Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Wen JJ

PROVIDER: S-EPMC9634710 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Wen Jake J JJ Mobli Keyan K Rontoyanni Victoria G VG Cummins Claire B CB Radhakrishnan Geetha L GL Murton Andrew A Radhakrishnan Ravi S RS

Journal of the American College of Surgeons 20220401 4

<h4>Background</h4>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 pat ...[more]

PMID: 35290286

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Dataset Information

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

Background

Study design

Results

Conclusions

Publications

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

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