{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:20:40Z","timestamp":1778754040344,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006541","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["IND2018\/BMD-9485"],"award-info":[{"award-number":["IND2018\/BMD-9485"]}],"id":[{"id":"10.13039\/501100006541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Sr\/Zn phytate compounds have been shown interest in biomaterial science, specifically in dental implantology, due to their antimicrobial effects against Streptococcus\u00a0mutans and their capacity to form bioactive coatings. Phytic acid is a natural chelating compound that shows antioxidant and osteogenic properties that can play an important role in bone remodelling processes affected by oxidative stress environments, such as those produced during infections. The application of non-protein cell-signalling molecules that regulate both bone and ROS homeostasis is a promising strategy for the regeneration of bone tissues affected by oxidative stress processes. In this context, phytic acid (PA) emerged as an excellent option since its antioxidant and osteogenic properties can play an important role in bone remodelling processes. In this study, we explored the antioxidant and osteogenic properties of two metallic PA complexes bearing bioactive cations, i.e., Sr2+ (SrPhy) and Zn2+ (ZnPhy), highlighting the effect of the divalent cations anchored to phytate moieties and their capability to modulate the PA properties. The in vitro features of the complexes were analyzed and compared with those of their precursor PA. The ferrozine\/FeCl2 method indicated that SrPhy exhibited a more remarkable ferrous ion affinity than ZnPhy, while the antioxidant activity demonstrated by a DPPH assay showed that only ZnPhy reduced the content of free radicals. Likewise, the antioxidant potential was assessed with RAW264.7 cell cultures. An ROS assay indicated again that ZnPhy was the only one to reduce the ROS content (20%), whereas all phytate compounds inhibited lipid peroxidation following the decreasing order of PA &gt; SrPhy &gt; ZnPhy. The in vitro evaluation of the phytate\u2019s osteogenic ability was performed using hMSC cells. The results showed tailored properties related to the cation bound in each complex. ZnPhy overexpressed ALP activity at 3 and 14 days, and SrPhy significantly increased calcium deposition after 21 days. This study demonstrated that Sr\/Zn phytates maintained the antioxidant and osteogenic properties of PA and can be used in bone regenerative therapies involving oxidative environments, such as infected implant coatings and periodontal tissues.<\/jats:p>","DOI":"10.3390\/pharmaceutics15020339","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:50:20Z","timestamp":1674107420000},"page":"339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["New Insights into the In Vitro Antioxidant Routes and Osteogenic Properties of Sr\/Zn Phytate Compounds"],"prefix":"10.3390","volume":"15","author":[{"given":"Gerardo","family":"Asensio","sequence":"first","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros (ICTP), CSIC. Calle Juan de la Cierva, 3, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3028-6228","authenticated-orcid":false,"given":"Marcela","family":"Mart\u00edn-del-Campo","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros (ICTP), CSIC. Calle Juan de la Cierva, 3, 28006 Madrid, Spain"},{"name":"Facultad de Estomatolog\u00eda, Universidad Aut\u00f3noma San Luis Potos\u00ed (UASLP), San Luis Potos\u00ed 78290, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-2553","authenticated-orcid":false,"given":"Rosa Ana","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros (ICTP), CSIC. Calle Juan de la Cierva, 3, 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-6736","authenticated-orcid":false,"given":"Luis","family":"Rojo","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros (ICTP), CSIC. Calle Juan de la Cierva, 3, 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28006 Madrid, Spain"},{"name":"Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy-Spanish National Research Council (SusPlast-CSIC), 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-8026","authenticated-orcid":false,"given":"Blanca","family":"V\u00e1zquez-Lasa","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros (ICTP), CSIC. Calle Juan de la Cierva, 3, 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28006 Madrid, Spain"},{"name":"Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy-Spanish National Research Council (SusPlast-CSIC), 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112020","DOI":"10.1016\/j.ejmech.2019.112020","article-title":"Bridging free radical chemistry with drug discovery: A promising way for finding novel drugs efficiently","volume":"189","author":"Liu","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_2","first-page":"119","article-title":"Oxidative Stress and Osteoimmunology: The two Missing Pieces of the Oral Osseointegration Puzzle","volume":"3","author":"Choukroun","year":"2011","journal-title":"Immunol. Res. Ther. