{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:38:43Z","timestamp":1781804323819,"version":"3.54.5"},"reference-count":98,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100016177","name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Sistemas Complexos","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016177","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["406020\/2022\\u20131"],"award-info":[{"award-number":["406020\/2022\\u20131"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.bcp.2025.117622","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T16:00:46Z","timestamp":1765036846000},"page":"117622","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Sex\u2010specific mitigation of oxidative and inflammatory cardiac alterations by folic acid and simvastatin in chronic mild hyperhomocysteinemia"],"prefix":"10.1016","volume":"245","author":[{"given":"Gustavo Ricardo Krupp","family":"Prauchner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra Schmitt","family":"Rieder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Teixeira","family":"da Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Soares","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Scherer","family":"Louzada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto Bergozza","family":"Bonatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Camaratta","family":"Dossin Bastos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela T.S.","family":"Wyse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2025.117622_b0005","doi-asserted-by":"crossref","DOI":"10.3390\/biom11050737","article-title":"Homocysteine: Biochemistry, molecular biology and role in disease","volume":"11","author":"Hermann","year":"2021","journal-title":"Biomolecules"},{"key":"10.1016\/j.bcp.2025.117622_b0010","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.2174\/0929867325666180313105949","article-title":"Homocysteine and hyperhomocysteinaemia","volume":"26","author":"Zaric","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.bcp.2025.117622_b0015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms21207698","article-title":"Homocysteine and mitochondria in cardiovascular and cerebrovascular systems","volume":"21","author":"Kaplan","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bcp.2025.117622_b0020","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41430-021-00983-6","article-title":"Prevalence of hyperhomocysteinemia (HHcy) and its major determinants among hypertensive patients over 35 years of age","volume":"76","author":"Cheng","year":"2022","journal-title":"Eur. J. Clin. Nutr."},{"key":"10.1016\/j.bcp.2025.117622_b0025","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11883-004-0097-3","article-title":"Homocysteine and cardiovascular disease","volume":"6","author":"Kalra","year":"2004","journal-title":"Curr. Atheroscler. Rep."},{"key":"10.1016\/j.bcp.2025.117622_b0030","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.817579","article-title":"Estradiol and Hyperhomocysteinemia Are Linked Predominantly Through Part Renal Function Indicators","volume":"13","author":"Niu","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"10.1016\/j.bcp.2025.117622_b0035","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1001\/archinte.159.10.1077","article-title":"Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women","volume":"159","author":"Bostom","year":"1999","journal-title":"Arch. Intern. Med."},{"key":"10.1016\/j.bcp.2025.117622_b0040","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1146\/annurev-nutr-071715-050947","article-title":"Homocysteine, B Vitamins, and cognitive impairment","volume":"36","author":"Smith","year":"2016","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.bcp.2025.117622_b0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2024.111028","article-title":"Mild hyperhomocysteinemia alters oxidative stress profile via Nrf2, inflammation and cholinesterases in cardiovascular system of aged male rats","volume":"396","author":"Prauchner","year":"2024","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.bcp.2025.117622_b0050","doi-asserted-by":"crossref","first-page":"515","DOI":"10.33549\/physiolres.935280","article-title":"Hyperhomocysteinemia-induced alterations in protein expression and oxidative stress parameters in rat heart","volume":"73","author":"Tatarkov\u00e1","year":"2024","journal-title":"Physiol. Res."},{"key":"10.1016\/j.bcp.2025.117622_b0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2021.120111","article-title":"Nrf2\/Keap1\/ARE signaling: Towards specific regulation","volume":"291","author":"Ulasov","year":"2022","journal-title":"Life Sci."