{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:33:43Z","timestamp":1776792823871,"version":"3.51.2"},"reference-count":69,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1822\/12"],"award-info":[{"award-number":["1822\/12"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Osteoporosis is a bone-debilitating disease, demonstrating a higher prevalence in post-menopausal women due to estrogen deprivation. One of the main mechanisms underlying menopause-related bone loss is oxidative stress. S-allylmercapto-N-acetylcysteine (ASSNAC) is a nuclear factor erythroid 2-related factor 2 (Nrf2) activator and cysteine supplier, previously shown to have anti-oxidation protective effects in cultured cells and animal models. Here, we studied the therapeutic potential of ASSNAC with and without Alendronate in ovariectomized (OVX) female mice. The experimental outcome included (i) femur and L3 lumbar vertebra morphometry via Micro-Computed Tomography (\u03bcCT); (ii) bone remodeling (formation vs. resorption); and (iii) oxidative stress markers in bone marrow (BM) cells. Four weeks after OVX, there was a significant bone loss that remained evident after 8 weeks, as demonstrated via \u00b5CT in the femur (cortical and trabecular bone compartments) and vertebra (trabecular bone). ASSNAC at a dose of 50 mg\/Kg\/day prevented bone loss after the four-week treatment but had no significant effect after 8 weeks, while ASSNAC at a dose of 20 mg\/Kg\/day significantly protected against bone loss after 8 weeks of treatment. Alendronate prevented ovariectomy-induced bone loss, and combining it with ASSNAC further augmented this effect. OVX mice demonstrated high serum levels of both C-terminal cross-linked telopeptides of type I collagen (CTX) (bone resorption) and procollagen I N-terminal propeptide (P1NP) (bone formation) after 2 weeks, and these returned to control levels after 8 weeks. Alendronate, ASSNAC and their combination decreased CTX and increased P1NP. Alendronate induced oxidative stress as reflected by decreased glutathione and increased malondialdehyde (MDA) levels, and combining it with ASSNAC partially attenuated these changes. These results portray the therapeutic potential of ASSNAC for the management of post-menopausal osteoporosis. Furthermore, ASSNAC ameliorates the Alendronate-associated oxidative stress, suggesting its potential to prevent Alendronate side effects as well as improve its bone-protective effect.<\/jats:p>","DOI":"10.3390\/antiox13040474","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T08:22:44Z","timestamp":1713342164000},"page":"474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["S-Allylmercapto-N-Acetylcysteine (ASSNAC) Attenuates Osteoporosis in Ovariectomized (OVX) Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8717-5505","authenticated-orcid":false,"given":"Itay","family":"Bleichman","sequence":"first","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry and Goldschleger Eye Research Institute, School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahar","family":"Hiram-Bab","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Anthropology, School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-0631","authenticated-orcid":false,"given":"Yankel","family":"Gabet","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Anthropology, School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-0624","authenticated-orcid":false,"given":"Naphtali","family":"Savion","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry and Goldschleger Eye Research Institute, School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1172\/JCI27071","article-title":"Pathogenesis of Osteoporosis: Concepts, Conflicts, and Prospects","volume":"115","author":"Raisz","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/0004563218759371","article-title":"The Bone Remodelling Cycle","volume":"55","author":"Kenkre","year":"2018","journal-title":"Ann. Clin. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1242\/jcs.113.3.377","article-title":"The Cell Biology of Osteoclast Function","volume":"113","author":"Zhao","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.tem.2012.03.008","article-title":"Estrogen and the Skeleton","volume":"23","author":"Khosla","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0169-6009(92)90809-R","article-title":"On the Rat Model of Human Osteopenias and Osteoporosis","volume":"18","author":"Frost","year":"1992","journal-title":"Bone Miner."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/8756-3282(95)80027-N","article-title":"Temporal Changes in Cancellous Bone-Structure of Rats Immediately After Ovariectomy","volume":"16","author":"Dempster","year":"1995","journal-title":"Bone"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0169-6009(91)90124-I","article-title":"The Ovariectomized Rat Model of Postmenopausal Bone Loss","volume":"15","author":"Kalu","year":"1991","journal-title":"Bone Miner."