Pyrrolidine dithiocarbamate protects the small bowel from warm ischaemia/reperfusion injury of the intestine: the role of haem oxygenase.
IR (ischaemia/reperfusion) injury of the intestine occurs commonly during abdominal surgery. We have previously shown that PDTC (pyrrolidine dithiocarbamate), an HO-1 (haem oxygenase-1) donor, improves intestinal microvascular perfusion. In the present study, we have investigated the effects of PDTC on the intestinal microcirculation following IR (ischaemia/reperfusion) injury of the intestine. Male Sprague-Dawley rats (n=72) were randomly assigned to four groups (n=18/group): (i) sham-operated group, who underwent laparotomy without induction of IR of the intestine; (ii) IR group, who were subjected to 30 min of superior mesenteric artery occlusion and 2 h of reperfusion; (iii) PDTC+IR group, who received PDTC prior to IR; and (iv) ZnPP group, who received the HO-1 inhibitor ZnPP (zinc protoporphyrin) followed by procedures as in group (iii). The ileum was evaluated for changes in tissue cytochrome c oxidase redox status, RBC (red blood cell) dynamics and leucocyte-endothelial interactions. The expression of HO-1 in the ileal tissue was examined at the end of the reperfusion. PDTC significantly improved the intestinal tissue oxygenation, mucosal perfusion index and RBC velocity compared with the IR and ZnPP groups. PDTC also decreased the leucocyte-endothelial interactions (P<0.05 compared with the IR and ZnPP groups). PDTC induced the expression of HO-1, whereas ZnPP abolished this effect.
Mallick
Ismail H
IH
Gastrointestinal and Hepatobiliary Research Unit, Academic Division of Surgical and Interventional Sciences, University College London, London, UK.
Winslet
Marc C
MC
Seifalian
Alexander M
AM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000502:physiology; D015153:Blotting, Western; D003250:Constriction; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D007082:Ileum / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D010084:Oxidation-Reduction; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D013859:Thiocarbamates / Q000494:pharmacology*
D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D006419:Heme Oxygenase (Decyclizing)