},{"key":"10.1016\/j.bcp.2025.117622_b0060","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.bcp.2025.117622_b0065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2013.08.011","article-title":"Downregulation of Nrf2\/HO-1 pathway and activation of JNK\/c-Jun pathway are involved in homocysteic acid-induced cytotoxicity in HT-22 cells","volume":"223","author":"Tan","year":"2013","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.bcp.2025.117622_b0070","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bbrc.2021.02.025","article-title":"Hyperhomocysteinemia-induced Nrf2\/HO-1 pathway suppression aggravates cardiac remodeling of hypertensive rats","volume":"547","author":"Cao","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.bcp.2025.117622_b0075","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.freeradbiomed.2015.05.036","article-title":"Oxidative stress response and Nrf2 signaling in aging","volume":"88","author":"Zhang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.bcp.2025.117622_b0080","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2022.101756","article-title":"Role of Nrf2 in aging, Alzheimer\u2019s and other neurodegenerative diseases","volume":"82","author":"George","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.bcp.2025.117622_b0085","article-title":"Folate reverses NF-\u03baB p65\/Rela\/IL-6 level induced by hyperhomocysteinemia in spontaneously hypertensive rats","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.bcp.2025.117622_b0090","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041197","article-title":"Aging and inflammation","volume":"14","author":"Singh","year":"2024","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.bcp.2025.117622_b0095","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1055\/s-0044-1788280","article-title":"Atherogenic effect of homocysteine, a biomarker of inflammation and its treatment","volume":"33","author":"Prasad","year":"2024","journal-title":"Int. J. Angiol."},{"key":"10.1016\/j.bcp.2025.117622_b0100","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.it.2022.07.004","article-title":"NF-\u03baB: blending metabolism, immunity, and inflammation","volume":"43","author":"Capece","year":"2022","journal-title":"Trends Immunol."},{"key":"10.1016\/j.bcp.2025.117622_b0105","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/jama.2022.13044","article-title":"Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement","volume":"328","author":"Mangione","year":"2022","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.bcp.2025.117622_b0110","first-page":"1","article-title":"Role of statins in coronary artery disease","volume":"49","author":"Nakagawa","year":"2013","journal-title":"Chonnam Med. J."},{"key":"10.1016\/j.bcp.2025.117622_b0115","doi-asserted-by":"crossref","first-page":"358","DOI":"10.12968\/bjcn.2021.26.7.358","article-title":"Statins to reduce cholesterol and cardiovascular disease in the community","volume":"26","author":"Mendes","year":"2021","journal-title":"Br. J. Community Nurs."},{"key":"10.1016\/j.bcp.2025.117622_b0120","doi-asserted-by":"crossref","first-page":"243","DOI":"10.2174\/092986707779313381","article-title":"Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis: beneficial effects of statins","volume":"14","author":"Lahera","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.bcp.2025.117622_b0125","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.repc.2015.09.006","article-title":"Statins and oxidative stress in chronic heart failure","volume":"35","author":"Costa","year":"2016","journal-title":"Rev. Port. Cardiol."},{"key":"10.1016\/j.bcp.2025.117622_b0130","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.atherosclerosis.2016.01.044","article-title":"Effects of simvastatin, ezetimibe and simvastatin\/ezetimibe on mitochondrial function and leukocyte\/endothelial cell interactions in patients with hypercholesterolemia","volume":"247","author":"Hernandez-Mijares","year":"2016","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.bcp.2025.117622_b0135","doi-asserted-by":"crossref","DOI":"10.1016\/j.crphar.2022.100088","article-title":"Simvastatin ameliorates oxidative stress levels in HepG2 cells and hyperlipidemic rats","volume":"3","author":"Verma","year":"2022","journal-title":"Curr. Res. Pharmacol. Drug Discovery"},{"key":"10.1016\/j.bcp.2025.117622_b0140","first-page":"6321","article-title":"Simvastatin alleviates inflammation and oxidative stress in rats with cerebral hemorrhage through Nrf2-ARE signaling pathway","volume":"23","author":"Zhang","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"10.1016\/j.bcp.2025.117622_b0145","doi-asserted-by":"crossref","first-page":"46219","DOI":"10.18632\/oncotarget.10078","article-title":"Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K\/Akt pathway in colon cancer","volume":"7","author":"Jang","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.bcp.2025.117622_b0150","doi-asserted-by":"crossref","first-page":"871","DOI":"10.3390\/antiox10060871","article-title":"Effects of folic acid supplementation on oxidative stress markers: a systematic review and meta-analysis of randomized controlled trials","volume":"10","author":"Asbaghi","year":"2021","journal-title":"Antioxidants"},{"key":"10.1016\/j.bcp.2025.117622_b0155","doi-asserted-by":"crossref","DOI":"10.3390\/molecules26123731","article-title":"The concept of folic acid in health and