{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T03:16:56Z","timestamp":1768619816033,"version":"3.49.0"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Center for Animal Biologics","award":["MOST 109-2634-F-020-001, MOST 110-2634-F-020-001"],"award-info":[{"award-number":["MOST 109-2634-F-020-001, MOST 110-2634-F-020-001"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>This study aimed to assess the in vitro antimicrobial effects of chlorhexidine (CHX) and povidone-iodine (PI) on clinical isolates of <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic>) and <jats:italic>Trueperella pyogenes<\/jats:italic> (<jats:italic>T<\/jats:italic>. <jats:italic>pyogenes<\/jats:italic>) from the vaginal discharge of dairy cows, as well as to compare the cytotoxicity effects of CHX and PI on bovine endometrial epithelial cells (BEnEpC). In Experiment 1, 12 <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and 10 <jats:italic>T<\/jats:italic>. <jats:italic>pyogenes<\/jats:italic> were isolated from the vaginal discharge of cows with a uterine infection. The MIC and MBC against CHX and PI were analyzed in vitro. In Experiment 2, the cytotoxicity effects of CHX and PI on BEnEpC were analyzed using a Viability\/Cytotoxicity Kit, wound scratch healing assay, and the expression of pro-inflammatory cytokine genes (IL-6, IL-8, and TNF-\u03b1). In Experiment 1, the MIC and MBC values of CHX against <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> were 0.0002% and 0.0002 to 0.00025%, respectively. The MIC and MBC values of PI were 1.25 to 2.5% and 1.25 to 5%, respectively. For <jats:italic>T<\/jats:italic>. <jats:italic>pyogenes<\/jats:italic>, the MIC and MBC values of CHX were 0.00002%. The MIC and MBC values of PI were 1.25%. In Experiment 2, the cell viability significantly decreased, and wound closures were significantly inhibited after treatment with \u2265 0.002% CHX and \u2265 0.025% PI. The expression of IL-6, IL-8, and TNF-\u03b1 significantly increased after treatment with PI. Only IL-6 showed a significant increase after cells were treated with 0.00002% and 0.0002% CHX. The results suggested that both CHX and PI had high antibacterial effects. However, veterinarians and farmers should be aware of their cytotoxicity, which decrease viability of endometrial epithelial cells and inhibit wound healing in vitro.<\/jats:p>","DOI":"10.1371\/journal.pone.0271274","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T17:58:59Z","timestamp":1657303139000},"page":"e0271274","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["An in vitro comparison of antimicrobial efficacy and cytotoxicity between povidone-iodine and chlorhexidine for treating clinical endometritis in dairy cows"],"prefix":"10.1371","volume":"17","author":[{"given":"Natcha","family":"Thongrueang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyh-Shyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan-Yu","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9651-6831","authenticated-orcid":true,"given":"Hsu-Hsun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"issue":"6","key":"pone.0271274.ref001","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1095\/biolreprod.109.077370","article-title":"Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle","volume":"81","author":"IM Sheldon","year":"2009","journal-title":"Biol Reprod"},{"issue":"6","key":"pone.0271274.ref002","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1530\/rep.0.1230837","article-title":"Influence of uterine bacterial contamination after parturition on ovarian dominant follicle selection and follicle growth and function in cattle","volume":"123","author":"IM Sheldon","year":"2002","journal-title":"Reprod"},{"issue":"4","key":"pone.0271274.ref003","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.theriogenology.2007.04.056","article-title":"The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow","volume":"68","author":"EJ Williams","year":"2007","journal-title":"Theriogenology"},{"issue":"9","key":"pone.0271274.ref004","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.3168\/jds.S0022-0302(02)74302-6","article-title":"Defining and diagnosing postpartum clinical endometritis and its impact on reproductive performance in dairy cows","volume":"85","author":"SJ LeBlanc","year":"2002","journal-title":"J Dairy Sci"},{"issue":"9","key":"pone.0271274.ref005","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1016\/j.theriogenology.2014.08.018","article-title":"Dynamics of bacteriologic and cytologic changes in the uterus of postpartum dairy cows","volume":"82","author":"I Prunner","year":"2014","journal-title":"Theriogenology"},{"issue":"1","key":"pone.0271274.ref006","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.theriogenology.2004.03.017","article-title":"Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle","volume":"63","author":"EJ Williams","year":"2005","journal-title":"Theriogenology"},{"issue":"5","key":"pone.0271274.ref007","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1439-0531.1997.tb01291.x","article-title":"Effect of intrauterine infusion of polyvinylpyrrolidone iodine and intramuscular injection of prostaglandin F2\u03b1 on reproductive performance in cows","volume":"32","author":"S Ohtani","year":"1997","journal-title":"Reprod Domest Anim"},{"key":"pone.0271274.ref008","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3906\/vet-1703-74","article-title":"The application of EDTA-Tris and chlorhexidine in the treatment of endometritis as a replacement for antibiotic therapy in cows","volume":"42","author":"I Stojanov","year":"2018","journal-title":"Turk J Vet Anim Sci"},{"issue":"7","key":"pone.0271274.ref009","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1292\/jvms.20-0165","article-title":"Intrauterine infusion of povidone-iodine: Its effect on the endometrium and subsequent fertility in postpartum dairy cows","volume":"82","author":"R Yoshida","year":"2020","journal-title":"J Vet Med Sci"},{"issue":"5","key":"pone.0271274.ref010","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1046\/j.1439-0531.2001.00290.x","article-title":"Combined gnRH and PGF2alpha application in cows with endometritis puerperalis treated with antibiotics","volume":"36","author":"T Janowski","year":"2001","journal-title":"Reprod Domest Anim"},{"issue":"21","key":"pone.0271274.ref011","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/vr.142.21.575","article-title":"Comparison of three treatments for bovine endometritis","volume":"142","author":"IM Sheldon","year":"1998","journal-title":"Vet Rec"},{"issue":"1\u20132","key":"pone.0271274.ref012","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.anireprosci.2003.08.010","article-title":"Effect of intrauterine administration of oestradiol on postpartum uterine bacterial infection in cattle","volume":"81","author":"IM Sheldon","year":"2004","journal-title":"Anim Reprod Sci"},{"issue":"1","key":"pone.0271274.ref013","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4315\/0362-028X-40.1.57","article-title":"Hormonal substances in human milk, cow\u2019s milk and dairy products","volume":"40","author":"T Richardson","year":"1977","journal-title":"J Food Prot"},{"issue":"17","key":"pone.0271274.ref014","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1136\/vr.161.17.585","article-title":"Persistence of oxytetracycline residues in milk after the intrauterine treatment of lactating cows for endometritis","volume":"161","author":"X Tan","year":"2007","journal-title":"Vet Rec"},{"key":"pone.0271274.ref015","first-page":"121","article-title":"Iodine in milk and serum following intrauterine infusion of Lugol\u2019s solution","volume":"6","author":"C Carleton","year":"2008","journal-title":"International Journal of Applied Research in Veterinary Medicine"},{"issue":"6","key":"pone.0271274.ref016","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/0093-691X(92)90186-U","article-title":"A histological study of the effect of saline and povidone-iodine infusions on the equine endometrium","volume":"37","author":"LM Olsen","year":"1992","journal-title":"Theriogenology"},{"issue":"3","key":"pone.0271274.ref017","doi-asserted-by":"crossref","first-page":"313","DOI":"10.4103\/njcp.njcp_253_20","article-title":"Comparative evaluation of the cytotoxic effects of different oral antiseptics: A primary culture study","volume":"24","author":"NZ Alpaslan Yayli","year":"2021","journal-title":"Niger J Clin Pract"},{"issue":"1","key":"pone.0271274.ref018","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/jp.2011.148","article-title":"Safety of chlorhexidine gluconate used for skin antisepsis in the preterm infant","volume":"32","author":"AK Chapman","year":"2012","journal-title":"J Perinatol"},{"issue":"4","key":"pone.0271274.ref019","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhin.2018.11.012","article-title":"Antiseptic efficacies of waterless hand rub, chlorhexidine scrub, and povidone-iodine scrub in surgical settings: a meta-analysis of randomized controlled trials","volume":"101","author":"YH Ho","year":"2019","journal-title":"J Hosp Infect"},{"issue":"6","key":"pone.0271274.ref020","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1136\/vr.105.6.122","article-title":"The irritancy of chlorhexidine gluconate in the genital tract of the mare","volume":"105","author":"PS Jackson","year":"1979","journal-title":"Vet Rec"},{"issue":"8","key":"pone.0271274.ref021","doi-asserted-by":"crossref","first-page":"e44285","DOI":"10.1371\/journal.pone.0044285","article-title":"Stromal-to-epithelial transition during postpartum endometrial regeneration","volume":"7","author":"CC Huang","year":"2012","journal-title":"PLoS One"},{"issue":"2","key":"pone.0271274.ref022","doi-asserted-by":"crossref","first-page":"217","DOI":"10.33073\/pjm-2019-022","article-title":"Campylobacter fetus is internalized by bovine endometrial epithelial cells","volume":"68","author":"LG