Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury.
BACKGROUND
We have shown that both intraischemic hypothermia and hypertonic saline resuscitation provide dramatic protection against gut ischemia/reperfusion (I/R) injury that is in part mediated by heme oxygenase-1 (HO-1). We therefore hypothesized that induction of HO-1 by hemin would lessen damage and improve function after gut I/R.


METHODS
Male Sprague-Dawley rats were treated with 50 micromol/kg hemin (HO-1 inducer ferric protoporphyrin IX chloride) sq or vehicle 2 h before superior mesenteric artery occlusion for 60 min or sham laparotomy. After 6 h of reperfusion, transit was determined by quantitation of percentage of tracer in 10 equal segments of small intestine 30 min following injection into the duodenum (expressed as mean geometric center). Ileum was harvested for assessment of mucosal histologic injury (Chiu score 0-5 by blinded observer), myeloperoxidase activity (MPO, index of inflammation), and HO-1 protein expression.


RESULTS
Hemin treatment was associated with increased HO-1 protein expression, lessened mucosal injury, decreased MPO activity, and improved intestinal transit following gut I/R.


CONCLUSIONS
These data corroborate that HO-1 plays an important role in protecting the gut against I/R-induced injury.
Attuwaybi
B O
BO
Department of Surgery, University of Texas-Houston School of Medicine, Houston, Texas 77030, USA.
Kozar
R A
RA
Moore-Olufemi
S D
SD
Sato
N
N
Hassoun
H T
HT
Weisbrodt
N W
NW
Moore
F A
FA
D000818:Animals; D004790:Enzyme Induction; D005772:Gastrointestinal Transit / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007422:Intestines / Q000098:blood supply*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D006427:Hemin; D009195:Peroxidase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1