disease","volume":"26","author":"Shulpekova","year":"2021","journal-title":"Molecules"},{"key":"10.1016\/j.bcp.2025.117622_b0160","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2017.00585","article-title":"A meta-analysis of folic acid in combination with anti-hypertension drugs in patients with hypertension and hyperhomocysteinemia","volume":"8","author":"Wang","year":"2017","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.bcp.2025.117622_b0165","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1186\/s12885-019-6270-4","article-title":"Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer","volume":"19","author":"Martin","year":"2019","journal-title":"BMC Cancer"},{"key":"10.1016\/j.bcp.2025.117622_b0170","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2020.115213","article-title":"Heart slice culture system reliably demonstrates clinical drug-related cardiotoxicity","volume":"406","author":"Miller","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.bcp.2025.117622_b0175","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.ijdevneu.2011.06.004","article-title":"Development of an animal model for chronic mild hyperhomocysteinemia and its response to oxidative damage","volume":"29","author":"Scherer","year":"2011","journal-title":"Int. J. Dev. Neurosci."},{"key":"10.1016\/j.bcp.2025.117622_b0180","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12012-010-9094-7","article-title":"Homocysteine induces oxidative-nitrative stress in heart of rats: Prevention by folic acid","volume":"11","author":"Kolling","year":"2011","journal-title":"Cardiovasc. Toxicol."},{"key":"10.1016\/j.bcp.2025.117622_b0185","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.nutres.2017.01.007","article-title":"1,25-Dihydroxyvitamin D3 prevents deleterious effects of homocysteine on mitochondrial function and redox status in heart slices","volume":"38","author":"Longoni","year":"2017","journal-title":"Nutr. Res."},{"key":"10.1016\/j.bcp.2025.117622_b0190","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.3390\/nu14122397","article-title":"Absorption and tissue distribution of folate forms in rats: indications for specific folate form supplementation during pregnancy","volume":"14","author":"Bobrowski-Khoury","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.bcp.2025.117622_b0195","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1007\/s12035-017-0425-6","article-title":"Folic acid protects against glutamate-induced excitotoxicity in hippocampal slices through a mechanism that implicates inhibition of GSK-3\u03b2 and iNOS","volume":"55","author":"Budni","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.bcp.2025.117622_b0200","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jpba.2019.02.004","article-title":"Role of esterase mediated hydrolysis of simvastatin in human and rat blood and its impact on pharmacokinetic profiles of simvastatin and its active metabolite in rat","volume":"168","author":"Li","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"10.1016\/j.bcp.2025.117622_b0205","doi-asserted-by":"crossref","first-page":"248","DOI":"10.4062\/biomolther.2011.19.2.248","article-title":"Evaluation of pharmacokinetics of simvastatin and its pharmacologically active metabolite from controlled-release tablets of simvastatin in rodent and canine animal models","volume":"19","author":"Shanmugam","year":"2011","journal-title":"Biomol. Ther. (Seoul)"},{"key":"10.1016\/j.bcp.2025.117622_b0210","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12935-023-02890-1","article-title":"Paradoxical effects of statins on endothelial and cancer cells: the impact of concentrations","volume":"23","author":"Ahmadi","year":"2023","journal-title":"Cancer Cell Int."},{"key":"10.1016\/j.bcp.2025.117622_b0215","doi-asserted-by":"crossref","first-page":"e2584","DOI":"10.1371\/journal.pone.0002584","article-title":"The pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies","volume":"3","author":"Medina","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.bcp.2025.117622_b0220","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0008-6363(01)00306-6","article-title":"Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: an ex vivo study in isolated working rat hearts","volume":"51","author":"Di Napoli","year":"2001","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.bcp.2025.117622_b0225","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1021\/tx00026a012","article-title":"Evaluation of the Probe 2\u2032,7\u2032-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress","volume":"5","author":"LeBel","year":"1992","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.bcp.2025.117622_b0230","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.bcp.2025.117622_b0235","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0076-6879(90)86134-H","article-title":"Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal","volume":"186","author":"Esterbauer","year":"1990","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.bcp.2025.117622_b0240","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0304-3940(01)01636-6","article-title":"Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer\u2019s