{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:53:49Z","timestamp":1773312829840,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T00:00:00Z","timestamp":1485129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>Implicated in influenza\u2010associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue\u2010sensitive antimicrobial agents. At different time points, mice were pre\u2010treated with kolaviron (400 mg\/kg), a natural antioxidant and anti\u2010inflammatory agent, and subsequently challenged with 2 <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content><jats:sub>50<\/jats:sub> influenza A\/H3N2\/Perth\/16\/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo\u2010inflammatory imbalance, cytokine storm indices and T helper 1 host response. Previously kolaviron was reported to delay mortality onset, improve morbidity and attenuate myeloperoxidase activity and nitric oxide production with minimal impact on viral clearance. This study additionally confirmed nitric oxide, but not hydrogen peroxide, as the major culprit implicated in influenza virus\u2010induced oxido\u2010pathology. Systemic effect of the sustained inflammation and nitrosative stress was more prominent in the spleen and lung than in the liver of mice infected with A\/H3N2\/Perth\/16\/09. Influential to immunopathology was heightened pulmonary expression of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2, <jats:styled-content style=\"fixed-case\">RANTES<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> IL<\/jats:styled-content>\u201010, <jats:styled-content style=\"fixed-case\">MCP<\/jats:styled-content>\u20101, <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB, <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102. However, kolaviron combated the influenza\u2010established nitrative stress, reversed the elicited cytokine storm and restored the oxidized environment to a reductive milieu. Our data also suggest that kolaviron administration early in infection may foster CD4<jats:sup>+<\/jats:sup> response. These data indicate that kolaviron may confer disease\u2010dwindling properties during acute influenza infection via a system\u2010wide protective approach involving multiple targets especially at the early stage of the infection.<\/jats:p>","DOI":"10.1111\/apm.12640","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T03:56:41Z","timestamp":1485230201000},"page":"184-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mechanistic perspective of the oxido\u2010immunopathologic resolution property of kolaviron in mice influenza pneumonitis"],"prefix":"10.1111","volume":"125","author":[{"given":"Ifeoluwa O.","family":"Awogbindin","sequence":"first","affiliation":[{"name":"Departments of Biochemistry University of Ibadan Ibadan Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David O.","family":"Olaleye","sequence":"additional","affiliation":[{"name":"Department of Virology University of Ibadan Ibadan Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebenezer O.","family":"Farombi","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry University of Ibadan Ibadan Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2012.05.005"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100026"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.06.003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr0805865"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0235623100"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2448"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.8.1541"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-10-104"},{"key":"e_1_2_7_10_1","first-page":"501","article-title":"Using complementary and alternative medicines to target the host response during severe influenza","volume":"7","author":"Alleva LM","year":"2010","journal-title":"eCAM"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.09.008"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711942105"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812689106"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2014.966082"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-8741(87)90123-1"},{"key":"e_1_2_7_16_1","volume-title":"Traditional Igbo Medicine","author":"Iwu MM","year":"1982"},{"key":"e_1_2_7_17_1","first-page":"238","article-title":"A novel biflavonoids from the roots of Garcinia kola","volume":"50","author":"Terashima K","year":"1995","journal-title":"Heterocycles"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/13880209.2014.937504"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0305-1870.2005.04248.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2008.0138"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2008.11.012"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph8062533"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.5897\/AJB2003.000-1122"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2015.0013"},{"key":"e_1_2_7_25_1","first-page":"493","article-title":"A simple method for estimating fifty percent endpoints","volume":"27","author":"Reed LJ","year":"1938","journal-title":"Am J Hyg"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12506462"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.12.1537"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1017"},{"key":"e_1_2_7_29_1","first-page":"1113","article-title":"Acute hemolytic anaemia in the newborn infant due to naphthalene poisoning: report of two cases with investigations into the mechanism of the disease","volume":"13","author":"Dawson JP","year":"1958","journal-title":"Hematology"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000136485"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553009014552121"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)45228-9"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(94)33021-2"},{"key":"e_1_2_7_35_1","first-page":"273","volume-title":"Methods in Enzymology","author":"Motchnik AP","year":"1994"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.03.003"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107966"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X10366368"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu6020517"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070060"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(03)00023-6"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0508fje"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705289104"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.9.3996-4003.2000"},{"key":"e_1_2_7_45_1","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1128\/jvi.70.7.4411-4418.1996","article-title":"In vivo blockade of gamma interferon affects the influenza virus\u2010 induced humoral and the local cellular immune response in lung tissue","volume":"70","author":"Baumgarth N","year":"1996","journal-title":"J Virol"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.150318"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/v4123363"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710791299957"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211798357728"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-135590"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.2174\/1876518101002020034"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules16032032"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568010054526359"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.1.L69"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000196"},{"key":"e_1_2_7_56_1","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1128\/jvi.69.3.1480-1484.1995","article-title":"Expression of influenza virus hemagglutinin activates transcription factor NF\u2010kappa B","volume":"69","author":"Baeuerle PA","year":"1995","journal-title":"J Virol"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00280.2001"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042419"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101050"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900657"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2004.02.004"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.07172-11"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63689"}],"container-title":["APMIS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapm.12640","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apm.12640","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T01:10:12Z","timestamp":1695517812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apm.12640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,23]]},"references-count":62,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1111\/apm.12640"],"URL":"https:\/\/doi.org\/10.1111\/apm.12640","archive":["Portico"],"relation":{},"ISSN":["0903-4641","1600-0463"],"issn-type":[{"value":"0903-4641","type":"print"},{"value":"1600-0463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,23]]},"assertion":[{"value":"2016-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}