{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T08:20:35Z","timestamp":1786782035375,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ongoing Research Program, King Saud University, Riyadh, Saudi Arabia","award":["ORF-2025-575"],"award-info":[{"award-number":["ORF-2025-575"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Cisplatin is a powerful treatment for cancer; however, its clinical application is compromised due to its potential for nephrotoxicity. The development of nephroprotective agents is hindered mainly due to the lack of understanding of the exact underlying mechanism. Additionally, the identification of safe nephroprotective agents that can be used as an adjunct to cisplatin is necessary. Methods: Rats were pretreated with thymol (60 mg\/kg, orally) daily for two weeks and received a single cisplatin injection (8 mg\/kg, i.p.) on the seventh day to induce nephrotoxicity. Results: Thymol prevented cisplatin-induced renal injury and restored serum creatinine and blood urea nitrogen. The renoprotective activity of thymol was further validated by histopathological studies, as demonstrated by the preserved architectures of the glomeruli, proximal, and distal convoluted tubules. Oxidative stress plays an important role in the pathophysiology of nephrotoxicity. Herein, cisplatin administration increased lipid peroxides and depleted the cellular antioxidant defense mechanisms (GSH, SOD, Nrf2, and HO-1). Interestingly, thymol remarkably ameliorated these alterations and restored oxidative status. We further examined the impact of cisplatin and\/or thymol on cuproptosis, a distinct type of cell death associated with the excess intracellular accumulation of copper which is aggravated by oxidative stress. Pretreatment with thymol blunted the cisplatin-induced upregulation of genes associated with cuproptosis, including SLC31A1, DLAT, FDX1, LIAS, and ATP7A, as well as FDX1 protein expression. Furthermore, the molecular docking studies of thymol demonstrated favorable fitting and interactions with the conservative amino acids of FDX-1, DLAT, and ATP7A. This further supports the inhibitory effect of thymol on cuproptosis, which underlies its protective properties. Conclusions: This study illustrates that cuproptosis and oxidative stress play crucial roles in the development and progression of cisplatin-induced nephrotoxicity, and the protective activity of thymol is attributed, at least in part, to blunting these mechanisms.<\/jats:p>","DOI":"10.3390\/ph18111686","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T10:56:45Z","timestamp":1762513005000},"page":"1686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cuproptosis Contributes to Cisplatin-Induced Nephrotoxicity: Insights into Thymol\u2019s Potential Inhibitory and Protective Effects"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-771X","authenticated-orcid":false,"given":"Layla A.","family":"Al-Kharashi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-868X","authenticated-orcid":false,"given":"Amira M.","family":"Badr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem T.","family":"Atawia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Southwestern Oklahoma State University, Weatherford, OK 73096, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-5040","authenticated-orcid":false,"given":"Elshaymaa I.","family":"Elmongy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-8963","authenticated-orcid":false,"given":"Hanan","family":"Henidi","sequence":"additional","affiliation":[{"name":"Research Department, Natural and Health Sciences Research Center, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab","family":"Ali","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awatif A.","family":"Binmughram","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Al-Abkka","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4285-9097","authenticated-orcid":false,"given":"Nervana Mostafa Kamal","family":"Bayoumy","sequence":"additional","affiliation":[{"name":"Physiology Department, College of Medicine, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6306-5616","authenticated-orcid":false,"given":"Yasmen F.","family":"Mahran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1200\/JOP.2011.000394","article-title":"Benchmarks for value in cancer care: An analysis of a large commercial population","volume":"7","author":"Kolodziej","year":"2011","journal-title":"J. Oncol. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.lfs.2004.11.005","article-title":"Naringenin attenuates cisplatin nephrotoxicity in rats","volume":"76","author":"Badary","year":"2005","journal-title":"Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ctrv.2006.09.006","article-title":"Molecular mechanisms of resistance and toxicity associated with platinating agents","volume":"33","author":"Rabik","year":"2007","journal-title":"Cancer Treat. