{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:25:54Z","timestamp":1788449154776,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009659","name":"Guangzhou Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Allopurinol (ALP) attenuates oxidative stress and diabetic cardiomyopathy (DCM), but the mechanism is unclear. Activation of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) following the disassociation with its repressor Keap1 under oxidative stress can maintain inner redox homeostasis and attenuate DCM with concomitant attenuation of autophagy. We postulated that ALP treatment may activate Nrf2 to mitigate autophagy over\u2010activation and consequently attenuate DCM. Streptozotocin\u2010induced type 1 diabetic rats were untreated or treated with ALP (100\u00a0mg\/kg\/d) for 4\u00a0weeks and terminated after heart function measurements by echocardiography and pressure\u2010volume conductance system. Cardiomyocyte H9C2 cells infected with Nrf2 siRNA or not were incubated with high glucose (HG, 25\u00a0mmol\/L) concomitantly with ALP treatment. Cell viability, lactate dehydrogenase, 15\u2010F2t\u2010Isoprostane and superoxide dismutase (SOD) were measured with colorimetric enzyme\u2010linked immunosorbent assays. ROS, apoptosis, was assessed by dihydroethidium staining and TUNEL, respectively. The Western blot and qRT\u2010PCR were used to assess protein and mRNA variations. Diabetic rats showed significant reductions in heart rate (HR), left ventricular eject fraction (LVEF), stroke work (SW) and cardiac output (CO), left ventricular end\u2010systolic volume (LVVs) as compared to non\u2010diabetic control and ALP improved or normalized HR, LVEF, SW, CO and LVVs in diabetic rats (all\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.05). Hearts of diabetic rats displayed excessive oxidative stress manifested as increased levels of 15\u2010F2t\u2010Isoprostane and superoxide anion production, increased apoptotic cell death and cardiomyocytes autophagy that were concomitant with reduced expressions of Nrf2, heme oxygenase\u20101 (HO\u20101) and Keap1. ALP reverted all the above\u2010mentioned diabetes\u2010induced biochemical changes except that it did not affect the levels of Keap1. In vitro, ALP increased Nrf2 and reduced the hyperglycaemia\u2010induced increases of H9C2 cardiomyocyte hypertrophy, oxidative stress, apoptosis and autophagy, and enhanced cellular viability. Nrf2 gene silence cancelled these protective effects of ALP in H9C2 cells. Activation of Nrf2 subsequent to the suppression of Keap1 and the mitigation of autophagy over\u2010activation may represent major mechanisms whereby ALP attenuates DCM.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.14870","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T12:38:50Z","timestamp":1576759130000},"page":"1760-1773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Allopurinol reduces oxidative stress and activates Nrf2\/p62 to attenuate diabetic cardiomyopathy in rats"],"prefix":"10.1111","volume":"24","author":[{"given":"Jierong","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital Guangzhou Medical University Guangzhou China"},{"name":"Department of Anesthesiology The University of Hong Kong Hong Kong 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