Campos-M\u00fazquiz","year":"2019","journal-title":"Pol J Microbiol"},{"issue":"3","key":"pone.0271274.ref023","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/biolre\/ioaa226","article-title":"Conceptus-induced, interferon tau-dependent gene expression in bovine endometrial epithelial and stromal cells","volume":"104","author":"HL Chaney","year":"2021","journal-title":"Biol Reprod"},{"issue":"5","key":"pone.0271274.ref024","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1093\/humupd\/4.5.605","article-title":"Bovine endometrial epithelial cells as a model system to study oxytocin receptor regulation","volume":"4","author":"S Horn","year":"1998","journal-title":"Hum Reprod Update"},{"issue":"5","key":"pone.0271274.ref025","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/biolre\/ioab143","article-title":"Heat stress induces oxidative stress and activates the KEAP1-NFE2L2-ARE pathway in bovine endometrial epithelial cells","volume":"105","author":"H Murata","year":"2021","journal-title":"Biol Reprod"},{"issue":"22","key":"pone.0271274.ref026","doi-asserted-by":"crossref","first-page":"e14640","DOI":"10.14814\/phy2.14640","article-title":"Alteration of chemokine production in bovine endometrial epithelial and stromal cells under heat stress conditions","volume":"8","author":"S Sakai","year":"2020","journal-title":"Physiol Rep"},{"issue":"1","key":"pone.0271274.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08941939.2014.941445","article-title":"Cytokine expression in human osteoblasts after antiseptic treatment: A comparative study between polyhexanide and chlorhexidine","volume":"28","author":"E R\u00f6hner","year":"2015","journal-title":"J Invest Surg"},{"issue":"3","key":"pone.0271274.ref028","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3109\/01480545.2013.846364","article-title":"Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue","volume":"37","author":"S Sato","year":"2014","journal-title":"Drug Chem Toxicol"},{"key":"pone.0271274.ref029","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.tiv.2018.09.009","article-title":"A comparative study of skin irritation caused by novel bis-quaternary ammonium compounds and commonly used antiseptics by using cell culture methods","volume":"54","author":"M Yamamoto","year":"2019","journal-title":"Toxicol In Vitro"},{"issue":"6","key":"pone.0271274.ref030","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/ejcts\/ezt534","article-title":"Antineoplastic activity of povidone-iodine on different mesothelioma cell lines: results of in vitro study","volume":"45","author":"A Fiorelli","year":"2014","journal-title":"Eur J Cardiothorac Surg"},{"issue":"2","key":"pone.0271274.ref031","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.tiv.2007.09.012","article-title":"Effect of chlorhexidine digluconate on different cell types: a molecular and ultrastructural investigation","volume":"22","author":"M Giannelli","year":"2008","journal-title":"Toxicol In Vitro"},{"issue":"1","key":"pone.0271274.ref032","doi-asserted-by":"crossref","first-page":"16192","DOI":"10.1038\/s41598-020-73055-7","article-title":"An on-chip wound healing assay fabricated by xurography for evaluation of dermal fibroblast cell migration and wound closure","volume":"10","author":"G Shabestani Monfared","year":"2020","journal-title":"Scientific Reports"},{"issue":"4","key":"pone.0271274.ref033","doi-asserted-by":"crossref","first-page":"165","DOI":"10.7150\/jbji.26355","article-title":"Cytotoxicity evaluation of chlorhexidine gluconate on human fibroblasts, myoblasts, and osteoblasts","volume":"3","author":"JX Liu","year":"2018","journal-title":"J Bone Jt Infect"},{"issue":"23","key":"pone.0271274.ref034","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1097\/BRS.0000000000002224","article-title":"Povidone-iodine solutions inhibit cell migration and survival of osteoblasts, fibroblasts, and myoblasts","volume":"42","author":"JX Liu","year":"2017","journal-title":"Spine (Phila Pa 1976)"},{"key":"pone.0271274.ref035","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1477-7827-8-152","article-title":"Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum","volume":"8","author":"C Gabler","year":"2010","journal-title":"Reprod Biol Endocrinol"},{"issue":"8","key":"pone.0271274.ref036","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.theriogenology.2005.08.021","article-title":"Defining postpartum uterine disease in cattle","volume":"65","author":"IM Sheldon","year":"2006","journal-title":"Theriogenology"},{"issue":"1","key":"pone.0271274.ref037","doi-asserted-by":"crossref","first-page":"e0200974","DOI":"10.1371\/journal.pone.0200974","article-title":"Delayed differentiation of vaginal and uterine microbiomes in dairy cows developing postpartum endometritis","volume":"14","author":"R Miranda-CasoLuengo","year":"2019","journal-title":"PLoS One"},{"issue":"4","key":"pone.0271274.ref038","doi-asserted-by":"crossref","first-page":"e0154389","DOI":"10.1371\/journal.pone.0154389","article-title":"Comparison