Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion.
BACKGROUND
Activated protein C (APC) is a serine protease with anticoagulant and ant-inflammatory activities. APC has been shown to attenuate deleterious effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to investigate the effects of APC on intestinal mucosal injury induced by superior mesenteric occlusion.


METHODS
Male Wistar-albino rats were allocated into four groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to Group 1 except for APC treatment (n = 12); (3) I/R group, 60 min of ischemia followed by 3-h of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 mug/kg injection of APC intravenously, 15 min before reperfusion (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale from 0 to 5, histopathologically, and by measuring activities of oxidative and antioxidative enzymes as well as nitrate/nitrite levels, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. Animal survival was observed up to 1 wk.


RESULTS
Intestinal mucosal injury scores were significantly decreased with APC administration (P < 0.05). APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the intestinal tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes in the intestinal tissues (P < 0.05). Intestinal edema was significantly alleviated with APC treatment (P < 0.05). The survival rate of rats in the APC-treated group were significantly higher than that of the I/R-treated group (P < 0.05).


CONCLUSIONS
This study clearly showed that APC treatment significantly attenuated intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether APC has a useful role in reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.
Department of General Surgery, Pamukkale University, School of Medicine, Denizli, Turkey. zteke_md@yahoo.com
Zafer
Z
Teke
Mustafa
M
Sacar
Cigdem
C
Yenisey
A Ozgur
AO
Atalay
Tulay
T
Kavak
Ergun
E
Erdem
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D004487:Edema / Q000517:prevention & control; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017538:Mesenteric Artery, Superior; D008641:Mesenteric Vascular Occlusion / Q000188:drug therapy*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D011486:Protein C / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D052096:Warm Ischemia; D014969:Xanthine Oxidase / Q000378:metabolism
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D009566:Nitrates; D009573:Nitrites; D011486:Protein C; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D; D008315:Malondialdehyde; D010544:Peroxidases; D014969:Xanthine Oxidase; D005980:Glutathione Reductase; D005978:Glutathione