disease","volume":"302","author":"Aksenov","year":"2001","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.bcp.2025.117622_b0245","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0003-2697(82)90118-X","article-title":"Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids","volume":"126","author":"Green","year":"1982","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.bcp.2025.117622_b0250","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0014-5793(85)80613-X","article-title":"Product of extracellular-superoxide dismutase catalysis","volume":"184","author":"Marklund","year":"1985","journal-title":"FEBS Lett."},{"key":"10.1016\/j.bcp.2025.117622_b0255","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"[13] Catalase in Vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.bcp.2025.117622_b0260","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0076-6879(81)77046-0","article-title":"Glutathione peroxidase","volume":"77","author":"Wendel","year":"1981","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.bcp.2025.117622_b0265","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.bcp.2025.117622_b0270","doi-asserted-by":"crossref","first-page":"8538","DOI":"10.1007\/s12035-018-1003-2","article-title":"Kynurenic acid restores Nrf2 levels and prevents quinolinic acid-induced toxicity in rat striatal slices","volume":"55","author":"Ferreira","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.bcp.2025.117622_b0275","doi-asserted-by":"crossref","unstructured":"O.H. Lowry, N.J. Rosebrough, A.L. Farr, R.J. Randall, Protein measurement with the folin phenol reagent*, (1951). https:\/\/doi.org\/10.1016\/S0021-9258(19)52451-6.","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"10.1016\/j.bcp.2025.117622_b0280","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":"Mm","year":"1976","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.bcp.2025.117622_b0285","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s12640-022-00484-9","article-title":"Quinolinic Acid impairs redox homeostasis, bioenergetic, and cell signaling in rat striatum slices: prevention by coenzyme Q10","volume":"40","author":"Ferreira","year":"2022","journal-title":"Neurotox. Res."},{"key":"10.1016\/j.bcp.2025.117622_b0290","article-title":"Homocysteine induces mitochondrial dysfunction involving the crosstalk between oxidative stress and mitochondrial pSTAT3 in rat ischemic brain","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bcp.2025.117622_b0295","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1161\/01.ATV.20.5.1182","article-title":"Hyperhomocysteinemia and oxidative stress: time for a reality check?","volume":"20","author":"Jacobsen","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.bcp.2025.117622_b0300","doi-asserted-by":"crossref","unstructured":"J. Aguilar Diaz De Leon, C.R. Borges, Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay, J. Visualized Exp. 2020 (2020). https:\/\/doi.org\/10.3791\/61122.","DOI":"10.3791\/61122"},{"key":"10.1016\/j.bcp.2025.117622_b0305","doi-asserted-by":"crossref","DOI":"10.3390\/antiox10060871","article-title":"Effects of folic acid supplementation on oxidative stress markers: a systematic review and meta-analysis of randomized controlled trials","volume":"10","author":"Asbaghi","year":"2021","journal-title":"Antioxidants"},{"key":"10.1016\/j.bcp.2025.117622_b0310","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/S0891-5849(01)00543-3","article-title":"Free radical scavenging behavior of folic acid: Evidence for possible antioxidant activity","volume":"30","author":"Joshi","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.bcp.2025.117622_b0315","doi-asserted-by":"crossref","first-page":"14276","DOI":"10.1021\/acs.jafc.3c01851","article-title":"Folic acid protects against ethanol-induced hepatic mitophagy imbalance by ROS scavenging and attenuating the elevated Hcy levels","volume":"71","author":"Zhao","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.bcp.2025.117622_b0320","doi-asserted-by":"crossref","first-page":"L575","DOI":"10.1152\/ajplung.00428.2007","article-title":"Endothelial cell barrier protection by simvastatin: GTPase regulation and NADPH oxidase inhibition","volume":"295","author":"Chen","year":"2008","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"10.1016\/j.bcp.2025.117622_b0325","doi-asserted-by":"crossref","first-page":"7040","DOI":"10.2174\/1381612823666170926130338","article-title":"Statins and oxidative stress in the cardiovascular system","volume":"23","author":"Margaritis","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.bcp.2025.117622_b0330","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1161\/ATVBAHA.107.154492","article-title":"Statin treatment and 3\u2032 polyadenylation of eNOS mRNA","volume":"27","author":"Kosmidou","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.bcp.2025.117622_b0335","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3390\/antiox9050393","article-title":"Nitric