Antioxidant vitamin therapy alters burn trauma-mediated cardiac NF-kappaB activation and cardiomyocyte cytokine secretion

J Trauma. 2001 Mar;50(3):397-406; discussion 407-8. doi: 10.1097/00005373-200103000-00002.

Abstract

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.

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-kappaB and interrupting cardiac inflammatory cytokine secretion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Body Surface Area
  • Burns / classification
  • Burns / complications*
  • Burns / immunology*
  • Burns / physiopathology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Hemodynamics / drug effects
  • Hemodynamics / immunology
  • Inflammation
  • Injury Severity Score
  • Interleukin-1 / metabolism*
  • Interleukin-6 / metabolism*
  • Myocardial Contraction / drug effects*
  • Myocardial Contraction / immunology*
  • Myocardium / cytology
  • Myocardium / immunology*
  • Myocardium / metabolism*
  • NF-kappa B / drug effects*
  • NF-kappa B / immunology*
  • Oxidative Stress / immunology*
  • Protein Transport / drug effects*
  • Protein Transport / immunology*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*
  • Vitamin A / pharmacology
  • Vitamin A / therapeutic use*
  • Vitamin E / pharmacology
  • Vitamin E / therapeutic use*

Substances

  • Antioxidants
  • Interleukin-1
  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vitamin A
  • Vitamin E
  • Ascorbic Acid