Volume 2 Supplement 1

ESICM LIVES 2014

Open Access

1069. Pharmacological preconditioning with vitamin c attenuates intestinal injury via the induction of heme oxygenase-1 after hemorrhagic shock in rats

  • B Zhao1,
  • J Fei1,
  • Y Chen1,
  • X-Q Song1,
  • L Ma1,
  • L Wang1,
  • E-Z Chen1 and
  • E-Q Mao1
Intensive Care Medicine Experimental20142(Suppl 1):P85

DOI: 10.1186/2197-425X-2-S1-P85

Published: 26 September 2014

Introduction

Pre-induction of heme oxygenase (HO)-1, which is regarded as an effective method of “organ preconditioning”, exerts beneficial effects during hemorrhagic shock (HS). However, the available HO-1 inducers exhibit disadvantages such as toxicity or complex technical requirements. Therefore, a safe and convenient HO-1 inducer would be promising and could be exploited in the treatment of foreseeable hemorrhaging, such as prior to major surgery. Recently, vitamin C (VitC) has been shown to attenuate organ injuries and inhibit inflammatory responses in hemorrhagic shock [3], but the specific mechanism remains unclear. Studies on the relationship between HO-1 and VitC are limited, and the results are controversial[4, 5].

Objectives

We investigated the effect of vitamin C (VitC) on intestinal HO-1 expression and the involved mechanism. We further investigated if VitC pretreatment prevented HS related intestinal tissue injuries via HO-1 induction.

Methods

The IEC-6 were treated with grade concentration of VitC as well as SB203580, PD98059 and SP600125, the inhibitors of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK). SD rats were pretreated with VitC (intraperitoneally, 100mg/Kg), HS was induced by drawing blood from the rat femoral artery (mean arterial pressure = 30 mm Hg) for 1 hr and resuscitating with the shed blood and Ringer's solution. Some rats further received zinc protoporphyrin (Znpp, intraperitoneally, 3 mg/kg), a HO-1 inhibitor.

Results

The in vitro study showed HO-1 was induced in IEC-6 cell in a time- and concentration- dependent manner by VitC, and the inhibitor of ERK1/2 PD98059 inhibited the VitC induced HO-1 expression. The in vivo study showed the HO-1 protein (mainly observed in intestinal epithelial cells) and activity in intestine were highly induced in normal rat, and these HO-1 levels were further enhanced in HS rat model. The histological damage, apoptosis (number of TUNEL positive cell, Bcl-2/Bax ratio), neutophil infiltration (number of MPO positive cells, MPO activity and MPO protein level), and inflammatory cytokines level of tumor necrosis factor-a and interleukin-6 were all relieved by VitC pretreatment, and the protective effect of VitC was attenuated by Znpp.
Figure 1

The schematic diagram of the main in vivo protocol

Conclusions

These data suggests VitC might be applied as a safe inducer of intestinal HO-1 and VitC pretreatment attenuated HS related intestinal injuries via induction of HO-1 by activating ERK1/2 pathway.

Declarations

Grant acknowledgment

This work is supported by National Natural Science Foundation of China projects 81171789

Authors’ Affiliations

(1)
Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine

References

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Copyright

© Zhao et al; licensee Springer. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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