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Swiss albino mice exposed to CdCl<jats:sub>2<\/jats:sub> intraperitoneally (I.P.) (1\u2009mg\/kg b.w.; 12 weeks) showed increased release of lactate dehydrogenase in bronchoalveolar lavage fluid, generating reactive oxygen species, impaired antioxidant enzymes function, and disrupted alveolar structure along with increased expression of Angiotensin\u2010II (Ang\u2010II) in lung tissue. Cd\u2010induced angiotensin\u2010converting enzyme\u20102\u2010Ang\u2010II axis imbalance triggered the onset of Ang\u2010II induced tumour necrosis factor alpha\u00a0 (TNF\u2010\u03b1) mediated necroptosis by upregulating the signalling molecules RIP\u20101, RIP\u20103, and p\u2010mixed lineage kinase domain\u2010like. In an in vitro study, colocalization of Ang\u2010II\u2010RIP\u20103 molecule in Cd intoxicated L\u2010132 cells (human alveolar epithelial cell line), as well as pretreatment of Cd exposed cells with the inhibitor's captopril (10\u2009\u03bcM), necrostatin\u20101 (50\u2009\u03bcM), and etanercept (5\u2009\u03bcg\/ml) indicated TNF\u2010\u03b1 induced necroptotic cell death via activation of the key molecule, Ang\u2010II. Moreover, Ang\u2010II disrupted the alveolar\u2010capillary barrier by decreasing tight junctional proteins (zonula occludens\u20101 and occludin) and endothelial VE\u2010cadherin expression. The use of human umbilical vein endothelial cells as a model of junctional protein\u2010expressing cells showed that captopril pretreatment (25\u2009\u03bcM) restored VE\u2010cadherin expression in Cd\u2010treated human umbilical vein endothelial cells. In CdCl<jats:sub>2<\/jats:sub> intoxicated mice, melatonin pretreatment (10\u2009mg\/kg b.w.; 12 weeks, I.P.) inhibited inflammatory mediators (TNF\u2010\u03b1, interleukin [IL]\u20101\u03b2, and IL\u20106) release and effectively suppressed (Cd\u2010induced) Ang\u2010II mediated necroptotic cell death and alveolar\u2010capillary breaching due to Cd toxicity.<\/jats:p>","DOI":"10.1002\/jbt.23163","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T06:56:48Z","timestamp":1658127408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Melatonin counteracts necroptosis and pulmonary edema in cadmium\u2010induced chronic lung injury through the inhibition of angiotensin II"],"prefix":"10.1002","volume":"36","author":[{"given":"Sushweta","family":"Mahalanobish","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine Bose Institute Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukanya","family":"Saha","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine Bose Institute Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayanta","family":"Dutta","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine Bose Institute Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumit","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine Bose Institute Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0190-5904","authenticated-orcid":false,"given":"Parames C.","family":"Sil","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine Bose Institute Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Toxicological Profile for Cadmium","author":"Faroon O.","year":"2012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph110101049"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1mt00066g"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.07.043"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-015-0598-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24224176"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20082027"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1179\/oeh.2007.13.2.202"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/milmed\/145.6.435"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2014.04.008"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039809"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304-0733OC"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.4.1907-1916.2005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resinv.2016.03.008"},{"key":"e_1_2_7_16_1","volume":"7","author":"Sun H.","year":"2019","journal-title":"Injury"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.036"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.031"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.184"},{"issue":"286","key":"e_1_2_7_20_1","volume":"169","author":"Gong Y.\u2010N.","year":"2017","journal-title":"Cell"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx490"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/675984"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03871"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00029.2016"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317015"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S265718"},{"key":"e_1_2_7_27_1","first-page":"3","volume":"23","author":"Reiter R. 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