The Molecular weight of heparin fragments interferes with the protection of the hepatocyte subjected to injury by ischemia and reperfusion

Abstract

Background: Calcium overload is responsible for hepatic cell death after ischemia and reperfusion (I/R). Sodium-calcium exchanger (NCX) decreases the cytoplasmic calcium by acceleration of calcium extrusion. Heparin fragments of different molecular weights interact with the NCX decreasing calcium. However, they have adverse effects upon the coagulation process, except Trisulfate Disaccharide(TD). Aims: To evaluate and compare the effects of heparin fragments with different molecular weights in the cellular protection in Wistar rats liver cells subjected to ischemia and reperfusion. Materials and methods: Male Wistar Rats were subjected to surgical ischemia of the median and lateral liver lobes for 60 minutes and reperfusion for 4 hours and divided in 4 Groups (n=6): Control: IV infusion of saline; Enox: Enoxaparin (4200 Da) IV infusion (2mg/kg); Fond: Fondaparinux (3000 Da) IV infusion (0.03 mg/Kg); TD: Trisulfate Disaccharide (585 Da) IV infusion (0.2 mg/kg). Saline or heparin fragments (0.4 ml) were injected into the penile vein, 10 minutes before reperfusion. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) were quantified after 4h of Reperfusion. Results: There were decreases in ALT and AST in Enox, Fond and TD when compared with the control group (p < 0.05). There was no difference between Enox and Fond groups, but TD group animals presented lower ALT levels compared to Enox and Fond groups. Conclusion: Decreased ALT and AST levels after administration of Enoxaparin, Fondaparinux and Trisulfate Disaccharide in the animal model of liver I/R suggests hepatocellular protection with a greater effectiveness of the smaller molecular weight fragment (TD).