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Ethyl pyruvate prevents acute lung injury in an experimental multitrauma model

Introduction

Ethyl pyruvate (EP) is a pyruvate derivative that has been reported to improve survival, to decrease proinflammatory cytokine expression (including high mobility group box-1) and to ameliorate organ dysfunction in animals who have lethal sepsis or were subjected to hemorrhagic shock. We examined the potential protective effects of EP administered after multi-trauma on lung oxidative damage and apoptosis in a rat model with delayed resuscitation.

Materials and methods

Thirty-two male Wistar rats were equally divided into sham-control, multi-trauma, EP and multi-trauma + EP treatment groups. Anesthesia was performed with ketamine hydrochloride (60 mg/kg, intramuscularly) in all groups. Multi-trauma was applied as a moderate head trauma, left femur and tibia fractures under anesthesia. Head trauma was created using impaction model; a 450 g weight was dropped on to a metal plate fixed to the head of the subjects from a 1 m height through a Plexiglas guide tube [1]. The fractures of the tibia and femur were created by dropping a blunt guillotine with a weight of 500 g [2]. The first and third groups were resuscitated with Ringer lactate solution. EP (as a Ringer ethyl pyruvate solution; Sigma) was administered 40 mg/kg intraperitoneally 6 hours after the multi-trauma and animals were sacrificed at 24 hours. Post-trauma treatment with EP after the multi-trauma prevented the increase in lung tissue TBARS levels and serum MPO levels (Figs 1 and 2; P < 0.05). Lung tissue histopathology demonstrated a dramatic reduction in neutrophil infiltration and caspase-stained cells in the multi-trauma + EP group.

figure1

Figure 1

figure2

Figure 2

Discussion and conclusion

These results suggest that a single dose of EP inhibits leukocyte infiltration and oxidative lung damage, even when given 6 hours after the multi-trauma. EP warrants further evaluation as a therapeutic agent to ameliorate multi-traumainduced acute lung injury.

References

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Cinel, I., Oztuna, V., Karabacak, T. et al. Ethyl pyruvate prevents acute lung injury in an experimental multitrauma model. Crit Care 10, P179 (2006). https://doi.org/10.1186/cc4526

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Keywords

  • Acute Lung Injury
  • Ethyl Pyruvate
  • Proinflammatory Cytokine Expression
  • Ringer Lactate Solution
  • Lethal Sepsis