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.11138\/ccmbm\/2017.14.1.209","article-title":"Oxidative stress in bone remodeling: Role of antioxidants","volume":"14","author":"Domazetovic","year":"2017","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/s00223-010-9393-9","article-title":"Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures","volume":"87","author":"Baek","year":"2010","journal-title":"Calcif. Tissue Int."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tian, Y., Ma, X., Yang, C., Su, P., Yin, C., and Qian, A.-R. (2017). The impact of oxidative stress on the bone system in response to the space special environment. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102132"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00774-020-01175-1","article-title":"Discovery of the RANKL\/RANK\/OPG system","volume":"39","author":"Yasuda","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jfda.2016.11.006","article-title":"Macrophages in oxidative stress and models to evaluate the antioxidant function of dietary natural compounds","volume":"25","author":"Castaneda","year":"2017","journal-title":"J. Food Drug Anal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of RANKL\/RANK\/OPG in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3027303","DOI":"10.1155\/2019\/3027303","article-title":"The Application of Hyaluronic Acid-Based Hydrogels in Bone and Cartilage Tissue Engineering","volume":"2019","author":"Li","year":"2019","journal-title":"Adv. Mater. Sci. Eng."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chemphyslip.2008.09.004","article-title":"Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and\/or pathological conditions","volume":"157","year":"2009","journal-title":"Chem. Phys. Lipids."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/00004630-198307000-00002","article-title":"Lipid peroxidation following thermal injury","volume":"4","author":"Sasaki","year":"1983","journal-title":"J. Burn Care Rehabil."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.bbrc.2016.10.086","article-title":"Lipid peroxidation in cell death","volume":"482","author":"Gaschler","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/anu.12614","article-title":"Effects of supplemental phytic acid on the apparent digestibility and utilization of dietary amino acids and minerals in juvenile grass carp ( Ctenopharyngodon idellus )","volume":"24","author":"Liu","year":"2017","journal-title":"Aquac. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8113","DOI":"10.1039\/D2GC02638D","article-title":"Performance and failure process of green recycling solutions for preparing high degradation resistance coating on biomedical magnesium alloys","volume":"24","author":"Qin","year":"2022","journal-title":"Green Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/978-1-4684-9111-1_11","article-title":"Phytic acid interactions with divalent cations in foods and in the gastrointestinal tract","volume":"249","author":"Erdman","year":"1989","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1021\/jf00121a010","article-title":"Removal of Phytic Acid and Protein-Phytic Acid Interactions in Rapeseed","volume":"32","author":"Serraino","year":"1984","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147307","DOI":"10.1155\/2013\/147307","article-title":"Phytic acid inhibits lipid peroxidation in vitro","volume":"2013","author":"Zajdel","year":"2013","journal-title":"Biomed Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11647","DOI":"10.1016\/S0021-9258(18)60858-0","article-title":"Phytic acid. A natural antioxidant","volume":"262","author":"Graf","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_20","first-page":"125","article-title":"Ferric ion-induced lipid peroxidation in erythrocyte membranes: Effects of phytic acid and butylated hydroxytoluene","volume":"95","author":"Ko","year":"1990","journal-title":"Mol. Cell. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1365-2621.1995.tb05646.x","article-title":"Phytic Acid Protective Effect Against Beef Round Muscle Lipid Peroxidation","volume":"60","author":"Lee","year":"1995","journal-title":"J. Food Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"del Mar Arriero, M., Ramis, J.M., Perell\u00f3, J., and Monjo, M. (2012). Inositol hexakisphosphate inhibits osteoclastogenesis on RAW 264.7 cells and human primary osteoclasts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043187"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1159\/000341474","article-title":"Differential response of MC3T3-E1 and human mesenchymal stem cells to inositol hexakisphosphate","volume":"30","author":"Ramis","year":"2012","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.bone.2010.01.367","article-title":"Inositol hexakisphosphate