{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:04:04Z","timestamp":1773803044907,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"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":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Azilsartan is found to be more potent than other angiotensin receptor blockers\u00a0in reducing blood pressure. However, its effect on the heart following myocardial infarction remains to be established. For the first time, we investigated the peroxisome proliferator\u2010activated receptor\u2010\u03b3\u00a0(PPAR\u2010\u03b3) agonistic and cardioprotective properties of azilsartan. Computational modeling studies of interactions between azilsartan and PPAR\u2010\u03b3 revealed azilsartan as an agonist of PPAR\u2010\u03b3 and showed the mechanism of azilsartan in cardioprotection. Our study compared the cardioprotective potential of telmisartan to that of azilsartan in a murine model of myocardial ischemia\u2010reperfusion injury\u00a0by comparing their antioxidant, ant apoptotic, anti\u2010inflammatory, mitogen\u2010activated protein kinase (MAPK)\u2010modulating ability, and PPAR\u2010\u03b3 agonistic activity. Male Wistar rats were grouped into four to receive vehicle (dimethyl sulfoxide [0.05%] 2\u2009ml\/kg) telmisartan (10\u2009mg\/kg p.o.), azilsartan (10\u2009mg\/kg p.o.) or azilsartan with specific PPAR\u2010\u03b3 blocker, GW 9662 for 28 days. Ischemia was induced for 45\u2009min on the 29th day followed by 60\u2009min of reperfusion. Telmisartan and azilsartan pretreatment significantly nearly normalized cardiac parameters and preserved structural changes. Both drugs inhibited oxidative burst, inflammation, as well as cell death by modulating apoptotic protein expression along with reduction in 4\u2032,6\u2010diamidino\u20102\u2010phenylindole\/terminal deoxynucleotidyl transferase dUTP nick end labeling\u2010positive cells. An increment in pro\u2010survival kinase ERK paralleled with a reduction in p38 and JNK was also revealed by MAPK pathway studies, after administration of these drugs. Interestingly, the aforementioned changes induced by both drugs were reversed by administration of the specific PPAR\u2010\u03b3 antagonist, GW9662. However, we found that azilsartan upregulated PPAR\u2010\u03b3 to a lesser extent as compared to telmisartan and the latter may be preferred in hypertensive patients at risk of myocardial infarction.<\/jats:p>","DOI":"10.1002\/jbt.22785","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T22:37:26Z","timestamp":1618612646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cardioprotective effects of azilsartan compared with that of telmisartan on an in vivo model of myocardial ischemia\u2010reperfusion injury"],"prefix":"10.1002","volume":"35","author":[{"given":"Shanky","family":"Garg","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Cardiovascular Research Laboratory All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sana Irfan","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiovascular Research Laboratory All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajiv Kumar","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiovascular Research Laboratory All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manish Kumar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Anatomy All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biosphysics All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Punit","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Biosphysics All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tapas Chandra","family":"Nag","sequence":"additional","affiliation":[{"name":"Department of Anatomy All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruma","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pathology All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1919-4701","authenticated-orcid":false,"given":"Jagriti","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiovascular Research Laboratory All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dharamvir Singh","family":"Arya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.domaniend.2020.106440"},{"key":"e_1_2_7_3_1","first-page":"124","volume":"10","author":"Khosravi F.","year":"2018","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0355-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11857"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000496164"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117108"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01377.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2012.147"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-13-30"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2019.104604"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-019-06900-1"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214727"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.08.041"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8095825"},{"key":"e_1_2_7_16_1","first-page":"1","volume":"2016","year":"2016","journal-title":"Oxid. Med. Cell. Longev"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(79)90289-7"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03714.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.09.187"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B"},{"key":"e_1_2_7_23_1","first-page":"43","article-title":"Dynamics Simulations on Commodity Clusters","volume":"2006","year":"2006","journal-title":"In Proc. 2006 ACM\/IEEE Conf. Supercomp"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-016-6650-9"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109407"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103611"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8095825"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-019-00011-2"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111251"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.211722"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2012.17"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.07.012"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22785","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.22785","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22785","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T12:26:06Z","timestamp":1692966366000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.22785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,16]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/jbt.22785"],"URL":"https:\/\/doi.org\/10.1002\/jbt.22785","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,16]]},"assertion":[{"value":"2020-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22785"}}