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Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion.
J Surg Res. 2008 Oct; 149(2):219-30.JS

Abstract

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.

MATERIALS AND 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.

Authors+Show Affiliations

Department of General Surgery, Pamukkale University, School of Medicine, Denizli, Turkey. zteke_md@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18533185

Citation

Teke, Zafer, et al. "Activated Protein C Attenuates Intestinal Mucosal Injury After Mesenteric Ischemia/reperfusion." The Journal of Surgical Research, vol. 149, no. 2, 2008, pp. 219-30.
Teke Z, Sacar M, Yenisey C, et al. Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion. J Surg Res. 2008;149(2):219-30.
Teke, Z., Sacar, M., Yenisey, C., Atalay, A. O., Kavak, T., & Erdem, E. (2008). Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion. The Journal of Surgical Research, 149(2), 219-30. https://doi.org/10.1016/j.jss.2007.10.011
Teke Z, et al. Activated Protein C Attenuates Intestinal Mucosal Injury After Mesenteric Ischemia/reperfusion. J Surg Res. 2008;149(2):219-30. PubMed PMID: 18533185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion. AU - Teke,Zafer, AU - Sacar,Mustafa, AU - Yenisey,Cigdem, AU - Atalay,A Ozgur, AU - Kavak,Tulay, AU - Erdem,Ergun, Y1 - 2007/11/21/ PY - 2007/07/14/received PY - 2007/08/21/revised PY - 2007/10/12/accepted PY - 2008/6/6/pubmed PY - 2008/10/15/medline PY - 2008/6/6/entrez SP - 219 EP - 30 JF - The Journal of surgical research JO - J Surg Res VL - 149 IS - 2 N2 - 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. MATERIALS AND 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. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/18533185/Activated_protein_C_attenuates_intestinal_mucosal_injury_after_mesenteric_ischemia/reperfusion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(07)00616-6 DB - PRIME DP - Unbound Medicine ER -