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejphar.2015.03.028","article-title":"Animal Models for Osteoporosis","volume":"759","author":"Komori","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/aps.2014.111","article-title":"Antidepressant Bupropion Exerts Alleviating Properties in an Ovariectomized Osteoporotic Rat Model","volume":"36","author":"Abuohashish","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S125","DOI":"10.1016\/8756-3282(95)00285-L","article-title":"FDA guidelines and animal-models for osteoporosis","volume":"17","author":"Thompson","year":"1995","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7266","DOI":"10.3390\/molecules15107266","article-title":"The Nrf2 System as a Potential Target for the Development of Indirect Antioxidants","volume":"15","author":"Jung","year":"2010","journal-title":"Molecules"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1021\/pr400050u","article-title":"Paraoxonase-1 Deficiency Is Associated with Severe Liver Steatosis in Mice Fed a High-Fat High-Cholesterol Diet: A Metabolomic Approach","volume":"12","author":"Kensicki","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.abb.2008.03.037","article-title":"Osteoclast Lineage and Function","volume":"473","author":"Vaananen","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7067984","DOI":"10.1155\/2016\/7067984","article-title":"Oxidative Stress-Related Biomarkers in Postmenopausal Osteoporosis: A Systematic Review and Meta-Analyses","volume":"2016","author":"Zhou","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.freeradbiomed.2021.12.010","article-title":"Inhibition of Nrf2 Degradation Alleviates Age-Related Osteoporosis Induced by 1,25-Dihydroxyvitamin D Deficiency","volume":"178","author":"Yang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1530\/JOE-18-0691","article-title":"Monomethylfumarate Protects against Ovariectomy-Related Changes in Body Composition","volume":"243","author":"Bollag","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.freeradbiomed.2019.10.412","article-title":"Melatonin Restores the Osteoporosis-Impaired Osteogenic Potential of Bone Marrow Mesenchymal Stem Cells by Preserving SIRT1-Mediated Intracellular Antioxidant Properties","volume":"146","author":"Chen","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5582","DOI":"10.1002\/fsn3.3516","article-title":"Orientin Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis via Suppressing ROS Production","volume":"11","author":"Zheng","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1056\/NEJMoa0802633","article-title":"Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy","volume":"360","author":"Weinstein","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/jbmr.5650080713","article-title":"Effects of Combined Prostaglandin and Alendronate Treatment on the Histomorphometry and Biomechanical Properties of Bone in Ovariectomized Rats","volume":"8","author":"Lauritzen","year":"1993","journal-title":"J. Bone Miner. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1210\/jc.2003-031672","article-title":"Prevention of Postmenopausal Bone Loss: Six-Year Results from the Early Postmenopausal Intervention Cohort Study","volume":"89","author":"McClung","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1126\/science.289.5484.1508","article-title":"Therapeutic Approaches to Bone Diseases","volume":"289","author":"Rodan","year":"2000","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Park, J.-H., Park, E.-K., Koo, D.-W., Lee, S., Lee, S.-H., Kim, G.-T., and Lee, S.-G. (2017). Compliance and Persistence with Oral Bisphosphonates for the Treatment of Osteoporosis in Female Patients with Rheumatoid Arthritis. BMC Musculoskelet. Disord., 18.","DOI":"10.1186\/s12891-017-1514-4"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s12011-013-9659-y","article-title":"Basic Fibroblast Growth Factor Attenuates Bisphosphonate-Induced Oxidative Injury but Decreases Zinc and Copper Levels in Oral Epithelium of Rat","volume":"153","author":"Kocer","year":"2013","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1016\/j.transproceed.2010.06.017","article-title":"Oxidant and Antioxidant Activity in Rabbit Livers Treated With Zoledronic Acid","volume":"42","author":"Karabulut","year":"2010","journal-title":"Transplant. Proc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/17446651.2017.1256199","article-title":"Bisphosphonates in the Treatment of Osteoporosis: A Review of Skeletal Safety Concerns","volume":"12","author":"Habib","year":"2017","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1302\/0301-620X.93B10.26924","article-title":"Long-Term Bisphosphonate Usage and Subtrochanteric Insufficiency Fractures: A Cause for Concern?","volume":"93","author":"Yoon","year":"2011","journal-title":"J. Bone Jt. Surg.