Chemico-Biological Interactions最新文献

{"title":"Erianin reverses 5-FU resistance by targeting CALM1/CAMKK2 and activating autophagy in colorectal cancer","authors":"Fangyuan Zhou ,&nbsp;Luorui Shang ,&nbsp;Jinxiao Li ,&nbsp;Mengqi Zhang ,&nbsp;Shuhan Wang ,&nbsp;Yuju Cai ,&nbsp;Qifeng Lin ,&nbsp;Haiyang Gao ,&nbsp;Shenglan Yang","doi":"10.1016/j.cbi.2025.111750","DOIUrl":"10.1016/j.cbi.2025.111750","url":null,"abstract":"<div><h3>Background</h3><div>Chemoresistance represents a significant factor contributing to the failure of clinical treatments in colorectal cancer (CRC), with resistance to 5-fluorouracil (5-FU) being notably prevalent. Erianin has demonstrated potential in reversing tumor resistance; however, its specific effects and underlying mechanisms in the context of 5-FU-resistant CRC require comprehensive validation.</div></div><div><h3>Methods</h3><div>The half-maximal inhibitory concentration (IC50) of Erianin and 5-FU was determined using the CCK8 assay. CRC cells resistant to 5-FU were induced by progressively increasing concentrations of 5-FU. Cellular proliferation, migration, and invasion were evaluated via 5-ethynyl-2′-deoxyuridine (EdU) assays, wound-healing assays, and Transwell Matrigel invasion assays. The expression levels of protein and mRNA expression levels for various molecules were quantified using Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Immunofluorescence assays were employed to assess the expression of autophagy-related markers. The <em>in vivo</em> therapeutic efficacy of Erianin was assessed using a xenograft tumor model.</div></div><div><h3>Results</h3><div>Erianin effectively reinstated the sensitivity of 5-FU-resistant CRC cells to 5-FU, significantly reducing tumor cell proliferation, migration, and invasion, as well as inhibiting xenograft tumor growth. Mechanistic investigations demonstrated that Erianin targets and binds to the calmodulin 1 (CALM1) protein, enhancing its stability and subsequently increasing the phosphorylation levels of CAMKK2. This interaction facilitates autophagy in 5-FU-resistant CRC cells, ultimately leading to tumor cell death.</div></div><div><h3>Conclusion</h3><div>Erianin sensitized the resistant CRC cells to 5-FU by activating the CALM1/CAMKK2 signaling pathway, thereby inducing autophagy. The combination of 5-FU and Erianin presents a promising therapeutic approach to enhance survival outcomes in patients with refractory CRC.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111750"},"PeriodicalIF":5.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HTR1D regulates the PI3K/Akt signaling pathway to impact glioblastoma development and resistance to temozolomide","authors":"Huanqi Zhang ,&nbsp;Ziyan Liu ,&nbsp;Jing Cheng ,&nbsp;Yiming Jiang ,&nbsp;Xiaoli Zheng ,&nbsp;Chong Zhang ,&nbsp;Yangling Li","doi":"10.1016/j.cbi.2025.111748","DOIUrl":"10.1016/j.cbi.2025.111748","url":null,"abstract":"<div><div>Glioblastoma (GBM), the most aggressive primary brain tumor, presents significant therapeutic challenges owing to limited treatment options beyond the cornerstone chemotherapy temozolomide (TMZ) and its intrinsic chemoresistance. This study elucidates additional mechanisms of the multimodal antidepressant vortioxetine in GBM, extending beyond the reported PI3K/Akt pathway modulation. RNA-sequencing analysis identified five potential vortioxetine-responsive targets in GBM cells: <em>SCN5A</em>, <em>HTR1D</em>, <em>SLC6A9</em>, <em>KIF11</em>, and <em>ADRB2</em>. Notably, only <em>HTR1D</em> overexpression correlated with poor disease-free survival in GBM patients. Vortioxetine-mediated HTR1D suppression suggests its potential role as an HTR1D inhibitor in GBM progression. HTR1D-overexpressing GBM cells exhibited enhanced proliferative and migratory capacities. LinkedOmics database analysis revealed the HTR1D regulation on PI3K/Akt axis, a dominant signaling pathway showing significant positive correlation with TMZ resistance. Crucially, HTR1D knockdown