oxide modulation by folic acid fortification","volume":"9","author":"Taira","year":"2020","journal-title":"Antioxidants"},{"key":"10.1016\/j.bcp.2025.117622_b0340","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.gene.2014.05.005","article-title":"Creatine prevents the imbalance of redox homeostasis caused by homocysteine in skeletal muscle of rats","volume":"545","author":"Kolling","year":"2014","journal-title":"Gene"},{"key":"10.1016\/j.bcp.2025.117622_b0345","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neuint.2008.08.011","article-title":"Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid","volume":"54","author":"Matt\u00e9","year":"2009","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.bcp.2025.117622_b0350","article-title":"A systematic review and meta-analysis of the effect of statins on glutathione peroxidase, superoxide dismutase, and catalase","volume":"10","author":"Zinellu","year":"2021","journal-title":"Antioxidants"},{"key":"10.1016\/j.bcp.2025.117622_b0355","first-page":"721","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"2018","author":"Bellezza","year":"1865","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.bcp.2025.117622_b0360","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.2174\/1871530320666200604160614","article-title":"Are oxidative stress and inflammation mediators of bone loss due to estrogen deficiency? A review of current evidence","volume":"20","author":"Mohamad","year":"2020","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"10.1016\/j.bcp.2025.117622_b0365","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/218749","article-title":"Efficacy of a low dose of estrogen on antioxidant defenses and heart rate variability","volume":"2014","author":"Campos","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.bcp.2025.117622_b0370","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.amjhyper.2006.01.008","article-title":"Estrogen treatment enhances nitric oxide bioavailability in normotensive but not hypertensive rats","volume":"19","author":"Hamilton","year":"2006","journal-title":"Am. J. Hypertens."},{"key":"10.1016\/j.bcp.2025.117622_b0375","doi-asserted-by":"crossref","DOI":"10.1152\/physiol.2025.40.S1.0643","article-title":"Sex differences and the role of endothelial Nrf2 in the modulation of blood pressure and vascular reactivity","volume":"40","author":"Dhyani","year":"2025","journal-title":"Physiology"},{"key":"10.1016\/j.bcp.2025.117622_b0380","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.3390\/cells13151247","article-title":"Sex differences affect the NRF2 signaling pathway in the early phase of liver steatosis: a high-fat-diet-fed rat model supplemented with liquid fructose","volume":"13","author":"Di Veroli","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.bcp.2025.117622_b0385","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.70371","article-title":"Chronic stress elicits sex\u2010specific mitochondrial respiratory functional changes in the rat heart","volume":"13","author":"Odendaal-Gambrell","year":"2025","journal-title":"Physiol. Rep."},{"key":"10.1016\/j.bcp.2025.117622_b0390","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s10571-019-00674-8","article-title":"Chronic mild Hyperhomocysteinemia impairs energy metabolism, promotes DNA damage and induces a Nrf2 response to oxidative stress in rats brain","volume":"39","author":"dos Santos","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"10.1016\/j.bcp.2025.117622_b0395","doi-asserted-by":"crossref","first-page":"407","DOI":"10.2147\/JIR.S140188","article-title":"Mechanisms of NF-\u03baB p65 and strategies for therapeutic manipulation","volume":"11","author":"Giridharan","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"10.1016\/j.bcp.2025.117622_b0400","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1161\/01.RES.0000108264.67601.2C","article-title":"Hyperhomocysteinemia activates nuclear factor-\u03baB in endothelial cells via oxidative stress","volume":"94","author":"Au-Yeung","year":"2004","journal-title":"Circ. Res."},{"key":"10.1016\/j.bcp.2025.117622_b0405","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12872-024-04046-z","article-title":"Catalpol inhibits HHcy-induced EndMT in endothelial cells by modulating ROS\/NF-\u03baB signaling","volume":"24","author":"Wu","year":"2024","journal-title":"BMC Cardiovasc. Disord."