Antioxidant Vitamin Therapy Alters Burn Trauma-Mediated Cardiac NF-??B Activation and Cardiomyocyte Cytokine Secretion

Publisher Website
Google Scholar
Abstract
Background This study examined the effects of antioxidant vitamins A, C, and E on nuclear transcription factor-κ B (NF-κB) nuclear translocation, on secretion of inflammatory cytokines by cardiac myocytes, and on cardiac function after major burn trauma. Methods Adult rats were divided into four experimental groups: group I, shams; group II, shams given oral antioxidant vitamins (vitamin C, 38 mg/kg; vitamin E, 27 U/kg; vitamin A, 41 U/kg 24 hours before and immediately after burn); group III, burns (third-degree scald burn over 40% total body surface area) given lactated Ringer’s solution (4 mL/kg/% burn); and group IV, burns given lactated Ringer’s solution plus vitamins as described above. Hearts were collected 4, 8, 12, and 24 hours after burn to assay for NF-κB nuclear translocation, and hearts collected 24 hours after burn were examined for cardiac contractile function or tumor necrosis factor-α secretion by cardiomyocytes. Results Compared with shams, left ventricular pressure was lower in burns given lactated Ringer’s solution (group III) (88 ± 3 vs. 64 ± 5 mm Hg, p < 0.01) as was +dP/dt max (2,190 ± 30 vs. 1,321 ± 122 mm Hg/s) and −dP/dt max (1,775 ± 71 vs. 999 ± 96 mm Hg, p < 0.01). Burn injury in the absence of vitamin therapy (group III) produced cardiac NF-κB nuclear migration 4 hours after burn and cardiomyocyte secretion of tumor necrosis factor-α, interleukin-1β, and interleukin-6 by 24 hours after burn. Antioxidant therapy in burns (group IV) improved cardiac function, producing left ventricular pressure and ±dP/dt (82 ± 2 mm Hg, 1,880 ± 44 mm Hg, and 1,570 ± 46 mm Hg/s) comparable to those measured in shams. Antioxidant vitamins in burns inhibited NF-κB nuclear migration at all times after burn and reduced burn-mediated cytokine secretion by cardiomyocytes. Conclusion These data suggest that antioxidant vitamin therapy in burn trauma provides cardioprotection, at least in part, by inhibiting translocation of the transcription factor NF-κB and interrupting cardiac inflammatory cytokine secretion.