enhanced TMZ sensitivity in GBM cells. Moreover, the TMZ-vortioxetine combination demonstrated marked synergistic anti-tumor effects concomitant with HTR1D suppression. <em>In vivo</em>, the TMZ-vortioxetine combination more effectively suppressed GBM proliferation than either agent alone. Collectively, these findings identify HTR1D as a novel vortioxetine target in GBM that modulates proliferation, metastasis, and TMZ resistance via PI3K/Akt signaling. This study provides convincing preclinical evidence for TMZ-vortioxetine combination therapy, proposing both a new therapeutic target and a viable strategy to circumvent TMZ resistance in GBM.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111748"},"PeriodicalIF":5.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theaflavin 3,3′-digallate suppresses metastasis and reduces insulin-like growth factor-1-induced cancer stemness and invasiveness in human melanoma cells","authors":"Ju-Pi Li ,&nbsp;Yi-Hsien Hsieh ,&nbsp;Yi-Hsun Lee ,&nbsp;Wen-Yi Tsai ,&nbsp;Shun-Fa Yang ,&nbsp;Yih-Shou Hsieh ,&nbsp;Pei-Ni Chen","doi":"10.1016/j.cbi.2025.111751","DOIUrl":"10.1016/j.cbi.2025.111751","url":null,"abstract":"<div><div>Theaflavin 3,3′-digallate (TF3), a flavonoid compound, exerts antidiabetic effects, induces apoptosis, and suppresses cancer growth. However, its effects on melanoma metastasis and insulin-like growth factor 1 (IGF-1)-induced cancer stemness remain largely unexplored. This study explored key molecular signaling pathways underlying the antitumor and antimetastatic activities of TF3 in melanoma. The antimetastatic potential of TF3, as well as its impact on IGF-1-induced cancer stemness, were evaluated using wound healing assays, gelatin zymography, Matrigel invasion assays, sphere formation assays, and Western blotting. Its antiangiogenic and antimetastatic activities were further examined in vivo using subcutaneous xenograft and tail vein injection mouse models. TF3 significantly inhibited cell migration, invasion, and matrix metalloproteinase (MMP) activity in A 375 and A2058 melanoma cells. It also suppressed sphere formation, self-renewal capacity, and aldehyde dehydrogenase 1 (ALDH1) activity. In sphere-forming melanoma cells, TF3 downregulated key cancer stemness and drug resistance markers, including ABCB1, ABCG2, CD44, and CXCR4. Notably, TF3 reversed IGF-1-induced sphere formation, invasion, and MMP-9 expression. Mechanistically, TF3 suppressed IGF-1-mediated phosphorylation of focal adhesion kinase (FAK) and Src. In vivo, TF3 significantly inhibited tumor growth, reduced angiogenic marker expression, and suppressed lung metastasis. Collectively, these findings demonstrate that TF3 impedes melanoma progression by inhibiting metastasis and suppressing IGF-1-induced cancer stemness and invasiveness.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111751"},"PeriodicalIF":5.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obeticholic acid exacerbates liver injury through hepatocyte-mediated release of HMGB1 by inducing lysosomal membrane permeabilization in cholestasis","authors":"Jie Wang ,&nbsp;Qianhui Tang ,&nbsp;Zihang Yuan ,&nbsp;Haoran Zhang ,&nbsp;Yingying Miao ,&nbsp;Qingyu Chen ,&nbsp;Weishuang Shen ,&nbsp;Qinwei Yu ,&nbsp;Luyong Zhang ,&nbsp;Zhenzhou Jiang","doi":"10.1016/j.cbi.2025.111752","DOIUrl":"10.1016/j.cbi.2025.111752","url":null,"abstract":"<div><div>Obeticholic acid (OCA), a therapy for primary biliary cholangitis (PBC) unresponsive to ursodeoxycholic acid (UDCA), poses risks of hepatotoxicity that may worsen liver failure and increase mortality. Safety studies regarding OCA are imperative for guiding clinical practice. High-mobility group box 1 (HMGB1), an extracellular damage-associated molecular pattern molecule implicated in various liver pathologies, was mechanistically examined in the context of OCA-induced liver injury. In bile duct ligation (BDL) mice, OCA (40 mg/kg) administration significantly elevated serum and cytoplasmic levels of