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1039\/C0MT00058B","article-title":"Comparative hydrolysis and plasma protein binding of cis-platin and carboplatin in human plasma in vitro","volume":"3","author":"Sooriyaarachchi","year":"2011","journal-title":"Metallomics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/sj.bmt.1700980","article-title":"Nephrotoxicity after high-dose carboplatin, etoposide and ifosfamide in germ-cell tumors: Incidence and implications for hematologic recovery and clinical outcome","volume":"20","author":"Beyer","year":"1997","journal-title":"Bone Marrow Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/sj.ki.5002786","article-title":"Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies","volume":"73","author":"Pabla","year":"2008","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/S0959-8049(98)00224-X","article-title":"Clinical development of platinum complexes in cancer therapy: An historical perspective and an update","volume":"34","author":"Lebwohl","year":"1998","journal-title":"Eur. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.2215\/CJN.03140312","article-title":"Onco-nephrology: AKI in the cancer patient","volume":"7","author":"Lam","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/s41423-022-00866-1","article-title":"Cuproptosis: A new form of programmed cell death","volume":"19","author":"Wang","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"jcs240523","DOI":"10.1242\/jcs.240523","article-title":"Dynamic and cell-specific transport networks for intracellular copper ions","volume":"134","author":"Lutsenko","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s13046-023-02720-2","article-title":"Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer","volume":"42","author":"Wang","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41422-022-00653-7","article-title":"Cuproptosis: A copper-triggered modality of mitochondrial cell death","volume":"32","author":"Tang","year":"2022","journal-title":"Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.bbamcr.2015.01.018","article-title":"Emerging critical roles of Fe\u2013S clusters in DNA replication and repair","volume":"1853","author":"Fuss","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Springer, C., Humayun, D., and Skouta, R. (2024). Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy. Cancers, 16.","DOI":"10.3390\/cancers16030647"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Qiu, Z., Liu, Q., Wang, L., Xiong, Y., Wu, J., Wang, M., Yan, X., and Deng, H. (2024). The copper transporter, SLC31A1, transcriptionally activated by ELF3, imbalances copper homeostasis to exacerbate cisplatin-induced acute kidney injury through mitochondrial dysfunction. Chem.-Biol. Interact., 393.","DOI":"10.1016\/j.cbi.2024.110943"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30662","DOI":"10.1039\/D4RA03941F","article-title":"Thymol and carvacrol derivatives as anticancer agents; synthesis, in vitro activity, and computational analysis of biological targets","volume":"14","author":"Alamri","year":"2024","journal-title":"RSC Adv."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mahran, Y.F., Badr, A.M., Al-Kharashi, L.A., Alajami, H.N., Aldamry, N.T., Bayoumy, N.M., Elmongy, E.I., and Soliman, S. (2024). Thymol Protects against 5-Fluorouracil-Induced Hepatotoxicity via the Regulation of the Akt\/GSK-3\u03b2 Pathway in In Vivo and In Silico Experimental Models. Pharmaceuticals, 17.","DOI":"10.3390\/ph17081094"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yin, L., Liang, C., Wei, W., Huang, S., Ren, Y., Geng, Y., Huang, X., Chen, D., Guo, H., and Fang, J. (2022). The antibacterial activity of thymol against drug-resistant Streptococcus iniae and its protective effect on channel catfish (Ictalurus punctatus). Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.914868"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2015.11.033","article-title":"Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL\/6J mice","volume":"245","author":"Saravanan","year":"2016","journal-title":"Chem.-Biol. Interact."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1055\/a-0646-3803","article-title":"In vivo evaluation of anti-hyperglycemic, anti-hyperlipidemic and anti-oxidant status of liver and kidney of thymol in STZ-induced diabetic rats","volume":"69","author":"Oskouei","year":"2019","journal-title":"Drug Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mahran, Y.F., Al-Kharashi, L.A., Atawia, R.T., Alanazi, R.T., Dhahi, A.M.B., Alsubaie, R., and Badr, A.M. (2023). Radioprotective effects of Carvacrol and\/or Thymol against Gamma irradiation-induced acute nephropathy: In silico and in vivo evidence of the involvement of insulin-like growth factor-1 (IGF-1) and calcitonin gene-related peptide. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092521"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/jbt.21681","article-title":"Thymol and carvacrol prevent cisplatin-induced nephrotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats","volume":"29","author":"Mansour","year":"2015","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41589-019-0291-9","article-title":"Mitochondrial metabolism promotes adaptation to proteotoxic stress","volume":"15","author":"Tsvetkov","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/j.molcel.2022.05.001","article-title":"Cuproptosis: Cellular and molecular mechanisms underlying copper-induced cell death","volume":"82","author":"Cobine","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s00204-012-0821-7","article-title":"Cisplatin-induced nephrotoxicity and targets of nephroprotection: An update","volume":"86","author":"Martins","year":"2012","journal-title":"Arch. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1517\/14740338.2.6.597","article-title":"Toxicities of the platinum antineoplastic agents","volume":"2","author":"Markman","year":"2003","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1248\/bpb.28.1385","article-title":"Relationship between cisplatin or nedaplatin-induced nephrotoxicity and renal accumulation","volume":"28","author":"Kawai","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_29","first-page":"1663","article-title":"Cisplatin and platinum drugs at the molecular level","volume":"10","author":"Boulikas","year":"2003","journal-title":"Oncol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"99","DOI":"10.4212\/cjhp.v70i2.1641","article-title":"Risk factors for nephrotoxicity associated with cisplatin","volume":"70","author":"Almanric","year":"2017","journal-title":"Can. J. Hosp. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2227728","DOI":"10.1080\/0886022X.2023.2227728","article-title":"Protective effect of thymol on glycerol-induced acute kidney injury","volume":"45","author":"Wang","year":"2023","journal-title":"Ren. Fail."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.freeradbiomed.2024.09.049","article-title":"Cisplatin induces kidney damage through the down-regulation of Prx I by autophagic degradation","volume":"225","author":"Park","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1046\/j.1523-1755.1998.00767.x","article-title":"In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity","volume":"53","author":"Baliga","year":"1998","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1254\/jphs.FP0050661","article-title":"Relationship of intracellular calcium and oxygen radicals to cisplatin-related renal cell injury","volume":"100","author":"Kawai","year":"2006","journal-title":"J. Pharmacol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.intimp.2016.04.007","article-title":"Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity","volume":"36","author":"Chen","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1080\/1061186X.2024.2356736","article-title":"Targeting Nrf2 Signaling Pathway: New Therapeutic Strategy for Cardiovascular Diseases","volume":"32","author":"Wu","year":"2024","journal-title":"J. Drug Target."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8061","DOI":"10.2147\/JIR.S490418","article-title":"The NRF-2\/HO-1 signaling pathway: A promising therapeutic target for metabolic dysfunction-associated steatotic liver disease","volume":"17","author":"Li","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.biopha.2017.06.085","article-title":"Sinapic acid modulates Nrf2\/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats","volume":"93","author":"Ansari","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"112511","DOI":"10.1016\/j.intimp.2024.112511","article-title":"Piracetam mitigates nephrotoxicity induced by cisplatin via the AMPK-mediated PI3K\/Akt and MAPK\/JNK\/ERK signaling pathways","volume":"137","author":"Alzokaky","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Peirovy, Y., and Asle-Rousta, M. (2024). Thymol and p-Cymene Protect the Liver by Mitigating Oxidative Stress, Suppressing TNF-\u03b1\/NF-\u03ba B, and Enhancing Nrf2\/HO-1 Expression in Immobilized Rats. Chem. Biol. Drug Des., 104.","DOI":"10.1111\/cbdd.14618"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s11011-016-9921-z","article-title":"Thymol improves high-fat diet-induced cognitive deficits in mice via ameliorating brain insulin resistance and upregulating NRF2\/HO-1 pathway","volume":"32","author":"Fang","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Badr, A.M., Al-Kharashi, L.A., Attia, H., Alshehri, S., Alajami, H.N., Ali, R.A., and Mahran, Y.F. (2023). TLR4\/inflammasomes cross-talk and pyroptosis contribute to N-Acetyl cysteine and chlorogenic acid protection against cisplatin-induced nephrotoxicity. