{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:43:50Z","timestamp":1760240630519,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T00:00:00Z","timestamp":1565395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology","award":["UID\/AGR\/04033\/2019, UID\/EQU\/00511\/2019; UID\/CVT\/00772\/2019; LEPABE-2-ECO-INNOVATION\u201d \u2013 NORTE\u201001\u20100145\u2010FEDER\u2010000005 and PEst-OE\/QUI\/UI0616\/2014"],"award-info":[{"award-number":["UID\/AGR\/04033\/2019, UID\/EQU\/00511\/2019; UID\/CVT\/00772\/2019; LEPABE-2-ECO-INNOVATION\u201d \u2013 NORTE\u201001\u20100145\u2010FEDER\u2010000005 and PEst-OE\/QUI\/UI0616\/2014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant efficacy, but also considerable toxicity. This study addresses the chemopreventive effect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16\u2212\/\u2212, n = 10, parecoxib-treated); II (HPV16\u2212\/\u2212 n = 11, untreated); III (HPV16+\/\u2212, n = 11, parecoxib-treated) and IV (HPV16+\/\u2212, n = 11, untreated). Parecoxib (5.0 mg\/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+\/\u2212 treated animals (0% versus 64% in HPV16+\/\u2212 untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+\/\u2212 treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn\u2019t modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive effects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.<\/jats:p>","DOI":"10.3390\/ijms20163902","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T06:38:02Z","timestamp":1565591882000},"page":"3902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Cyclooxigenase-2 Inhibitor Parecoxib Prevents Epidermal Dysplasia in HPV16-Transgenic Mice: Efficacy and Safety Observations"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-9770","authenticated-orcid":false,"given":"Tiago","family":"Ferreira","sequence":"first","affiliation":[{"name":"Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"given":"Sandra","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"given":"M\u00f3nica G.","family":"Silva","sequence":"additional","affiliation":[{"name":"CQVR, Chemistry Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"given":"Rita","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"CQVR, Chemistry Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"given":"Susana","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"given":"Jos\u00e9","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-2449","authenticated-orcid":false,"given":"Rui Miguel","family":"Gil da Costa","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"},{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy, (LEPABE) Chemical Engineering Department, Faculty of Engineering, University of Porto (FEUP), 4000 Porto, Portugal"},{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), 4000 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2108-2629","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"C\u00f3rdova","sequence":"additional","affiliation":[{"name":"School of Health Dr. Lopes Dias, IPC, 6000 Castelo Branco, Portugal"}]},{"given":"Ant\u00f3nio","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Mountain Research Centre (CIMO), IPB, 5300 Bragan\u00e7a, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Neuparth","sequence":"additional","affiliation":[{"name":"Advanced Polytechnic and University Cooperative (CESPU), Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), 4585 Gandra, Portugal"},{"name":"Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto, 4000 Porto, Portugal"}]},{"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), 4000 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), 4000 Porto, Portugal"},{"name":"CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, 4000 Porto, Portugal"},{"name":"LPCC Research Department, Portuguese League against Cancer (NRNorte), 4000 Porto, Portugal"}]},{"given":"Margarida Maria da Silva","family":"Monteiro Bastos","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), 4000 Porto, Portugal"}]},{"given":"Isabel","family":"Gaiv\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Genetics and Biotechnology and Animal and Veterinary Research Centre (CECAV), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-7477","authenticated-orcid":false,"given":"Francisco","family":"Peixoto","sequence":"additional","affiliation":[{"name":"CQVR, Biology and Environment Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"given":"Maria Manuel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CQVR, Chemistry Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4044","authenticated-orcid":false,"given":"Paula Alexandra","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/omi.2018.0065","article-title":"How Does Infection with Human Papillomavirus 16 and 18 Impact on DNA Damage and Repair in Cervical Cells and Peripheral Blood?","volume":"22","author":"Ozcagli","year":"2018","journal-title":"OMICS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.virol.2008.10.004","article-title":"Interaction of Human Papillomaviruses with the Host Immune System: A Well Evolved Relationship","volume":"384","author":"Frazer","year":"2009","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2016.86","article-title":"Carcinogenic Human Papillomavirus Infection","volume":"2","author":"Schiffman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00423-006-0073-1","article-title":"Chronic Inflammation and Oxidative Stress in the Genesis and Perpetuation of Cancer: Role of Lipid Peroxidation, DNA Damage, and Repair","volume":"391","author":"Bartsch","year":"2006","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.virusres.2018.01.003","article-title":"Cellular Redox, Cancer and Human