title: Pharmacological preconditioning with vitamin C attenuates intestinal injury via the induction of heme oxygenase-1 after hemorrhagic shock in rats.
abstract: 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. Here we investigated the effect of vitamin C (VitC), a common antioxidant, on intestinal HO-1 expression and examined whether VitC pretreatment prevented HS related intestinal tissue injuries after HO-1 induction. First, we conducted an in vitro study and found that HO-1 expression in rat intestinal epithelial cells (IEC-6) was induced by non-toxic VitC in a time and concentration dependent manner, and the mechanism was related to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Next, we conducted an in vivo study and found that VitC induced intestinal HO-1 protein expression (mainly observed in the intestinal epithelial cells) and HO-1 activity in normal SD rats, and that these HO-1 levels were further enhanced by VitC in a rat model of HS. The HS related intestinal injuries, including histological damage, pro-inflammatory cytokine levels (tumor necrosis factor and interleukin-6), neutrophil infiltration and apoptosis decreased after VitC pretreatment, and this alleviating of organ injuries was abrogated after the inhibition of HO-1 activity by zinc protoporphyrin-IX. It was of note that VitC did little histological damage to the intestine of the sham rats. These data suggested that VitC might be applied as a safe inducer of intestinal HO-1 and that VitC pretreatment attenuated HS related intestinal injuries via the induction of HO-1.
authors.affiliation: Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.affiliation: Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Ying
authors.affiliation: Department of Emergency Intensive Care Unit, the Third People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Song
authors.affiliation: Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Er-Zhen
authors.initials: EZ
authors.lastname: Chen
authors.affiliation: Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: En-Qiang
authors.initials: EQ
authors.lastname: Mao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007410:Intestinal Diseases / Q000201:enzymology / Q000517:prevention & control*; D007422:Intestines / Q000187:drug effects / Q000201:enzymology / Q000293:injuries*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000201:enzymology / Q000473:pathology
chemical_list: D000975:Antioxidants; D051547:Heme Oxygenase-1; D001205:Ascorbic Acid