{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:33:51Z","timestamp":1740126831404,"version":"3.37.3"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"09","funder":[{"DOI":"10.13039\/501100002964","name":"\u00c7ukurova \u00dcniversitesi","doi-asserted-by":"crossref","award":["TSA-2021-13354"],"award-info":[{"award-number":["TSA-2021-13354"]}],"id":[{"id":"10.13039\/501100002964","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:p>\n            Objective\u2003Hydroxychloroquine (HCQ) has immunomodulatory, antithrombotic, cardiovascular, antimicrobial, and antineoplastic effects. In this study, we aimed to investigate the antiapoptotic and immunomodulator effects of intraperitoneal HCQ on hypoxic\u2013ischemic (HI) injury in newborn rats.<\/jats:p><jats:p>\n            Study Design\u2003Wistar albino rats, 7 to 10 days old, were randomly divided into three groups: hypoxic\u2013ischemic encephalopathy (HIE) group, HIE treated with HCQ group, and Sham group. Left common carotid artery ligation and hypoxia model were performed in HIE and HCQ groups. The HCQ group was treated with 80\u2009mg\/kg intraperitoneal HCQ every 24\u2009hours for 3 days, while Sham and HIE groups were given physiological saline. After 72\u2009hours, rats were decapitated and brain tissues were stained with hematoxylin and eosin, TUNEL, and IL-1\u03b2 for histopathological grading and neuronal cell injury.<\/jats:p><jats:p>\n            Results\u2003Neuronal apoptosis was statistically lower in all neuroanatomical areas in the HCQ group compared with the HIE group. IL-1\u03b2-stained areas were similar in both HCQ and HIE groups but significantly higher compared with the Sham group. Histopathological grading scores were found to be lower in the HCQ group on the left parietal cortex and hippocampus region.<\/jats:p><jats:p>\n            Conclusion\u2003In this study, we have shown for the first time that HCQ treatment decreased apoptosis in HI newborn rat model in both hemispheres. HCQ may be a promising adjuvant therapy in neonatal HIE.<\/jats:p><jats:p>\n            Key Points\n          <\/jats:p>","DOI":"10.1055\/a-1798-2003","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:11:12Z","timestamp":1647389472000},"page":"1195-1202","source":"Crossref","is-referenced-by-count":0,"title":["Antiapoptotic Effects of Hydroxychloroquine on Hypoxic\u2013Ischemic Injury in Neonatal Rat Brain: May Hydroxychloroquine Be an Adjuvant Theraphy?"],"prefix":"10.1055","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7926-8442","authenticated-orcid":false,"given":"Tugay","family":"Tepe","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Neonatology, Department of Pediatrics, Neonatology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5718-0503","authenticated-orcid":false,"given":"Mehmet","family":"Satar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Neonatology, Department of Pediatrics, Neonatology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-553X","authenticated-orcid":false,"given":"Hacer Yapicioglu","family":"Yildizdas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Neonatology, Department of Pediatrics, Neonatology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-8283","authenticated-orcid":false,"given":"Mustafa","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Neonatology, Department of Pediatrics, Neonatology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2092-8426","authenticated-orcid":false,"given":"Ferda","family":"Ozlu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Neonatology, Department of Pediatrics, Neonatology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyda","family":"Erdogan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pathology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tugba","family":"Toyran","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pathology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4896-8822","authenticated-orcid":false,"given":"Kubra","family":"Akillioglu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Neurophysiology, Department of Physiology, Cukurova University, Adana, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ejpn.2008.05.001","article-title":"A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy","volume":"13","author":"T W Pin","year":"2009","journal-title":"Eur J Paediatr Neurol"},{"issue":"12","key":"ref2","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1080\/14767058.2017.1321628","article-title":"Ante- and intrapartum risk factors for neonatal hypoxic ischemic encephalopathy","volume":"31","author":"C Lundgren","year":"2018","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa1315788","article-title":"Effects of hypothermia for perinatal asphyxia on childhood outcomes","volume":"371","author":"D Azzopardi","year":"2014","journal-title":"N Engl J Med"},{"issue":"11","key":"ref4","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1002\/art.11304","article-title":"Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group","volume":"48","author":"N