of boiling and robotics automation method in DNA extraction for metagenomic sequencing of human oral microbes","volume":"11","author":"J Yamagishi","year":"2016","journal-title":"PLOS ONE"},{"issue":"1","key":"pone.0271274.ref039","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1086\/315217","article-title":"Extended virulence genotypes of Escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise","volume":"181","author":"JR Johnson","year":"2000","journal-title":"J Infect Dis"},{"issue":"2","key":"pone.0271274.ref040","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/104063870201400212","article-title":"Isolation of Arcanobacterium (Actinomyces) pyogenes from cases of feline otitis externa and canine cystitis","volume":"14","author":"SJ Billington","year":"2002","journal-title":"J Vet Diagn Invest"},{"issue":"1\u20132","key":"pone.0271274.ref041","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.vetmic.2011.11.034","article-title":"Association between virulence factors of Escherichia coli, Fusobacterium necrophorum, and Arcanobacterium pyogenes and uterine diseases of dairy cows","volume":"157","author":"ML Bicalho","year":"2012","journal-title":"Vet Microbiol"},{"issue":"12","key":"pone.0271274.ref042","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.3168\/jds.2010-3550","article-title":"Molecular and epidemiological characterization of bovine intrauterine Escherichia coli","volume":"93","author":"RC Bicalho","year":"2010","journal-title":"J Dairy Sci"},{"issue":"1","key":"pone.0271274.ref043","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.mimet.2005.04.007","article-title":"Use of a spectrophotometric bioassay for determination of microbial sensitivity to manuka honey","volume":"64","author":"T Patton","year":"2006","journal-title":"J Microbiol Methods"},{"key":"pone.0271274.ref044","unstructured":"Institute CaLS. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard\u2014Ninth Edition. Broth Microdilution Method2012."},{"key":"pone.0271274.ref045","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.theriogenology.2018.12.011","article-title":"Characterization of cytokine gene expression in uterine cytobrush samples of non-endometritic versus endometritic postpartum dairy cows","volume":"126","author":"D Dadarwal","year":"2019","journal-title":"Theriogenology"},{"issue":"6","key":"pone.0271274.ref046","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.theriogenology.2014.12.007","article-title":"Early embryonic and endometrial regulation of tumor necrosis factor and tumor necrosis factor receptor 2 in the cattle uterus","volume":"83","author":"E Correia-\u00c1lvarez","year":"2015","journal-title":"Theriogenology"},{"issue":"8","key":"pone.0271274.ref047","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/0093-691X(95)00123-P","article-title":"The relationship between bacteriological and clinical findings in cows with subacute\/chronic endometritis","volume":"43","author":"MJW Dohmen","year":"1995","journal-title":"Theriogenology"},{"issue":"4","key":"pone.0271274.ref048","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1292\/jvms.15-0412","article-title":"Effects of intrauterine infusion of povidone-iodine on endometrial cytology and bacteriology in dairy cows with clinical endometritis","volume":"78","author":"S Mido","year":"2016","journal-title":"J Vet Med Sci"},{"key":"pone.0271274.ref049","doi-asserted-by":"crossref","first-page":"579","DOI":"10.2217\/cpr.13.50","article-title":"Antiseptics in the era of bacterial resistance: A focus on povidone iodine","volume":"10","author":"J-M Lachapelle","year":"2013","journal-title":"Clinical Practice"},{"issue":"2","key":"pone.0271274.ref050","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1556\/avet.2011.004","article-title":"Strategy for the treatment of puerperal metritis and improvement of reproductive efficiency in cows with retained placenta","volume":"59","author":"WB Liu","year":"2011","journal-title":"Acta Vet Hung"},{"issue":"6","key":"pone.0271274.ref051","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/0093-691X(88)90277-4","article-title":"Effect of postpartum intrauterine treatment with 2% polyvinyl-pyrrolidone-iodine solution on reproductive efficiency in cows","volume":"30","author":"T Nakao","year":"1988","journal-title":"Theriogenology"},{"issue":"3","key":"pone.0271274.ref052","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jhin.2016.08.018","article-title":"Acquired resistance to chlorhexidine\u2014is it time to establish an \u2019antiseptic stewardship\u2019 initiative?","volume":"94","author":"G. Kampf","year":"2016","journal-title":"J Hosp Infect"},{"issue":"2","key":"pone.0271274.ref053","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1053\/jhin.2002.1204","article-title":"Antibiotic resistance as an indicator of bacterial chlorhexidine susceptibility","volume":"51","author":"S