-Br. Vol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: Now and the Future","volume":"377","author":"Rachner","year":"2011","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1002\/jbmr.1719","article-title":"Incidence of Atypical Nontraumatic Diaphyseal Fractures of the Femur","volume":"27","author":"Dell","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.oooo.2018.09.008","article-title":"Medication-Related Osteonecrosis of the Jaw: Definition and Best Practice for Prevention, Diagnosis, and Treatment","volume":"127","author":"Mendes","year":"2019","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115453","DOI":"10.1016\/j.bone.2020.115453","article-title":"Biological Activity Is Not Suppressed in Mid-Shaft Stress Fracture of the Bowed Femoral Shaft Unlike in \u201cTypical\u201d Atypical Subtrochanteric Femoral Fracture: A Proposed Theory of Atypical Femoral Fracture Subtypes","volume":"137","author":"Oh","year":"2020","journal-title":"Bone"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/JPER.19-0385","article-title":"Bisphosphonate-Induced Reactive Oxygen Species Inhibit Proliferation and Migration of Oral Fibroblasts: A Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaw","volume":"91","author":"Taniguchi","year":"2020","journal-title":"J. Periodontol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/jop.12151","article-title":"Oxidative Stress in Bisphosphonate-Related Osteonecrosis of the Jaws","volume":"43","author":"Bagan","year":"2014","journal-title":"J. Oral Pathol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/0896-6273(89)90043-3","article-title":"Glutamate toxicity in a neuronal cell-line involves inhibition of cystine transport leading to oxidative stress","volume":"2","author":"Murphy","year":"1989","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.3390\/molecules15117792","article-title":"Nutraceutical Antioxidants as Novel Neuroprotective Agents","volume":"15","author":"Kelsey","year":"2010","journal-title":"Molecules"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1006\/bbrc.1999.1109","article-title":"Up-Regulation of the Human \u03b3-Glutamylcysteine Synthetase Regulatory Subunit Gene Involves Binding of Nrf-2 to an Electrophile Responsive Element","volume":"261","author":"Moinova","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13885","DOI":"10.3390\/ijms160613885","article-title":"Dimethyl Fumarate Protects Neural Stem\/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1\/2 MAPK Pathway","volume":"16","author":"Wang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.pharmtox.46.120604.141046","article-title":"Cell Survival Responses to Environmental Stresses via the Keap1-Nrf2-ARE Pathway","volume":"47","author":"Kensler","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"726590","DOI":"10.1155\/2014\/726590","article-title":"Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis","volume":"2014","author":"Ibanez","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sun, X., Xie, Z., Hu, B., Zhang, B., Ma, Y., Pan, X., Huang, H., Wang, J., Zhao, X., and Jie, Z. (2020). The Nrf2 Activator RTA-408 Attenuates Osteoclastogenesis by Inhibiting STING Dependent NF-\u039ab Signaling. Redox Biol., 28.","DOI":"10.1016\/j.redox.2019.101309"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00394-008-0762-3","article-title":"Allicin Up-Regulates Cellular Glutathione Level in Vascular Endothelial Cells","volume":"48","author":"Eliav","year":"2009","journal-title":"Eur. J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.freeradbiomed.2011.01.028","article-title":"S-Allylmercapto-N-Acetylcysteine up-Regulates Cellular Glutathione and Protects Vascular Endothelial Cells from Oxidative Stress","volume":"50","author":"Izigov","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.neulet.2014.09.034","article-title":"S-Allylmercapto-N-Acetylcysteine (ASSNAC) Protects Cultured Nerve Cells from Oxidative Stress and Attenuates Experimental Autoimmune Encephalomyelitis","volume":"583","author":"Savion","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Savion, N., Levine, A., Kotev-Emeth, S., Abu-Shach, U.B., and Broday, L. (2018). S-Allylmercapto-N-Acetylcysteine Protects against Oxidative Stress and Extends Lifespan in Caenorhabditis Elegans. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194780"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Savion, N., Dahamshi, S., Morein, M., and Kotev-Emeth, S. (2019). S-Allylmercapro-N-Acetylcysteine Attenuates the Oxidation-Induced Lens Opacification and Retinal Pigment Epithelial Cell Death in Vitro. Antioxidants, 8.","DOI":"10.3390\/antiox8010025"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1177\/15353702221095047","article-title":"S-Allylmercapto-N-Acetylcysteine Protects Bone Cells from Oxidation and Improves Femur Microarchitecture in Healthy and Diabetic Mice","volume":"247","author":"Gabet","year":"2022","journal-title":"Exp. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Ye, W., Liu, Y., Niu, D., Zhao, X., Li, G., Qu, Y., and Zhao, Z. (2023). S-Allylmercapto-N-Acetylcysteine Ameliorates Pulmonary Fibrosis in Mice via Nrf2 Pathway Activation and NF-\u03baB, TGF-\u03921\/Smad2\/3 Pathway Suppression. Biomed. Pharmacother., 157.","DOI":"10.1016\/j.biopha.2022.114018"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.bone.2012.06.018","article-title":"Bisphosphonates Improve Trabecular Bone Mass and Normalize Cortical Thickness in Ovariectomized, Osteoblast Connexin43 Deficient Mice","volume":"51","author":"Watkins","year":"2012","journal-title":"Bone"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/jcp.25895","article-title":"Bone Loss in C57BL\/6J-OlaHsd Mice, a Substrain of C57BL\/6J Carrying Mutated Alpha-Synuclein and Multimerin-1 Genes","volume":"233","author":"Liron","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for Assessment of Bone Microstructure in