Papillomavirus","volume":"246","author":"Lizano","year":"2018","journal-title":"Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1067\/moe.2001.115392","article-title":"Human Papillomavirus as a Risk Factor for Oral Squamous Cell Carcinoma: A Meta-Analysis, 1982\u20131997","volume":"91","author":"Miller","year":"2001","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1056\/NEJM200104123441503","article-title":"Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and Neck","volume":"344","author":"Mork","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S1470-2045(14)70471-1","article-title":"HPV DNA, E6\/E7 MRNA, and P16INK4a Detection in Head and Neck Cancers: A Systematic Review and Meta-Analysis","volume":"15","author":"Ndiaye","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ccr.2009.12.019","article-title":"FcRgamma Activation Regulates Inflammation-Associated Squamous Carcinogenesis","volume":"17","author":"Andreu","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1002\/1097-0142(20001215)89:12<2637::AID-CNCR17>3.0.CO;2-B","article-title":"COX-2 Is Expressed in Human Pulmonary, Colonic, and Mammary Tumors","volume":"89","author":"Soslow","year":"2000","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.3008455","article-title":"COX-2 Inhibition Potentiates Antiangiogenic Cancer Therapy and Prevents Metastasis in Preclinical Models","volume":"6","author":"Xu","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/2048731","article-title":"Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy","volume":"2016","author":"Pang","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_13","first-page":"82","article-title":"Differential Usage of COX-1 and COX-2 in Prostaglandin Production by Mast Cells and Basophils","volume":"10","author":"Bando","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.lfs.2016.05.040","article-title":"Celecoxib Promotes Degranulation of CD8 + T Cells in HPV-Induced Lesions of K14-HPV16 Transgenic Mice","volume":"157","author":"Santos","year":"2016","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejphar.2004.03.013","article-title":"Pharmacological Profile of Parecoxib: A Novel, Potent Injectable Selective Cyclooxygenase-2 Inhibitor","volume":"491","author":"Padi","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jpba.2018.05.034","article-title":"Simultaneous Determination of Parecoxib and Its Main Metabolites Valdecoxib and Hydroxylated Valdecoxib in Mouse Plasma with a Sensitive LC\u2013MS\/MS Method to Elucidate the Decreased Drug Metabolism of Tumor Bearing Mice","volume":"158","author":"Jin","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_17","unstructured":"Education, M.H. (2011). Lipid-Derived Autacoids: Eicosanoids and Platelet-Activating Factor. Goodman & Gilman\u2019s\u2014The Pharmacological Basis of Therapeutics, McGraw-Hill Education. [12th ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"627","DOI":"10.7314\/APJCP.2015.16.2.627","article-title":"Parecoxib: An Enhancer of Radiation Therapy for Colorectal Cancer","volume":"16","author":"Xiong","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3892\/ol.2015.2884","article-title":"Link between Chronic Inflammation and Human Papillomavirus-Induced Carcinogenesis (Review)","volume":"9","author":"Fernandes","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_20","first-page":"1461","article-title":"Curcumin and Rutin Down-Regulate Cyclooxygenase-2 and Reduce Tumor-Associated Inflammation in HPV16-Transgenic Mice","volume":"38","author":"Moutinho","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.2165\/00003495-200464230-00001","article-title":"NSAID-Related Psychiatric Adverse Events: Who Is at Risk?","volume":"64","author":"Onder","year":"2004","journal-title":"Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ageing\/afs199","article-title":"Guidance on the Management of Pain in Older People","volume":"42","author":"Abdulla","year":"2013","journal-title":"Age Ageing"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Veettil, S.K., Lim, K.G., Ching, S.M., Saokaew, S., and Phisalprapa, P. (2017). Effects of Aspirin and Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs on the Incidence of Recurrent Colorectal Adenomas: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3757-8"},{"key":"ref_24","first-page":"1","article-title":"Non-Steroidal Anti-Inflammatory Agents to Induce Regression and Prevent the Progression of Cervical Intraepithelial Neoplasia (Review)","volume":"9","author":"Grabosch","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1128\/jvi.68.7.4358-4368.1994","article-title":"Progressive Squamous Epithelial Neoplasia in K14-Human Papillomavirus Type 16 Transgenic Mice","volume":"68","author":"Arbeit","year":"1994","journal-title":"J. Virol."},{"key":"ref_26","first-page":"1899","article-title":"Genetic Predisposition and Parameters of Malignant Progression in K14- HPV16 Transgenic Mice","volume":"149","author":"Coussens","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1128\/jvi.70.3.1873-1881.1996","article-title":"Squamous Epithelial Hyperplasia and Carcinoma in Mice Transgenic for the Human Papillomavirus Type 16 E7 Oncogene","volume":"70","author":"Herber","year":"1996","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.lfs.2016.10.031","article-title":"HPV16 Induces a Wasting Syndrome in Transgenic Mice: Amelioration by Dietary Polyphenols via NF-\u039aB Inhibition","volume":"169","author":"Moutinho","year":"2017","journal-title":"Life Sci."},{"key":"ref_29","first-page":"227","article-title":"Cyclooxygenase-2 Inhibition Attenuates Surgically Induced Residual Tumour Growth and Metatases Following Cytoreductive Surgery in a Murine Model of Breast Cancer","volume":"114","author":"Harmey","year":"2003","journal-title":"J. Surg. Res."