Effects of methylprednisolone on inflammatory activity and oxidative stress in the lungs of brain-dead rats

J Bras Pneumol. 2013 Mar-Apr;39(2):173-80. doi: 10.1590/S1806-37132013000200008.
[Article in English, Portuguese]

Abstract

Objective: To evaluate the effects that early and late systemic administration of methylprednisolone have on lungs in a rat model of brain death.

Methods: Twenty-four male Wistar rats were anesthetized and randomly divided into four groups (n = 6 per group): sham-operated (sham); brain death only (BD); brain death plus methylprednisolone (30 mg/kg i.v.) after 5 min (MP5); and brain death plus methylprednisolone (30 mg/kg i.v.) after 60 min (MP60). In the BD, MP5, and MP60 group rats, we induced brain death by inflating a balloon catheter in the extradural space. All of the animals were observed and ventilated for 120 min. We determined hemodynamic and arterial blood gas variables; wet/dry weight ratio; histological score; levels of thiobarbituric acid reactive substances (TBARS); superoxide dismutase (SOD) activity; and catalase activity. In BAL fluid, we determined differential white cell counts, total protein, and lactate dehydrogenase levels. Myeloperoxidase activity, lipid peroxidation, and TNF-α levels were assessed in lung tissue.

Results: No significant differences were found among the groups in terms of hemodynamics, arterial blood gases, wet/dry weight ratio, BAL fluid analysis, or histological score-nor in terms of SOD, myeloperoxidase, and catalase activity. The levels of TBARS were significantly higher in the MP5 and MP60 groups than in the sham and BD groups (p < 0.001). The levels of TNF-α were significantly lower in the MP5 and MP60 groups than in the BD group (p < 0.001).

Conclusions: In this model of brain death, the early and late administration of methylprednisolone had similar effects on inflammatory activity and lipid peroxidation in lung tissue.

OBJETIVO:: Avaliar os efeitos da administração sistêmica precoce e tardia de metilprednisolona nos pulmões em um modelo de morte encefálica em ratos.

MÉTODOS:: Vinte e quatro ratos Wistar machos foram anestesiados e randomizados em quatro grupos (n = 6 por grupo): sham, somente morte encefálica (ME), metilprednisolona i.v. (30 mg/kg) administrada 5 min após a morte encefálica (MP5) e 60 min após a morte encefálica (MP60). Os grupos ME, MP5 e MP60 foram submetidos à morte encefálica por insuflação de um balão no espaço extradural. Todos os animais foram observados e ventilados durante 120 min. Foram determinadas variáveis hemodinâmicas e gasométricas, relação peso úmido/seco, escore histológico, thiobarbituric acid reactive substances (TBARS, substâncias reativas ao ácido tiobarbitúrico), atividade de superóxido dismutase (SOD) e de catalase, assim como contagem diferencial de células brancas, proteína total e nível de desidrogenase lática no LBA. A atividade da mieloperoxidase, peroxidação lipídica e níveis de TNF-α foram avaliados no tecido pulmonar.

RESULTADOS:: Não foram observadas diferenças significativas nas variáveis hemodinâmicas e gasométricas, relação peso úmido/seco, análises do LBA, escore histológico, SOD, mieloperoxidase e catalase entre os grupos. Os níveis de TBARS foram significativamente maiores nos grupos MP5 e MP60 do que nos grupos sham e ME (p < 0,001). Os níveis de TNF-α foram significativamente menores nos grupos MP5 e MP60 do que no grupo ME (p < 0,001).

CONCLUSÕES:: Neste modelo de morte cerebral, a administração precoce e tardia de metilprednisolona apresentou efeitos semelhantes sobre a inflamação e a peroxidação lipídica no tecido pulmonar.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain Death*
  • Disease Models, Animal
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Inflammation / metabolism
  • Lung / metabolism*
  • Lung Injury / prevention & control
  • Male
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / pharmacology*
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Thiobarbituric Acid Reactive Substances / metabolism*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Glucocorticoids
  • Thiobarbituric Acid Reactive Substances
  • Tumor Necrosis Factor-alpha
  • Methylprednisolone