Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine.
OBJECTIVE
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.


CONCLUSIONS
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.
Mallick
Ismail H
IH
University Department of Surgery, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom.
Yang
Wen-Xuan
WX
Winslet
Marc C
MC
Seifalian
Alexander M
AM
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D007421:Intestine, Small / Q000098:blood supply / Q000201:enzymology / Q000293:injuries*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D013859:Thiocarbamates / Q000494:pharmacology*
D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat