Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 46; pp. 7308 - 7313
• Main Authors: Mallick, Ismail H, Yang, Wen-Xuan, Winslet, Marc C, Seifalian, Alexander M
• Format: Journal Article
• Language: English
• Published: United States Department of Surgery, Royal Free Hospital Hampstead NHS Trust, London, United Kingdom%GI and Hepatobiliary Research Unit, University Department of Surgery, Royal Free and University College Medical School, University College London, London,United Kingdom 14.12.2005; GI and Hepatobiliary Research Unit, University Department of Surgery, Royal Free and University College Medical School, University College London, London,United Kingdom; Baishideng Publishing Group Inc
• Subjects: Animals; Enzyme Induction - drug effects; Heme Oxygenase (Decyclizing) - biosynthesis; Intestine, Small - blood supply; Intestine, Small - enzymology; Intestine, Small - injuries; Male; Microcirculation - drug effects; Pyrrolidines - pharmacology; Rapid Communication; Rats; Rats, Sprague-Dawley; Reperfusion Injury - enzymology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Thiocarbamates - pharmacology; Ischemia-reperfusion injury; Pyrrolidine; Intestine; Heme oxygenase
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v11.i46.7308

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