Abstract
Nuclear factor (erythroid-derived 2)–like 2 (NRF2) is a basic leucine zipper transcription factor that principally defends against oxidative stress and also plays a unique role in severe sepsis. However, its contribution to intestinal injury and death after burn trauma is unclear.In this study, wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2−/−) mice were subjected to 15% or 30% total body surface area burn or sham injury. Survival, systemic inflammation, and gut injury were determined. Nrf2−/− mice were more susceptible to burn-induced intestinal injury, as characterized by increases in damage to the gut structure and in intestinal permeability. This exacerbation was associated with an increase in the intestinal mRNA expression of inflammatory cytokines (interleukin [IL]–6, IL-1B, monocyte chemotactic protein 1, intercellular adhesion molecule, and vascular cell adhesion molecule) and a decrease in the intestinal mRNA expression of Nrf2-regulated genes (NAD(P)H dehydrogenasequinine-1 and glutamate-cysteine ligase modifier subunit). Nrf2-deficient mice also showed a lower survival rate and higher levels of systemic cytokines (IL-6 and IL-1B) and high-mobility group protein B1 than wild-type mice. This study demonstrates for the first time that mice that lack Nrf2 are more susceptible to burn-induced intestinal injury and have more systemic inflammation and a lower survival rate.
Highlights
As a common surgical injury, burn trauma often induces a systemic inflammatory response syndrome that can progress to distant organ injury and multiple organ failure [1]
To determine the role of nuclear factor (erythroidderived 2)-like 2 (Nrf2) in burn injury, Nrf2+/+ and Nrf2−/− mice were subjected to 15% or 30% total body surface area (TBSA) burn injury, and their survival was monitored for 10 days
After 15% TBSA burn injury, more than 50% of Nrf2−/− mice died by the tenth day, but no deaths occurred in the Nrf2+/+ mice (Figure 1A)
Summary
As a common surgical injury, burn trauma often induces a systemic inflammatory response syndrome that can progress to distant organ injury and multiple organ failure [1]. To minimize this damage, efforts have been made to decrease the inflammatory response after burn injury [2]. The effects of oxidative stress in burn injuries have been well documented and are hypothesized to contribute to the development of distant organ injury or failure [5]. The short-term inflammation and long-term organ injury caused by burn injury have a close connection to oxidative stress and antioxidative reactions
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