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030337"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1039\/C7MT00066A","article-title":"Cellular copper homeostasis: Current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases","volume":"9","author":"Bhattacharjee","year":"2017","journal-title":"Metallomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2212267","DOI":"10.1002\/adma.202212267","article-title":"Cuproptosis induced by ROS responsive nanoparticles with elesclomol and copper combined with \u03b1PD-L1 for enhanced cancer immunotherapy","volume":"35","author":"Guo","year":"2023","journal-title":"Adv. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.freeradbiomed.2025.01.029","article-title":"Merestinib inhibits cuproptosis by targeting NRF2 to alleviate acute liver injury","volume":"229","author":"Luo","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Liu, J., Tang, H., Chen, F., Li, C., Xie, Y., Kang, R., and Tang, D. (2024). NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-81317-x"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/s41419-024-07206-3","article-title":"Copper homeostasis and cuproptosis in central nervous system diseases","volume":"15","author":"Zhu","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41420-023-01796-1","article-title":"Copper homeostasis and cuproptosis in atherosclerosis: Metabolism, mechanisms and potential therapeutic strategies","volume":"10","author":"Yang","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2431142","DOI":"10.1080\/0886022X.2024.2431142","article-title":"Copper-instigated modulatory cell mortality mechanisms and progress in kidney diseases","volume":"47","author":"Ren","year":"2025","journal-title":"Ren. Fail."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"883","DOI":"10.2147\/JIR.S498340","article-title":"Cuproptosis Cell Death Molecular Events and Pathways to Liver Disease","volume":"18","author":"Mao","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41420-023-01564-1","article-title":"Ammonium tetrathiomolybdate relieves oxidative stress in cisplatin-induced acute kidney injury via NRF2 signaling pathway","volume":"9","author":"Qi","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1186\/s12964-024-01726-3","article-title":"The crosstalk between copper-induced oxidative stress and cuproptosis: A novel potential anticancer paradigm","volume":"22","author":"Vo","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/biof.2052","article-title":"SP1\/CTR1-mediated oxidative stress-induced cuproptosis in intervertebral disc degeneration","volume":"50","author":"Chen","year":"2024","journal-title":"Biofactors"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.cbpa.2010.01.003","article-title":"Human copper homeostasis: A network of interconnected pathways","volume":"14","author":"Lutsenko","year":"2010","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.bbamcr.2012.02.011","article-title":"Charting the travels of copper in eukaryotes from yeast to mammals","volume":"1823","author":"Nevitt","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1007\/s10495-024-02021-9","article-title":"Sirtuin 7 ameliorates cuproptosis, myocardial remodeling and heart dysfunction in hypertension through the modulation of YAP\/ATP7A signaling","volume":"29","author":"Chen","year":"2024","journal-title":"Apoptosis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1080\/15548627.2023.2200554","article-title":"Copper metabolism in cell death and autophagy","volume":"19","author":"Xue","year":"2023","journal-title":"Autophagy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0003-2697(78)90342-1","article-title":"Determination of malonaldehyde precursor in tissues by thiobarbituric acid test","volume":"86","author":"Uchiyama","year":"1978","journal-title":"Anal. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Butt, S.S., Badshah, Y., Shabbir, M., and Rafiq, M. (2020). Molecular docking using chimera and autodock vina software for nonbioinformaticians. JMIR Bioinform. Biotechnol., 1.","DOI":"10.2196\/14232"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Badr, M., Elmongy, E.I., Elkhateeb, D., Moemen, Y.S., Khalil, A., Ali, H., Binsuwaidan, R., Awadallah, F., and El Sayed, I.E.T. (2024). In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine\/Sulfonamide Hybrids Targeting Topoisomerases I and II. Pharmaceuticals, 17.","DOI":"10.3390\/ph17111487"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1686\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T11:14:28Z","timestamp":1762514068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":61,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ph18111686"],"URL":"https:\/\/doi.org\/10.3390\/ph18111686","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]}}}