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. 2005 Dec 14;11(46):7308-13.
doi: 10.3748/wjg.v11.i46.7308.

Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine

Ismail H Mallick  1 , Wen-Xuan Yang, Marc C Winslet, Alexander M Seifalian
Affiliations

Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine

Ismail H Mallick et al. World J Gastroenterol. .

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.

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Figures

Figure 1
Figure 1
Intestinal microvascular perfusion in (% of baseline) during 30 min of ischemia and 2 h of reperfusion measured by L-DF. Values are expressed as mean±SE of six animals in each group (aP<0.05 vs IR). B: Baseline.
Figure 2
Figure 2
Ileal HO activity in all three experimental groups at the end of 2 h of reperfusion (bP<0.01 vs IR).
Figure 3
Figure 3
Serum LDH levels (U/L) at the end of 2 h reperfusion period. Values are expressed as mean±SE of six animals in each group. In PDTC group, LDH was significantly lower compared to the IR group (bP<0.001 vs IR).
Figure 4
Figure 4
Comparison of histological scores of ileal mucosa between three experimental groups (bP<0.01 vs IR).
Figure 5
Figure 5
Representative photomicrographs of histological sections of ileum (a) in sham operated animals, (b) subjected to 30-min period of ischemia and 2-h period of reperfusion (IR) and (c) subjected to PDTC+IR (H&E, original magnification ×100).
See this image and copyright information in PMC

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