Rodents Using Micro\u2013Computed Tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1182\/blood-2010-01-263830","article-title":"Krox20\/EGR2 Deficiency Accelerates Cell Growth and Differentiation in the Monocytic Lineage and Decreases Bone Mass","volume":"116","author":"Gabet","year":"2010","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/S0076-6879(85)13073-9","article-title":"Determination of Glutathione and Glutathione Disulfide in Biological Samples","volume":"113","author":"Anderson","year":"1985","journal-title":"Methods Enzymol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein Measurement with the Folin Phenol Reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0076-6879(90)86135-I","article-title":"Malondialdehyde Determination as Index of Lipid-Peroxidation","volume":"186","author":"Draper","year":"1990","journal-title":"Methods Enzymol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Oh, Y., Ahn, C.-B., Cho, W.H., Yoon, N.Y., and Je, J.-Y. (2020). Anti-Osteoporotic Effects of Antioxidant Peptides PIISVYWK and FSVVPSPK from Mytilus Edulis on Ovariectomized Mice. Antioxidants, 9.","DOI":"10.3390\/antiox9090866"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.freeradbiomed.2020.12.235","article-title":"Apelin-13 Induces Mitophagy in Bone Marrow Mesenchymal Stem Cells to Suppress Intracellular Oxidative Stress and Ameliorate Osteoporosis by Activation of AMPK Signaling Pathway","volume":"163","author":"Chen","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.freeradbiomed.2021.03.008","article-title":"Ginkgolide B Monotherapy Reverses Osteoporosis by Regulating Oxidative Stress-Mediated Bone Homeostasis","volume":"168","author":"Lee","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kim, B., Lee, S.-H., Song, S.-J., Kim, W.H., Song, E.-S., Lee, J.-C., Lee, S.-J., Han, D.-W., and Lee, J.-H. (2019). Protective Effects of Melon Extracts on Bone Strength, Mineralization, and Metabolism in Rats with Ovariectomy-Induced Osteoporosis. Antioxidants, 8.","DOI":"10.3390\/antiox8080306"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00774-023-01416-z","article-title":"Resveratrol Prevents Ovariectomy-Induced Bone Quality Deterioration by Improving the Microarchitectural and Biophysicochemical Properties of Bone","volume":"41","author":"Ozturk","year":"2023","journal-title":"J. Bone Miner. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.freeradbiomed.2023.01.017","article-title":"Corylifol A Protects against Ovariectomized-Induced Bone Loss and Attenuates RANKL-Induced Osteoclastogenesis via ROS Reduction, ERK Inhibition, and NFATc1 Activation","volume":"196","author":"Xu","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_61","unstructured":"Flores, M.V. (2013). Topics in Osteoporosis, IntechOpen."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00223-007-9101-6","article-title":"Short-Term Changes in Serum PINP Predict Long-Term Changes in Trabecular Bone in the Rat Ovariectomy Model","volume":"82","author":"Rissanen","year":"2008","journal-title":"Calcif. Tissue Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1002\/jbmr.489","article-title":"Cytoplasmic Superoxide Causes Bone Fragility Owing to Low-Turnover Osteoporosis and Impaired Collagen Cross-Linking","volume":"26","author":"Nojiri","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/bbrc.2001.5747","article-title":"Association between Oxidative Stress and Bone Mineral Density","volume":"288","author":"Basu","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1515\/cclm-2012-0095","article-title":"Bone Mass Density Selectively Correlates with Serum Markers of Oxidative Damage in Post-Menopausal Women","volume":"51","author":"Cervellati","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1172\/JCI200318859","article-title":"A Crucial Role for Thiol Antioxidants in Estrogen-Deficiency Bone Loss","volume":"112","author":"Lean","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ejphar.2011.11.024","article-title":"Protection against Osteoporosis by Statins Is Linked to a Reduction of Oxidative Stress and Restoration of Nitric Oxide Formation in Aged and Ovariectomized Rats","volume":"674","author":"Yin","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1080\/21655979.2021.1928930","article-title":"Parathyroid Hormone-Related Protein Inhibits Nitrogen-Containing Bisphosphonate-Induced Apoptosis of Human Periodontal Ligament Fibroblasts by Activating MKP1 Phosphatase","volume":"12","author":"Liu","year":"2021","journal-title":"Bioengineered"},{"key":"ref_69","first-page":"1440","article-title":"Osteonecrosis of the Jaws Caused by Bisphosphonate Treatment and Oxidative Stress in Mice","volume":"17","author":"Tamaoka","year":"2019","journal-title":"Exp. Ther. Med."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/4\/474\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:29:11Z","timestamp":1760106551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/4\/474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,17]]},"references-count":69,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["antiox13040474"],"URL":"https:\/\/doi.org\/10.3390\/antiox13040474","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,17]]}}}