HMGB1, correlating with an exacerbated ductular reaction, necrosis, and liver fibrosis. Pharmacological inhibition of HMGB1 using ethyl pyruvate alleviated these pathological features. In vitro, OCA (100 μM) stimulated the release of HMGB1 (∼100 pg/mL) from primary hepatocyte supernatants. Mechanistic studies revealed that OCA-induced lysosomal membrane permeabilization triggered the leakage of cytosolic acid proteases, which prevented the autophagic degradation of cytoplasmic HMGB1 and promoted its subsequent extracellular release. These findings demonstrate that OCA-induced hepatocyte cell death occurs through lysosomal membrane permeabilization, which subsequently leads to the release of HMGB1. This highlights HMGB1 or lysosomal function as potential therapeutic targets for mitigating OCA-associated hepatotoxicity.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111752"},"PeriodicalIF":5.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding of Sunset Yellow, a food coloring, to human carbonic anhydrase II: Structural and functional insights from a multi-spectroscopic study","authors":"Faezeh Hasrati ,&nbsp;Sirous Ghobadi ,&nbsp;Zohreh Shariati","doi":"10.1016/j.cbi.2025.111746","DOIUrl":"10.1016/j.cbi.2025.111746","url":null,"abstract":"<div><div>The interaction of sunset yellow (SY), a widely used food coloring, with human carbonic anhydrase II (hCA II) was investigated using multiple spectroscopic techniques, including fluorescence, UV–Vis, and circular dichroism. The results showed that SY binds to hCA II, causing measurable changes in its enzymatic activity and structural properties. Fluorescence analyses indicated a quenching mechanism, while circular dichroism revealed alterations in secondary and tertiary structures. Moreover, SY binding affected the protein surface hydrophobicity index and its thermodynamic stability as well. Overall, these findings highlight that SY can modulate the structure and function of hCA II, providing insights with potential relevance to toxicology and enzymology.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111746"},"PeriodicalIF":5.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into male reproductive toxicity: autophagy-dependent ferroptosis triggered by polylactic acid nanoplastics and copper sulfate","authors":"Tiantian Jia ,&nbsp;Penghui Nie ,&nbsp;Yudeng Wang ,&nbsp;Hengyi Xu","doi":"10.1016/j.cbi.2025.111740","DOIUrl":"10.1016/j.cbi.2025.111740","url":null,"abstract":"<div><div>Polylactic acid (PLA) plastics are widely used in packaging for their safety and biocompatibility. However, PLA can generate micro/nanoplastics (MNPs), which infiltrate the food chain and pose health risks by adsorbing heavy metals such as copper (Cu) from the natural environment. This study investigated the role of autophagy-dependent ferroptosis in PLA NPs and Cu-induced testicular injury. C57BL/6J mice were orally exposed to 100 nm PLA NPs and copper sulfate (CuSO₄) for 4 weeks. The combined exposure caused significant reproductive toxicity, including reduced sperm counts and motility, increased sperm deformation, damaged blood-testis barrier, and disrupted sex hormone levels. Mechanistically, PLA NPs and CuSO₄ triggered oxidative stress and ferritinophagy, leading to iron overload and ferroptosis in testicular tissue. The critical involvement of this pathway was confirmed using ferroptosis and autophagy inhibitors, which mitigated testicular injury. These findings provide the first evidence of reproductive toxicity induced by bio-based PLA NPs and Cu co-exposure, highlighting the vital role of autophagy-dependent ferroptosis in testicular injury and offering new insights into the combined toxicological effects of nanoparticles and environmental pollutants.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111740"},"PeriodicalIF":5.