite). Methyl donor treatment effectively mitigated these oxidative changes. Histopathological analysis demonstrated the nephroprotective effect of methyl donors against CCl₄-induced nephrotoxicity, showing reduced tissue damage and protection of renal architecture. At the molecular level, methyl donor treatment alleviated the CCl₄-induced increase in kidney injury biomarkers (Kidney injury molecule 1; KIM-1 and Neutrophil gelatinase-associated lipocalin; NGAL), as well as inflammatory (IL-6 and TNF-α) and fibrosis-related genes (Acta-2 and TGF-β). In conclusion, our findings suggest that methyl donors possess anti-inflammatory and anti-fibrotic properties. They protect against CCl₄-induced oxidative damage to renal cells, likely due to their reactive oxygen species scavenging capabilities and their ability to restore key early renal injury biomarkers (KIM-1 and NGAL). Methyl donors hold great promise as a cutting-edge therapy approach for preventing CCl₄-induced nephrotoxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475590","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}