Costedoat-Chalumeau","year":"2003","journal-title":"Arthritis Rheum"},{"issue":"03","key":"ref5","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1136\/ard.45.3.244","article-title":"Antioxidant action of antimalarials","volume":"45","author":"Y Miyachi","year":"1986","journal-title":"Ann Rheum Dis"},{"issue":"05","key":"ref6","first-page":"803","article-title":"Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells","volume":"20","author":"K Sperber","year":"1993","journal-title":"J Rheumatol"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"e2059","DOI":"10.1038\/cddis.2015.361","article-title":"Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis","volume":"7","author":"A Ruiz","year":"2016","journal-title":"Cell Death Dis"},{"issue":"09","key":"ref8","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1093\/rheumatology\/kev404","article-title":"BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids","volume":"55","author":"J Flint","year":"2016","journal-title":"Rheumatology (Oxford)"},{"issue":"06","key":"ref9","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/jp.2012.131","article-title":"Successful treatment of neonatal respiratory failure caused by a novel surfactant protein C p.Cys121Gly mutation with hydroxychloroquine","volume":"33","author":"N Hepping","year":"2013","journal-title":"J Perinatol"},{"issue":"03","key":"ref10","first-page":"E66","article-title":"SFTPC gene mutation p.R167Q in a premature infant","volume":"49","author":"C Jon","year":"2014","journal-title":"Pediatr Pulmonol"},{"issue":"01","key":"ref12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1177\/0976500X20120105","article-title":"The national centre for the replacement, refinement, and reduction of animals in research","volume":"3","author":"J Singh","year":"2012","journal-title":"J Pharmacol Pharmacother"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/ilar.47.1.5","article-title":"Design and statistical methods in studies using animal models of development","volume":"47","author":"M FW Festing","year":"2006","journal-title":"ILAR J"},{"issue":"02","key":"ref14","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"J E Rice III","year":"1981","journal-title":"Ann Neurol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1749-6632.1997.tb48634.x","article-title":"A model of perinatal hypoxic-ischemic brain damage","volume":"835","author":"R C Vannucci","year":"1997","journal-title":"Ann N Y Acad Sci"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jneumeth.2014.04.005","article-title":"Validation of a neuropathology score using quantitative methods to evaluate brain injury in a pig model of hypoxia ischaemia","volume":"230","author":"N Hoque","year":"2014","journal-title":"J Neurosci Methods"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbi.2017.08.002","article-title":"Systemic infusions of anti-interleukin-1\u03b2 neutralizing antibodies reduce short-term brain injury after cerebral ischemia in the ovine fetus","volume":"67","author":"X Chen","year":"2018","journal-title":"Brain Behav Immun"},{"issue":"05","key":"ref18","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.jpeds.2011.08.004","article-title":"Hypothermia and other treatment options for neonatal encephalopathy: an executive summary of the Eunice Kennedy Shriver NICHD workshop","volume":"159","author":"R D Higgins","year":"2011","journal-title":"J Pediatr"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"4901014","DOI":"10.1155\/2016\/4901014","article-title":"Plasticity in the neonatal brain following hypoxic-ischaemic injury","volume":"2016","author":"E Rocha-Ferreira","year":"2016","journal-title":"Neural Plast"},{"issue":"16","key":"ref20","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1001\/jama.2017.14972","article-title":"Effect of therapeutic hypothermia initiated after 6\u2009hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy a randomized clinical trial","volume":"318","author":"A R Laptook","year":"2017","journal-title":"JAMA"},{"issue":"01","key":"ref21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2017.7218","article-title":"Effect of depth and duration of cooling on death or disability at age 18 months among neonates with hypoxic-ischemic encephalopathy a randomized clinical trial","volume":"318","author":"S Shankaran","year":"2017","journal-title":"JAMA"},{"issue":"06","key":"ref22","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1203\/00006450-199412000-00003","article-title":"Delayed (\u201csecondary\u201d) cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy","volume":"36","author":"A Lorek","year":"1994","journal-title":"Pediatr Res"},{"issue":"02","key":"ref23","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S1474-4422(13)70261-8","article-title":"Mitochondria: hub of injury responses in the developing brain","volume":"13","author":"H