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement and evaluation of vardenafil hydrochloride trihydrate absorption in orodispersible tablet formulations: Establishment of in vitro, in vivo correlation and bioequivalence study","authors":"Kok Zheng Gan ,&nbsp;Riyanto Teguh Widodo ,&nbsp;Zamri Chik ,&nbsp;Muhammad Luqman Nordin ,&nbsp;Liew Kai Bin","doi":"10.1016/j.cbi.2025.111745","DOIUrl":"10.1016/j.cbi.2025.111745","url":null,"abstract":"<div><div>The study's objectives were to create, produce, and test vardenafil hydrochloride trihydrate orodispersible tablets <em>in vitro</em> and to see how well they worked in rabbits. The absolute bioavailability of vardenafil hydrochloride trihydrate, a very strong and specific phosphodiesterase 5 (PDE5) inhibitor, is 15 %. Three different techniques were used to manufacture the orodispersible tablets: sublimation, effervescence, and superdisintegrant. Thickness, hardness, weight variation, friability, wetting time, <em>in vitro</em> disintegration time, and <em>in vitro</em> drug release were among the parameters that were evaluated for these formulations. Twelve New Zealand white rabbits participated in a randomized, single-dose, balanced, two-period crossover study to examine the pharmacokinetics. The modified formulation showed no signs of drug-excipient incompatibility, a reasonable tablet hardness (2.6 ± 0.15 kg/cm²), and a considerably improved disintegration time of 7.3 ± 1.1 s (p &lt; 0.05). The area under the curve (AUC₀-∞) for the test and reference formulations was 174.38 ± 95.91 and 176.45 ± 76.88, respectively, according to <em>in vivo</em> pharmacokinetic study. In comparison to the reference, the optimized formulation also showed better maximum concentration (Cmax) and a shorter time to achieve maximum concentration (Tmax). Overall, the optimized vardenafil orodispersible tablet showed improved peak concentration, quicker absorption, and comparable bioavailability to the reference formulation.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111745"},"PeriodicalIF":5.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of rubber pollutants 6PPD and 6PDQ on a complex membrane","authors":"José Villalaín","doi":"10.1016/j.cbi.2025.111739","DOIUrl":"10.1016/j.cbi.2025.111739","url":null,"abstract":"<div><div>Rubber products have been widely used with the development of industrial production, and hundreds of thousands of tons of the antioxidant and antiozonant molecule 6PPD has been widely used in their manufacture. The reaction of 6PPD with oxygen or ozone produces 6PDQ, and both 6PPD and 6PDQ has been shown to be toxic to living organisms. 6PPD and 6PDQ are hydrophobic and could insert into the biological membrane, and therefore able of affecting membrane structure and lipid components. I employed molecular dynamics to attain the behaviour of 6PPD and 6PDQ in a complex biomembrane. Both 6PPD and 6PDQ spontaneously insert into the membrane and can reside at different membrane depths, always in the monomeric state. 6PDQ, in some instances, attach to the membrane surface and move into the membrane, whereas in other instances insert into the membrane surface and leave it again at later times, without inserting into the membrane. 6PPD and 6PDQ insert between the phospholipids, increasing their fluidity. 6PPD and 6PDQ avoid PSM or CHOL and do not form hydrogen bonds with lipids, indicating that their displacement inside the membrane is not constrained by any form of interaction. Therefore, 6PPD and 6PDQ spontaneously insert into the biological membrane, affecting its physico-chemical properties. The insertion of 6PPD and 6PDQ into the biological membrane might be responsible for some of their harmful effects on living organisms.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111739"},"PeriodicalIF":5.