},{"key":"ref_30","first-page":"527","article-title":"Cyclooxygenase Inhibitors Decrease the Growth and Induce Regression of Human Esophageal Adenocarcinoma Xenografts in Nude Mice","volume":"40","author":"Santander","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1158\/1078-0432.41.11.1","article-title":"Cyclooxygenase-2 Is a Target of KRAS D12, Which Facilitates the Outgrowth of Murine C26 Colorectal Liver Metastases","volume":"11","author":"Smakman","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1007\/s00262-011-1196-y","article-title":"Inhibition of Cyclooxygenase-2 Enhances Immunotherapy against Experimental Brain","volume":"61","author":"Badn","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6868","DOI":"10.1002\/jcb.28007","article-title":"Oxidative Stress in Cervical Cancer Pathogenesis and Resistance to Therapy","volume":"120","author":"Ebrahimi","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_34","first-page":"58","article-title":"Inflammation and Cancer","volume":"90","author":"Coussens","year":"2012","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00280-009-1031-8","article-title":"Celecoxib Prevents Tumor Growth in an Animal Model by a COX-2 Independent Mechanism","volume":"65","author":"Lugarini","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.lfs.2015.02.020","article-title":"MicroRNA-21 Expression and Susceptibility to HPV-Induced Carcinogenesis\u2014Role of Microenvironment in K14-HPV16 Mice Model","volume":"128","author":"Paiva","year":"2015","journal-title":"Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Paiva, I., Gil da Costa, R.M., Ribeiro, J., Sousa, H., Bastos, M., Faustino-Rocha, A., Oliveira, P.A., and Medeiros, R. (2015). A Role for MicroRNA-155 Expression in Microenvironment Associated to HPV-Induced Carcinogenesis in K14-HPV16 Transgenic Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116868"},{"key":"ref_38","unstructured":"Forbes, D., Blom, H., Kostomitsopulos, N., Moore, G., and Perretta, G. (2007). Euroguide: On the Accommodation and Care of Animals Used for Experimental and Other Scientific Purposes, Federation of European Laboratory Animal Science Associations."},{"key":"ref_39","first-page":"1073","article-title":"Implementation of Human Endpoints in a Urinary Bladder Carcinogenesis Study in Rats","volume":"31","author":"Oliveira","year":"2017","journal-title":"In Vivo"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1385\/MB:26:3:249","article-title":"The Comet Assay for DNA Damage and Repair","volume":"26","author":"Collins","year":"2004","journal-title":"Mol. Biotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.toxlet.2010.02.017","article-title":"Twelve-Gel Slide Format Optimised for Comet Assay and Fluorescent in Situ Hybridisation","volume":"195","author":"Shaposhnikov","year":"2010","journal-title":"Toxicol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.mrgentox.2008.10.013","article-title":"DNA Oxidation: Investigating Its Key Role in Environmental Mutagenesis with the Comet Assay","volume":"674","author":"Azqueta","year":"2009","journal-title":"Mutat. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S0021-9258(18)57021-6","article-title":"Determination of Serum Proteins by Means of the Biuret Reaction","volume":"177","author":"Gornall","year":"1949","journal-title":"J. Biol. Chem."},{"key":"ref_44","first-page":"205","article-title":"Interactions of a Series of Coumarins with Reactive Oxygen Species","volume":"44","author":"Halliwell","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.pestbp.2005.10.007","article-title":"Toxicological Effects of Oxyfluorfen on Oxidative Stress Enzymes in Tilapia Oreochromis Niloticus","volume":"85","author":"Peixoto","year":"2006","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/jat.1763","article-title":"Mitochondrial and Liver Oxidative Stress Alterations Induced by N-Butyl-N-(4-Hydroxybutyl)Nitrosamine: Relevance for Hepatotoxicity","volume":"33","author":"Oliveira","year":"2013","journal-title":"J. Appl. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2174\/1567205012666150204124852","article-title":"Age-Dependent Biochemical Dysfunction in Skeletal Muscle of Triple- Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"12","author":"Castro","year":"2015","journal-title":"Curr. Alzheimer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejphar.2017.03.044","article-title":"Propofol Affinity to Mitochondrial Membranes Does Not Alter Mitochondrial Function","volume":"803","author":"Correia","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/(SICI)1096-9063(199603)46:3<267::AID-PS347>3.0.CO;2-N","article-title":"Glutathione Transferase Activities and Herbicide Selectivity in Maize and Associated Weed Species","volume":"46","author":"Hatton","year":"1996","journal-title":"Pestic. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1038\/sj.eye.6702596","article-title":"Evidence for Oxidative Stress in Lens Epithelial Cells in Pseudoexfoliation Syndrome","volume":"21","author":"Gartaganis","year":"2007","journal-title":"Eye"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/0003-2697(76)90326-2","article-title":"A Fluorometric Method for Determination of Oxidized and Reduced Glutathione in Tissues","volume":"74","author":"Hissin","year":"1976","journal-title":"Anal. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/3902\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:10:09Z","timestamp":1760188209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/3902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,10]]},"references-count":51,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20163902"],"URL":"https:\/\/doi.org\/10.3390\/ijms20163902","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2019,8,10]]}}}