SSAT - THE MOLECULAR WEIGHT OF HEPARIN FRAGMENTS INTERFERES WITH THE PROTECTION OF THE HEPATOCYTE SUBJECTED TO INJURY BY ISCHEMIA AND REPERFUSION

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THE MOLECULAR WEIGHT OF HEPARIN FRAGMENTS INTERFERES WITH THE PROTECTION OF THE HEPATOCYTE SUBJECTED TO INJURY BY ISCHEMIA AND REPERFUSION
Ênio R. Vasques^*^1,2, José Eduardo M. Cunha¹, Eleazar Chaib¹, Marcelo A. Lima³, Helena Nader³, Ivarne S. Tersariol³, Luiz Augusto C. D'Albuquerque¹
¹GASTROENTEROLOGY, FMUSP, São Paulo, São Paulo, Brazil; ²RESEARCH, PREVENT SENIOR INSTITUTE, SAO PAULO, SAO PAULO, Brazil; ³BIOCHEMISTRY, UNIFESP, SAO PAULO, SAO PAULO, Brazil

Background: Calcium overload is the main factor responsible for hepatic cell death after ischemia and reperfusion (I/R). Sodium-calcium exchanger (NCX) decreases the cytoplasmic calcium levels by acceleration of calcium extrusion by means of the exchange inhibitor peptide (XIP) present in the NCX. Heparin fragments of different molecular weights interact with the XIP, changing its structure, and inhibiting the XIP function decreasing calcium content and offering cell protection. However, they have adverse effects upon the coagulation process, with the exception of the Trisulfate Disaccharide. Aims: To evaluate and compare the effects of 3 heparin fragments with different molecular weights and functions (Enoxaparin, Fondaparinux and Trisulfate Disaccharide) in the cellular protection in Wistar rats liver cells subjected to ischemia and reperfusion damage.
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. Animals were 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 groups 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 provided by these heparin fragments, with a greater effectiveness of the smaller molecular weight fragment (TD).

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