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive characterisation of poly(ADPribosyl)ation in spermatozoa as a novel and early biomarker of sperm health. A preliminary look","authors":"Bruno Berman ,&nbsp;Gennaro Lettieri ,&nbsp;Martina Falace ,&nbsp;Carmela Marinaro ,&nbsp;Carmen Di Giovanni ,&nbsp;Anna Rita Bianchi ,&nbsp;Luigi Montano ,&nbsp;Marina Piscopo ,&nbsp;Anna De Maio","doi":"10.1016/j.cbi.2025.111747","DOIUrl":"10.1016/j.cbi.2025.111747","url":null,"abstract":"<div><div>Poly(ADPribose) polymerases (PARPs) are a family of enzymes involved in various biological processes, including DNA repair, maintaining genomic stability, chromatin compaction and cell death induction. PARP activation has been associated with oxidative stress (OS), which causes oxidative DNA damage and negatively affects sperm quality and function. OS plays a fundamental role in the aetiology of male infertility. As nuclear poly(ADPribose) polymerases (PARPs) are markers of DNA damage and their homologues have been found in testicular germ cells, this preliminary study examined the poly(ADPribosyl)ation system in the sperm of men living in the Sele River Valley (an area with low environmental exposure) and in the Land of Fires (an area sadly renowned for its high pollution levels). Additionally, the poly(ADPribosyl)ation of sperm nuclear basic proteins (SNBPs) was investigated for the first time, given that these proteins play a key role in the compaction of sperm chromatin. Our results revealed the presence of a complete and active poly(ADPribosyl)ation system and showed that PARP automodification is linked to the extent of sperm DNA damage. We have also demonstrated the endogenous SNBP heteromodification, which is associated with chromatin decondensation. Finally, we propose a molecular mechanism linking PARP automodification and DNA damage with SNBP heteromodification and the state of DNA compaction.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111747"},"PeriodicalIF":5.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing EPR spectroscopy with BMPO for UVA-induced radical detection in skin: Refining spin trapping and uncovering glutathione-dependent oxidative mechanisms","authors":"Shambhavi S. Ranade,&nbsp;Daniela F. Zamudio Díaz,&nbsp;Martina C. Meinke,&nbsp;Silke B. Lohan","doi":"10.1016/j.cbi.2025.111744","DOIUrl":"10.1016/j.cbi.2025.111744","url":null,"abstract":"<div><div>Ultraviolet A (UVA) irradiation significantly impacts skin health by generating free radicals, including reactive oxygen species (ROS), lipid oxygen species (LOS), and carbon-centered radicals (CCR), contributing to oxidative stress. Electron paramagnetic resonance (EPR) spectroscopy enables the direct detection of these radicals, using spin traps like 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO). While DMPO is suitable for detecting short-lived species such as hydroxy (•OH) and alkoxy radicals, BMPO offers greater stability, particularly for superoxide (O₂⁻) and hydroperoxyl radicals (•OOH).</div><div>This study refines EPR-based protocols for radical detection in UVA-irradiated skin by comparing DMPO and BMPO, revealing a shift from short-lived ROS to more stable LOS with increasing UVA-exposure. For the first time, the glutathione (GSH)-mediated conversion of O₂⁻ to •OH was directly quantified via spin trapping in skin tissue. Although GSH functions as a central antioxidant in skin, it indirectly promotes •OH formation via the Fenton reaction under UV-induced oxidative stress, potentially contributing to tissue damage. BMPO's enhanced stability as a spin trap for O₂⁻ in skin tissue enables precise detection of this GSH-dependent radical transformation, offering new insights into protective and damaging mechanisms under oxidative conditions. A standardized protocol for ex situ UVA irradiation of skin and subsequent radical measurement was developed, establishing a foundation for future studies with other stress factors.</div><div>This research refines spin trapping methodologies and advances the understanding of UVA-induced oxidative processes, offering a framework for future dermatological and photobiological investigations.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"421 ","pages":"Article 111744"},"PeriodicalIF":5.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}