Antioxidant vitamin therapy alters burn trauma-mediated cardiac NF-kappaB activation and cardiomyocyte cytokine secretion.
BACKGROUND
This study examined the effects of antioxidant vitamins A, C, and E on nuclear transcription factor-kappa B (NF-kappaB) 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-kappaB nuclear translocation, and hearts collected 24 hours after burn were examined for cardiac contractile function or tumor necrosis factor-alpha 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-kappaB nuclear migration 4 hours after burn and cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin-1beta, 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-kappaB nuclear migration at all times after burn and reduced burn-mediated cytokine secretion by cardiomyocytes.


CONCLUSIONS
These data suggest that antioxidant vitamin therapy in burn trauma provides cardioprotection, at least in part, by inhibiting translocation of the transcription factor NF-kappaB and interrupting cardiac inflammatory cytokine secretion.
Horton
J W
JW
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA. jureta.horton@utsouthwestern.edu
White
D J
DJ
Maass
D L
DL
Hybki
D P
DP
Haudek
S
S
Giroir
B
B
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D001830:Body Surface Area; D002056:Burns / Q000145:classification / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects / Q000276:immunology; D007249:Inflammation; D015601:Injury Severity Score; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000276:immunology*; D009206:Myocardium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects* / Q000276:immunology*; D018384:Oxidative Stress / Q000276:immunology*; D021381:Protein Transport / Q000187:drug effects* / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014801:Vitamin A / Q000494:pharmacology / Q000627:therapeutic use*; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014801:Vitamin A; D014810:Vitamin E; D001205:Ascorbic Acid