Cerium Nitrate Treatment Provides Eschar Stabilization through Reduction in Bioburden, DAMPs, and Inflammatory Cytokines in a Rat Scald Burn Model

Abstract

Abstract In this study, we used a clinically relevant rat scald burn model to determine the treatment effects of cerium nitrate (CN) for stabilizing burn eschars through reduction of damage-associated molecular patterns (DAMPs), inflammatory cytokines, and bioburden. Forty-two male Sprague–Dawley rats were anesthetized before undergoing a scald burn at 99°C for 6 seconds to create a 10% full-thickness burn. The test groups included sham burn, burn with water bathing, and burn with CN bathing. End point parameters included circulating DAMPs, proinflammatory cytokines, tissue myeloperoxidase activity, and quantification of resident flora in burn skin. The high mobility group protein box 1 was found to be elevated in burn animals at postoperative days (POD) 1 and 7. CN significantly alleviated the increase (P < .05 at POD 1 and P < .01 at POD 7). CN also lessened the heightened levels of hyaluronan in burn animals (P < .05 at POD 7). Additionally, CN significantly reduced the burn-induced increases in interleukin-1β, growth-regulated oncogene/keratinocyte chemoattractant, and macrophage inflammatory protein-1α in burn wounds. The anti-inflammatory effect of CN was also demonstrated in its ability to mitigate the upregulated circulatory xanthine oxidase/dehydrogenase and increased tissue neutrophil infiltration in burn animals. Last, CN suppressed postburn proliferation of resident skin microbes, resulting in a significant 2-log reduction by POD 7. In conclusion, these results suggest that CN attenuates the burn-induced DAMPs, tissue inflammatory responses, and regrowth of resident skin flora, all of which collectively could improve the quality of burn eschar when applied at the point of injury in prolonged field care situations.