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Ethyl pyruvate prevents acute lung injury in an experimental multitrauma model
Critical Care volume 10, Article number: P179 (2006)
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.
![figure 1](http://media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fcc4526/MediaObjects/13054_2006_Article_4057_Fig1_HTML.jpg)
Figure 1
![figure 2](http://media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fcc4526/MediaObjects/13054_2006_Article_4057_Fig2_HTML.jpg)
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
Foda MA, Marmarou A: A new model of diffuse brain injury in rats. Part II: morphological characterization. J Neurosurg 1994, 80: 301-313. 10.3171/jns.1994.80.2.0301
Bonnarens F, Einhorn TA: Production of a standard closed fracture in laboratory animal bone. J Orthop Res 1984, 2: 97-101. 10.1002/jor.1100020115
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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 (Suppl 1), P179 (2006). https://doi.org/10.1186/cc4526
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DOI: https://doi.org/10.1186/cc4526