K\u00f5ljalg","year":"2002","journal-title":"J Hosp Infect"},{"key":"pone.0271274.ref054","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.theriogenology.2017.08.010","article-title":"Mucosal immunity of the postpartum bovine genital tract","volume":"104","author":"D Dadarwal","year":"2017","journal-title":"Theriogenology"},{"issue":"2","key":"pone.0271274.ref055","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.taap.2008.10.012","article-title":"Chlorhexidine-induced apoptosis or necrosis in L929 fibroblasts: A role for endoplasmic reticulum stress","volume":"234","author":"G Faria","year":"2009","journal-title":"Toxicol Appl Pharmacol"},{"issue":"4","key":"pone.0271274.ref056","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0195-6701(91)90273-B","article-title":"Assay of antiseptic agents in cell culture: conditions affecting cytotoxicity","volume":"17","author":"FM Tatnall","year":"1991","journal-title":"J Hosp Infect"},{"issue":"4","key":"pone.0271274.ref057","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2106\/JBJS.M.00313","article-title":"Selection of an optimal antiseptic solution for intraoperative irrigation: an in vitro study","volume":"96","author":"SJ van Meurs","year":"2014","journal-title":"J Bone Joint Surg Am"},{"issue":"66","key":"pone.0271274.ref058","doi-asserted-by":"crossref","first-page":"53240","DOI":"10.1039\/C5RA08958A","article-title":"Limitations of MTT and CCK-8 assay for evaluation of graphene cytotoxicity","volume":"5","author":"G Jiao","year":"2015","journal-title":"RSC Advances"},{"issue":"4\u20135","key":"pone.0271274.ref059","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0887-2333(01)00020-0","article-title":"Mechanisms underlying chlorhexidine-induced cytotoxicity","volume":"15","author":"E Hidalgo","year":"2001","journal-title":"Toxicol In Vitro"},{"issue":"4","key":"pone.0271274.ref060","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1902\/jop.1977.48.4.212","article-title":"Cytopathologic effects of chlorhexidine on human cells","volume":"48","author":"P Goldschmidt","year":"1977","journal-title":"J Periodontol"},{"key":"pone.0271274.ref061","doi-asserted-by":"crossref","unstructured":"Lyday P, Kaiho T. Iodine and Iodine Compounds. 2015.","DOI":"10.1002\/14356007.a14_381.pub2"},{"issue":"5","key":"pone.0271274.ref062","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1007\/s10067-005-0133-x","article-title":"Toxic effects of povidone-iodine on synovial cell and articular cartilage","volume":"25","author":"M Kataoka","year":"2006","journal-title":"Clin Rheumatol"},{"issue":"2","key":"pone.0271274.ref063","first-page":"383","article-title":"Diluted povidone-iodine inhibits tumor growth through apoptosis-induction and suppression of SOD activity","volume":"27","author":"P Sun","year":"2012","journal-title":"Oncol Rep"},{"issue":"2","key":"pone.0271274.ref064","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1136\/bjo.2010.189407","article-title":"Povidone-iodine application induces corneal cell death through fixation","volume":"95","author":"SF Chou","year":"2011","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"pone.0271274.ref065","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/icvts\/ivy248","article-title":"Povidone-iodine results in rapid killing of thymic epithelial tumour cells through cellular fixation","volume":"28","author":"HS Lee","year":"2019","journal-title":"Interact Cardiovasc Thorac Surg"},{"issue":"1","key":"pone.0271274.ref066","doi-asserted-by":"crossref","first-page":"e13249","DOI":"10.1111\/aji.13249","article-title":"Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer\u2014Methodological considerations on the choice of analytical method for cytokine analyses","volume":"84","author":"P Israelsson","year":"2020","journal-title":"Am J Reprod Immunol"},{"issue":"6","key":"pone.0271274.ref067","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1128\/CDLI.7.6.920-924.2000","article-title":"Measurement of cytokine secretion, intracellular protein expression, and mRNA in resting and stimulated peripheral blood mononuclear cells","volume":"7","author":"KE Sullivan","year":"2000","journal-title":"Clin Diagn Lab Immunol"},{"issue":"1","key":"pone.0271274.ref068","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/CMR.12.1.147","article-title":"Antiseptics and disinfectants: activity, action, and resistance","volume":"12","author":"G McDonnell","year":"1999","journal-title":"Clinical microbiology reviews"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0271274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T18:00:07Z","timestamp":1657303207000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0271274"}},"subtitle":[],"editor":[{"given":"Peter J.","family":"Hansen","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,8]]},"references-count":68,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0271274","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,8]]}}}