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Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2005; 11(46): 7308-7313
Published online Dec 14, 2005. doi: 10.3748/wjg.v11.i46.7308
Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine
Ismail H Mallick, Wen-Xuan Yang, Marc C Winslet, Alexander M Seifalian
Ismail H Mallick, Wen-Xuan Yang, Marc C Winslet, Alexander M Seifalian, GI and Hepatobiliary Research Unit, University Department of Surgery, Royal Free and University College Medical School, University College London, London, United Kingdom
Ismail H Mallick, Marc C Winslet, Department of Surgery, Royal Free Hospital Hampstead NHS Trust, London, United Kingdom
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Alexander M Seifalian, University Department of Surgery, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom. a.seifalian@medsch.ucl.ac.uk
Telephone: +44-20-78302901 Fax: +44-20-74726444
Received: February 13, 2005
Revised: April 23, 2005
Accepted: April 26, 2005
Published online: December 14, 2005
Abstract

AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR injury.

METHODS: Eighteen male rats were randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC treatment before IR. Intestinal microvascular perfusion (IMP) was monitored continuously by laser Doppler flowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion period.

RESULTS: At the end of the reperfusion in the IR group, IMP recovered partially to 42.5% of baseline (P<0.05 vs sham), whereas PDTC improved IMP to 67.3% of baseline (P<0.01 vs IR). There was a twofold increase in HO activity in PDTC group (2 062.66±106.11) as compared to IR (842.3±85.12) (P<0.001). LDH was significantly reduced (P<0.001) in PDTC group (585.6±102.4) as compared to IR group (1 973.8±306.5). Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR group.

CONCLUSION: Our study demonstrates that PDTC improves the IMP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine.

Keywords: Intestine, Ischemia-reperfusion injury, Heme oxygenase, Pyrrolidine