},{"key":"10.1016\/j.bcp.2025.117622_b0410","article-title":"Post-translational Modifications of I\u03baB\u03b1: The State of the Art","volume":"8","author":"Wang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.bcp.2025.117622_b0415","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bcp.2025.117622_b0420","article-title":"Interleukin-6 and cardiovascular events in healthy adults: MESA","volume":"3","author":"Khan","year":"2024","journal-title":"JACC: Advances"},{"key":"10.1016\/j.bcp.2025.117622_b0425","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1016\/j.jacc.2020.08.026","article-title":"Interleukin-1\u03b2 and risk of premature death in patients with myocardial infarction","volume":"76","author":"Silvain","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.bcp.2025.117622_b0430","doi-asserted-by":"crossref","first-page":"979","DOI":"10.3390\/biom14080979","article-title":"Major adverse cardiovascular events: the importance of serum levels and haplotypes of the anti-inflammatory cytokine interleukin 10","volume":"14","author":"Schulz","year":"2024","journal-title":"Biomolecules"},{"key":"10.1016\/j.bcp.2025.117622_b0435","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s10753-024-02140-0","article-title":"Phosphorylation of serine 536 of p65(RelA) downregulates inflammatory responses","volume":"48","author":"Aoki","year":"2024","journal-title":"Inflammation"},{"key":"10.1016\/j.bcp.2025.117622_b0440","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2022.102539","article-title":"Differential endothelial hydrogen peroxide signaling via Nox isoforms: Critical roles for Rac1 and modulation by statins","volume":"58","author":"Waldeck-Weiermair","year":"2022","journal-title":"Redox Biol."},{"key":"10.1016\/j.bcp.2025.117622_b0445","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12950-024-00420-y","article-title":"Regulatory effects of statins on CCL2\/CCR2 axis in cardiovascular diseases: new insight into pleiotropic effects of statins","volume":"21","author":"Gholamalizadeh","year":"2024","journal-title":"J. Inflamm. (Lond.)"},{"key":"10.1016\/j.bcp.2025.117622_b0450","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.3390\/ijms25094958","article-title":"Use of statins in heart failure with preserved ejection fraction: current evidence and perspectives","volume":"25","author":"Ovchinnikov","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bcp.2025.117622_b0455","unstructured":"T. Hu, B. Chen, S. Zhou, J. Mao, Simvastatin inhibits inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages through the microRNA-22\/Cyr61 axis, Int. J. Clin. Exp. Pathol. 11 (2018) 3925. https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC6962815\/ (accessed July 31, 2025)."},{"key":"10.1016\/j.bcp.2025.117622_b0460","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/1839762","article-title":"Simvastatin posttreatment controls inflammation and improves bacterial clearance in experimental sepsis","volume":"2020","author":"De Jesus Oliveira","year":"2020","journal-title":"Mediators Inflamm."},{"key":"10.1016\/j.bcp.2025.117622_b0465","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12986-017-0224-0","article-title":"Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity","volume":"14","author":"Li","year":"2017","journal-title":"Nutr. Metab. (Lond.)"},{"key":"10.1016\/j.bcp.2025.117622_b0470","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1161\/CIRCULATIONAHA.107.725481","article-title":"High dose folic acid pre-treatment blunts cardiac dysfunction during ischemia coupled to maintenance of high energy phosphates and reduces post-reperfusion injury","volume":"117","author":"Moens","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.bcp.2025.117622_b0475","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00011-011-0337-2","article-title":"Folic acid inhibits lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages by suppressing MAPKs and NF-\u03baB activation","volume":"60","author":"Feng","year":"2011","journal-title":"Inflamm. Res."},{"key":"10.1016\/j.bcp.2025.117622_b0480","article-title":"Folic acid represses hypoxia-induced inflammation in THP-1 cells through inhibition of the PI3K\/Akt\/HIF-1\u03b1 pathway","volume":"11","author":"Huang","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.bcp.2025.117622_b0485","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.3390\/ijms22126259","article-title":"Homocysteine and age-related central nervous system diseases: role of inflammation","volume":"22","author":"Tawfik","year":"2021","journal-title":"Int. J. Mole. Sci."},{"key":"10.1016\/j.bcp.2025.117622_b0490","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20181117","article-title":"Estrogen ameliorates allergic airway inflammation by regulating activation of NLRP3 in mice","volume":"39","author":"Cheng","year":"2019","journal-title":"Biosci. Rep."}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225008871?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225008871?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:14:54Z","timestamp":1781698494000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295225008871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":98,"alternative-id":["S0006295225008871"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117622","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sex\u2010specific mitigation of oxidative and inflammatory cardiac alterations by folic acid and simvastatin in chronic mild hyperhomocysteinemia","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117622","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117622"}}