inhibits mineralization of MC3T3-E1 osteoblast cultures","volume":"46","author":"Addison","year":"2010","journal-title":"Bone"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111402","DOI":"10.1016\/j.msec.2020.111402","article-title":"Micro\/nanostructured calcium phytate coating on titanium fabricated by chemical conversion deposition for biomedical application","volume":"118","author":"Zhang","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11491","DOI":"10.1038\/s41598-019-48015-5","article-title":"Glycerylphytate compounds with tunable ion affinity and osteogenic properties","volume":"9","author":"Vilaboa","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116269","DOI":"10.1016\/j.carbpol.2020.116269","article-title":"Glycerylphytate crosslinker as a potential osteoinductor of chitosan-based systems for guided bone regeneration","volume":"241","author":"Barbosa","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.2741\/e167","article-title":"Phytate levels and bone parameters: A retrospective pilot clinical trial","volume":"2","author":"Grases","year":"2010","journal-title":"Front. Biosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1089\/jmf.2009.0152","article-title":"Effect of Tetracalcium Dimagnesium Phytate on Bone Characteristics in Ovariectomized Rats","volume":"13","author":"Grases","year":"2010","journal-title":"J. Med. Food."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/stem.646","article-title":"Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt\/catenin signaling","volume":"29","author":"Yang","year":"2011","journal-title":"Stem Cells"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1159\/000204105","article-title":"Strontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras\/MAPK signaling pathway","volume":"23","author":"Peng","year":"2009","journal-title":"Cell Physiol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1039\/C8TB02738B","article-title":"Bibliographic review on the state of the art of strontium and zinc based regenerative therapies. Recent developments and clinical applications","volume":"7","author":"Abradelo","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s12011-017-1119-7","article-title":"Zinc Metabolism and Metallothioneins","volume":"183","author":"Baltaci","year":"2018","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1359\/jbmr.1999.14.5.661","article-title":"Strontium and Bone","volume":"14","author":"Cabrera","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bone.2005.07.029","article-title":"Strontium ranelate: A physiological approach for optimizing bone formation and resorption","volume":"38","author":"Marie","year":"2006","journal-title":"Bone"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1039\/C4TB01969E","article-title":"The synthesis and characterisation of strontium and calcium folates with potential osteogenic activity","volume":"3","author":"Rojo","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1447S","DOI":"10.1093\/jn\/130.5.1447S","article-title":"The Antioxidant Properties of Zinc","volume":"130","author":"Powell","year":"2000","journal-title":"J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"356","DOI":"10.4162\/nrp.2010.4.5.356","article-title":"Zinc may increase bone formation through stimulating cell proliferation, alkaline phosphatase activity and collagen synthesis in osteoblastic MC3T3-E1 cells","volume":"4","author":"Seo","year":"2010","journal-title":"Nutr. Res. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"113152","DOI":"10.1016\/j.ejmech.2021.113152","article-title":"Vitamin B9 derivatives as carriers of bioactive cations for musculoskeletal regeneration applications: Synthesis, characterization and biological evaluation","volume":"212","author":"Asensio","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-Del-Campo, M., Sampedro, J.G., Flores-Cedillo, M.L., Rosales-Iba\u00f1ez, R., and Rojo, L. (2019). Bone regeneration induced by strontium folate loaded biohybrid scaffolds. Molecules, 24.","DOI":"10.3390\/molecules24091660"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1039\/C6BM00459H","article-title":"Strontium folate loaded biohybrid scaffolds seeded with dental pulp stem cells induce in vivo bone regeneration in critical sized defects","volume":"4","author":"Alvarado","year":"2016","journal-title":"Biomater. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Asensio, G., Benito-Garz\u00f3n, L., Ram\u00edrez-Jim\u00e9nez, R.A., Guadilla, Y., Gonzalez-Rubio, J., Abradelo, C., Parra, J., Mart\u00edn-L\u00f3pez, M.R., Aguilar, M.R., and V\u00e1zquez-Lasa, B. (2022). Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr\/Zn Folates for Osteochondral Tissue Engineering. Polymers, 14.","DOI":"10.3390\/polym14010012"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-022-24300-8","article-title":"A study on Sr\/Zn phytate complexes: Structural properties and antimicrobial synergistic effects against Streptococcus mutans","volume":"12","author":"Asensio","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1006\/abbi.1994.1485","article-title":"Action of Phenolic Derivatives (Acetaminophen)","volume":"315","author":"Dinis","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.spinee.2011.04.023","article-title":"A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: Emerging safety concerns and lessons learned","volume":"11","author":"Carragee","year":"2011","journal-title":"Spine J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00198-013-2582-4","article-title":"Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis: A nested case-control study in the CPRD","volume":"25","author":"Cooper","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00198-013-2469-4","article-title":"Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate","volume":"25","author":"Abrahamsen","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Milkovic, L., Gasparovic, A.C., Cindric, M., Mouthuy, P.-A., and Zarkovic, N. (2019). Short Overview of ROS as Cell Function Regulators and Their Implications in Therapy Concepts. Cells, 8.","DOI":"10.3390\/cells8080793"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0306-3623(96)00178-4","article-title":"Comparative in vitro oxygen radical scavenging ability of zinc methionine and selected zinc salts and antioxidants","volume":"28","author":"Bagchi","year":"1997","journal-title":"Gen. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fnut.2014.00014","article-title":"Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health","volume":"1","author":"Prasad","year":"2014","journal-title":"Front. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/ajcn\/57.5.715S","article-title":"Lipid peroxidation: Significance and its mechanism","volume":"57","author":"Halliwell","year":"1993","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1179\/135100002125000596","article-title":"Iron and carcinogenesis: From Fenton reaction to target genes","volume":"7","author":"Toyokuni","year":"2002","journal-title":"Redox Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jinorgbio.2004.12.011","article-title":"Solution behaviour of myo -inositol hexakisphosphate in the presence of multivalent cations. Prediction of a neutral pentamagnesium species under cytosolic\/nuclear conditions","volume":"99","author":"Torres","year":"2005","journal-title":"J. Inorg. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"82746","DOI":"10.3389\/fchem.2020.582746","article-title":"Complex Formation of Phytic Acid With Selected Monovalent and Divalent Metals","volume":"8","author":"Marolt","year":"2020","journal-title":"Front. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/jbmr.2974","article-title":"SOD2 and Sirt3 Control Osteoclastogenesis by Regulating Mitochondrial ROS","volume":"32","author":"Kim","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00774-015-0656-4","article-title":"Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases","volume":"33","author":"Callaway","year":"2015","journal-title":"J. Bone Miner. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s40097-018-0255-8","article-title":"Eco-friendly synthesis of metal nanoparticles using ginger and garlic extracts as biocompatible novel antioxidant and antimicrobial agents","volume":"8","author":"Ghoniem","year":"2018","journal-title":"J. Nanostructure Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s12011-019-01894-1","article-title":"Fabrication of Ultra-Pure Anisotropic Zinc Oxide Nanoparticles via Simple and Cost-Effective Route: Implications for UTI and EAC Medications","volume":"196","author":"Elkodous","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.enzmictec.2018.06.009","article-title":"Biosynthesis of zinc oxide nanoparticles usingMangifera indica leaves and evaluation of their antioxidant and cytotoxic properties in lung cancer (A549) cells","volume":"117","author":"Rajeshkumar","year":"2018","journal-title":"Enzym. Microb. Technol."},{"key":"ref_60","first-page":"217","article-title":"Novel conductive polypyrrole \/ zinc oxide\/chitosan bionanocomposite: Synthesis, characterization, antioxidant, and antibacterial activities","volume":"10","author":"Press","year":"2015","journal-title":"Int. J. Nanomedicine."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.foodchem.2012.10.118","article-title":"Antioxidant and antimicrobial activity of xylan-chitooligomer-zinc complex","volume":"138","author":"Wu","year":"2013","journal-title":"Food Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"863","DOI":"10.4028\/www.scientific.net\/AMR.183-185.863","article-title":"Study on antioxidant activity of dihydromyricetin-zinc(II) complex","volume":"183\u2013185","author":"Wu","year":"2011","journal-title":"Adv. Mater. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"65","DOI":"10.25135\/acg.oc.80.20.05.1639","article-title":"Synthesis of chalcone-containing zinc and cobalt metallophthalocyanines; investigation of their photochemical, DPPH radical scavenging and metal chelating characters","volume":"13","author":"Baran","year":"2020","journal-title":"Org. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0021-9150(94)90192-9","article-title":"Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL, and affects their secretory properties","volume":"111","author":"Fuhrman","year":"1994","journal-title":"Atherosclerosis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ab.2016.10.021","article-title":"Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges","volume":"524","author":"Tsikas","year":"2017","journal-title":"Anal. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3109\/10715769809065821","article-title":"Measurement of lipid peroxidation","volume":"28","author":"Moore","year":"1998","journal-title":"Free Radic. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Huntosova, V., Horvath, D., Seliga, R., and Wagnieres, G. (2021). Influence of oxidative stress on time-resolved oxygen detection by [ru(Phen)3 ]2+ in vivo and in vitro. Molecules, 26.","DOI":"10.3390\/molecules26020485"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bose, C., Hindle, A., Lee, J., Kopel, J., Tonk, S., Palade, P.T., Singhal, S.S., Awasthi, S., and Singh, S.P. (2021). Anticancer activity of \u03a9-6 fatty acids through increased 4-hne in breast cancer cells. Cancers, 13.","DOI":"10.3390\/cancers13246377"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1021\/acs.chemrestox.9b00378","article-title":"Mycotoxin Altertoxin II Induces Lipid Peroxidation Connecting Mitochondrial Stress Response to NF-\u03baB Inhibition in THP-1 Macrophages","volume":"33","author":"Hohenbichler","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/ajcn\/33.1.51","article-title":"Enhanced lipid peroxidation in liver microsomes of zinc-deficient rats","volume":"33","author":"Sullivan","year":"1980","journal-title":"Am J Clin Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1177\/0960327116666619","article-title":"Investigation of lipid peroxidation and antiapoptotic effects of zinc aganist liver damage in diabetic rats","volume":"36","year":"2017","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4067\/S0716-97602000000200014","article-title":"Zinc in the prevention of Fe2+-initiated lipid and protein oxidation","volume":"33","author":"Zago","year":"2000","journal-title":"Biol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/35073015","article-title":"Back in the water: The return of the inositol phosphate","volume":"2","author":"Irvine","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"111768","DOI":"10.1016\/j.colsurfb.2021.111768","article-title":"Covalent immobilization of the phytic acid-magnesium layer on titanium improves the osteogenic and antibacterial properties","volume":"203","author":"Liu","year":"2021","journal-title":"Colloids Surfaces B Biointerfaces."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.apsusc.2017.03.191","article-title":"Osteogenic potential of a novel microarc oxidized coating formed on Ti6Al4V alloys","volume":"412","author":"Wang","year":"2017","journal-title":"Appl. Surf. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.colsurfb.2018.05.057","article-title":"Universal and biocompatible hydroxyapatite coating induced by phytic acid-metal complex multilayer","volume":"169","author":"Wang","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1111\/iej.13505","article-title":"Regeneration of pulp-dentine complex-like tissue in a rat experimental model under an inflammatory microenvironment using high phosphorous-containing bioactive glasses","volume":"54","author":"Li","year":"2021","journal-title":"Int. Endod. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.bone.2007.08.043","article-title":"Dual effect of strontium ranelate: Stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro","volume":"42","author":"Bonnelye","year":"2008","journal-title":"Bone"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/j.actbio.2008.05.005","article-title":"Strontium-substituted hydroxyapatite coatings synthesized by pulsed-laser deposition: In vitro osteoblast and osteoclast response","volume":"4","author":"Capuccini","year":"2008","journal-title":"Acta Biomater."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1016\/j.actbio.2010.01.017","article-title":"Osteoblast response and osseointegration of a Ti-6Al-4V alloy implant incorporating strontium","volume":"6","author":"Park","year":"2010","journal-title":"Acta Biomater."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/339\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:10:33Z","timestamp":1760119833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":80,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["pharmaceutics15020339"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15020339","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]}}}