Hagberg","year":"2014","journal-title":"Lancet Neurol"},{"issue":"21","key":"ref24","doi-asserted-by":"crossref","first-page":"7994","DOI":"10.1523\/JNEUROSCI.20-21-07994.2000","article-title":"Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat","volume":"20","author":"W Nakajima","year":"2000","journal-title":"J Neurosci"},{"issue":"06","key":"ref25","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1191\/096120301678646092","article-title":"Antimalarials\u2014the 'real' advance in lupus","volume":"10","author":"D J Wallace","year":"2001","journal-title":"Lupus"},{"issue":"03","key":"ref26","doi-asserted-by":"crossref","first-page":"e92673","DOI":"10.1371\/journal.pone.0092673","article-title":"Acute pretreatment with chloroquine attenuates renal I\/R injury in rats","volume":"9","author":"Z Todorovic","year":"2014","journal-title":"PLoS One"},{"issue":"06","key":"ref27","doi-asserted-by":"crossref","first-page":"e694","DOI":"10.1038\/cddis.2013.225","article-title":"Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase","volume":"4","author":"H Fang","year":"2013","journal-title":"Cell Death Dis"},{"issue":"07","key":"ref28","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1161\/STROKEAHA.107.504175","article-title":"Strong neuroprotection by inhibition of NF-kappaB after neonatal hypoxia-ischemia involves apoptotic mechanisms but is independent of cytokines","volume":"39","author":"C HA Nijboer","year":"2008","journal-title":"Stroke"},{"issue":"03","key":"ref29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41419-018-0378-3","article-title":"Hydroxychloroquine attenuates renal ischemia\/reperfusion injury by inhibiting cathepsin mediated NLRP3 inflammasome activation","volume":"9","author":"T T Tang","year":"2018","journal-title":"Cell Death Dis"},{"issue":"03","key":"ref30","doi-asserted-by":"crossref","first-page":"F190","DOI":"10.1136\/fn.79.3.F190","article-title":"Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-\u03b1 and interleukin-1 \u03b2 concentrations on outcome of full term infants with hypoxic-ischaemic encephalopathy","volume":"79","author":"N Oyg\u00fcr","year":"1998","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jns.2015.08.1525","article-title":"Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis","volume":"358","author":"M W Koch","year":"2015","journal-title":"J Neurol Sci"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.neuroscience.2012.01.008","article-title":"Reduced infarct size and accumulation of microglia in rats treated with WIN 55,212-2 after neonatal stroke","volume":"207","author":"D Fern\u00e1ndez-L\u00f3pez","year":"2012","journal-title":"Neuroscience"},{"issue":"09","key":"ref33","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/sj.jcbfm.9600121","article-title":"Minocycline confers early but transient protection in the immature brain following focal cerebral ischemia-reperfusion","volume":"25","author":"C Fox","year":"2005","journal-title":"J Cereb Blood Flow Metab"},{"issue":"06","key":"ref34","doi-asserted-by":"crossref","first-page":"766","DOI":"10.6061\/clinics\/2013(06)07","article-title":"Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients","volume":"68","author":"J C Silva","year":"2013","journal-title":"Clinics (S\u00e3o Paulo)"},{"issue":"13","key":"ref35","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1177\/0961203315591027","article-title":"Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study","volume":"24","author":"M Leroux","year":"2015","journal-title":"Lupus"},{"issue":"07","key":"ref36","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.7150\/ijms.34141","article-title":"Torsades de pointes and QT prolongation Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System","volume":"16","author":"C Teng","year":"2019","journal-title":"Int J Med Sci"},{"issue":"09","key":"ref37","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1177\/0961203318787040","article-title":"Hydroxychloroquine: an update","volume":"27","author":"G Hughes","year":"2018","journal-title":"Lupus"},{"issue":"03","key":"ref38","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"S Reagan-Shaw","year":"2008","journal-title":"FASEB J"}],"container-title":["American Journal of Perinatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1798-2003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T16:44:07Z","timestamp":1730825047000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1798-2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,15]]},"references-count":37,"journal-issue":{"issue":"09","published-online":{"date-parts":[[2024,6,18]]},"published-print":{"date-parts":[[2024,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1798-2003","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0735-1631","1098-8785"],"issn-type":[{"type":"print","value":"0735-1631"},{"type":"electronic","value":"1098-8785"}],"subject":[],"published-other":{"date-parts":[[2022,3,15]]},"published":{"date-parts":[[2022,3,15]]}}}