Nuclear Factor Erythroid 2-Related Factor 2 Activation and Burn-Induced Cardiac Dysfunction.

Autor:	Wen JJ; From the Departments of Surgery (Wen, Mobli, Rontoyanni, Cummins, Murton, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX., Mobli K; From the Departments of Surgery (Wen, Mobli, Rontoyanni, Cummins, Murton, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX., Rontoyanni VG; From the Departments of Surgery (Wen, Mobli, Rontoyanni, Cummins, Murton, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX., Cummins CB; From the Departments of Surgery (Wen, Mobli, Rontoyanni, Cummins, Murton, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX., Radhakrishnan GL; Pediatrics (GL Radhakrishnan, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX., Murton A; From the Departments of Surgery (Wen, Mobli, Rontoyanni, Cummins, Murton, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX., Radhakrishnan RS; From the Departments of Surgery (Wen, Mobli, Rontoyanni, Cummins, Murton, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX.; Pediatrics (GL Radhakrishnan, RS Radhakrishnan), University of Texas Medical Branch at Galveston, Galveston, TX.
Jazyk:	angličtina
Zdroj:	Journal of the American College of Surgeons [J Am Coll Surg] 2022 Apr 01; Vol. 234 (4), pp. 660-671.
DOI:	10.1097/XCS.0000000000000119
Abstrakt:	Background: Our previous studies have found that burn injury induces cardiac dysfunction through interruption of the antioxidant-response element (ARE) pathway in cardiac mitochondria. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator that activates many antioxidant enzymes. Oltipraz (Olti) is a Nrf2 activator and a well-known inducer of NQO1 along with other enzymes that comprise the Nrf2-associated antioxidants. We propose that Nrf2 activation will induce the ARE pathway, leading to abrogation of burn-induced cardiac dysfunction. Study Design: In this study, we investigated the effect of Nrf2-deficiency in mice on burn-induced cardiac dysfunction. Wild-type (WT) and Nrf2-deficient mice received 30% total body surface area burn injury and were treated with or without Olti and then harvested at 3 hours and 24 hours post burn (3 hpb and 24 hpb). Results: As expected, Nrf2-deficient mice exhibited exacerbated cardiac dysfunction after burn injury, as measured by Vevo 2100 echocardiography. Electron microscopy showed that Nrf2 depletion worsened burn injury-induced cardiac mitochondrial damage. In addition, Nrf2 depletion increased cardiac mitochondrial dysfunction and myocardial fibrosis after burn injury. Treatment with Olti ameliorated the heart dysfunction in burned Nrf2-/+ mice, improved cardiac mitochondrial structure and oxidative phosphorylation, as well as decreased cardiac fibrosis. These results suggest that Nrf2 and its downstream targets modulate cardiac function after burn injury. Conclusions: In summary, Nrf2 depletion worsens cardiac dysfunction after burn injury. Nrf2 activation, with a drug such as Olti, offers a promising therapeutic strategy for abrogating burn-induced cardiac dysfunction. (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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