{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:25Z","timestamp":1786978345000,"version":"build-2736575974"},"reference-count":67,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,7,9]],"date-time":"2023-07-09T00:00:00Z","timestamp":1688860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF 2012\u201040075\u2010C02\u201001"],"award-info":[{"award-number":["SAF 2012\u201040075\u2010C02\u201001"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cisplatin is clinically proven to combat different cancers, including sarcomas, soft tissue cancers, bones, muscles, and blood. However, renal and cardiovascular toxicities are important limitations in cisplatin therapeutical use. Immunoinflammation could be key factor in cisplatin\u2010induced toxicity. The aim of the present study was to evaluate the activation of the inflammatory TLR4\/NLRP3 pathway as a common mechanism for cardiovascular and renal cisplatin's cycles treatment toxicity. Adult male Wistar rats were treated with saline, cisplatin 2\u2009mg\/kg or cisplatin 3\u2009mg\/kg (intraperitoneally once a week, for five experimental weeks). After treatments, plasma, cardiac, vascular, and renal tissues were collected. Plasma malondialdehyde (MDA) and inflammatory cytokines were determined. TLR4, MyD88, NF\u2010\u03ba\u03b2 p65, NLRP3, and procaspase\u20101 tissue expressions were also analyzed. Cisplatin treatment induced a dose\u2010dependent increase in plasma MDA and IL\u201018. In cardiovascular system, an increase in NLRP3 and in cleaved caspase\u20101 were observed in cardiac tissue and a moderate increase in TLR4, MyD88 appeared in mesenteric artery. In kidney, a significant dose\u2010dependent increase in TLR4, MyD88 and NLRP3 and cleaved caspase 1 expressions were observed after cisplatin treatments. In conclusion, cisplatin cycles provoke a low grade pro\u2010inflammatory systemic state. Kidney was more sensitive than cardiovascular tissues to this pro\u2010inflammatory state. TLR4 and NLRP3 are key pathways involved in renal tissue damage, NLRP3 is the main pathway involved in cardiac toxicity and TLR4 pathway in resistance vessel toxicity.<\/jats:p>","DOI":"10.1002\/prp2.1108","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T01:31:00Z","timestamp":1688952660000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cisplatin cycles treatment sustains cardiovascular and renal damage involving TLR4 and NLRP3 pathways"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-3704","authenticated-orcid":false,"given":"Antonio","family":"Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC) Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom\u2010URJC), URJC  Alcorc\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad","family":"Garc\u00eda\u2010G\u00f3mez\u2010Heras","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom\u2010URJC), URJC  Alcorc\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Franco\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1378-0387","authenticated-orcid":false,"given":"Visitaci\u00f3n","family":"L\u00f3pez\u2010Miranda","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC) Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom\u2010URJC), URJC  Alcorc\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-6283","authenticated-orcid":false,"given":"Esperanza","family":"Herrad\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC) Universidad Rey Juan Carlos  Alcorc\u00f3n Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom\u2010URJC), URJC  Alcorc\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.07.025"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ACTHIS.2019.04.013"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CBI.2018.05.003"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01419"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.5617"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.04.009"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2016.10.001"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.08.126"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1502"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.05.034"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.07.053"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.932948"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHARMTHERA.2015.12.005"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9874109"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107511"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00196"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.17226\/12910"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00003-7"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2005.11.017"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.115287"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.7572"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20452"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15541"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2015.12.023"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/967826"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/EUROPACE\/EUP300"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.7852"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.5669"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.14694\/EDBOOK_AM.2012.32.40"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2459\/JCM.0000000000000376"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20123011"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1301"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-3132-8"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.2478\/acph-2020-0033"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7912763"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-017-1023-9"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25610-6"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.LFS.2020.118503"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.SJBS.2021.10.024"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13020-022-00574-Y"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00210-020-01976-1"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23123267"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170705114456"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/BIOMEDICINES9080887"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.INTIMP.2021.107805"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.FCT.2019.04.031"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12012-021-09646-1"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/KI.2012.226"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3140680"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03157-7"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001085"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/369784"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-04785-z"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.LFS.2021.120071"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.529075"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13075-022-02740-X"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.4103\/CJP.CJP_13_21"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2018.07.002"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-48382-5_15"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172422"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-8871-2_19"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.04.022"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11255-021-03093-1"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JSBMB.2020.105789"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/FCIMB.2013.00014\/BIBTEX"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLIMM.2016.05.001"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.1108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T21:08:29Z","timestamp":1692306509000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.1108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,9]]},"references-count":67,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/prp2.1108"],"URL":"https:\/\/doi.org\/10.1002\/prp2.1108","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,9]]},"assertion":[{"value":"2022-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01108"}}