Antithrombin-III Reduces Intestinal Ischemia/Reperfusion Deleterious Effects on Kidney: A Study in Rats

Abstract

Background: Mesenteric ischemia-reperfusion (I/R) is a well-known cause for both local and remote organ injuries. A natural inhibitor of serine proteases, Antithrombin-III, was previously shown to attenuate the tissue damage after local I/R in several organ systems. Here, we examined the effects of Antithrombin-III on renal injury, after mesenteric I/R. Methods: Female Wistar Albino rats weighing 250-350g underwent median laparotomy and were randomized into 3 groups: (1) sham-operated group, with no mesenteric I/R, (group I, n=12), (2) control group, with mesenteric I/R, (group II, n=12), and (3) experimental group, with mesenteric I/R but Antithrombin-III treated (group III, n=12). At the end of a six hours reperfusion period animals were killed and renal tissue samples were examined for myeloperoxidase (MPO) activity levels, and for the presence of certain types of mitochondrial lesions, both of which have been proved to be reliable indicators of the severity of local and systematic post-perfusion deleterious effects. Results: There was a significant increase in observed renal tissue mitochondrial defects (P<0.001) and MPO activity in the_I/R control group when compared with the sham operated group (P<0.001). The treatment of animals with Antithrombin-III significantly decreased the amount of mitochondrial damage (P<0.001) and MPO activity (P=0.018) compared with the control group. Conclusion: The results of the present study suggest that mesenteric ischemia and reperfusion induce renal injury. A significant attenuation of intestinal I/R-related renal injury with the use of Antithrombin-III concentrate, warrants further studies to elucidate the potential role of this natural serine protease inhibitor in clinical settings.