PROMISING APPROACH TO LIVER PROTECTION AGAINST REPERFUSIONINDUCED INJURY

详细

全文:

Aim. To explore hepatoprotective potency of some magnesium-containing compounds of 2-aminoethanesulfonic acid on the model of ischemia/ reperfusion liver injury in experiment in rats. Material and Methods. 24 male Wistar rats, weighing 220 to 280 g, were obtained from «Stolbovaya» Animal Breeding Facility. All rats were deprived of food, but not of water, for 24 h before each experiment. The hepatic ischemia/reperfusion (I/R) protocol was performed as described previously (Harada et al., 1999). LBK-527 (100 mg/ kg) or LHT-8-16 (120 mg/kg) dissolved in saline was administered intravenously to rats (6 in each group) 30 min before reperfusion. Sham-operated animals (control-2, n=6) and naïve rats (control-1, n=6) received equal volume of saline administered the same way. Blood samples were taken from the anesthetized animals via withdrawal from the abdominal aorta using a 22-gauge needle 6 h after reperfusion to measure the level of serum alanine (AlAT) and aspartate aminotransferase (AsAT) by standard clinical automated analysis. At the same time, liver specimens were taken. Some of them stained with hematoxylin-eosin were used to assess the infiltration of polymorphonuclear leukocytes (PMNs) whereas the other samples of liver tissue were homogenized todetermine TNF-a, HGF and IL-10 level by immunoferment analysis. Results and Discussion. Intravenous administration of both substances led to decrease serum aminotransferase level in comparison with animals of control-2. Only LBK-527 had a potency to make AlAT and AsAT concentration achieve the level as that of control-1 rats. The substances, but largely LBK527 prevented activation of TNF-a-intermediated signal pathway of the organ damage whereas they increased tissue IL-10 and HGF levels, which highlighted aminoaethanesulfonate compounds protective property. Histological examination of liver specimens of pharmacologically treated rats showed weak signs of inflammatory infiltration. Conclusions. Magnesium-containing 2-Aminoaethanesulfonate compounds protected rat’s liver against ischemia/reperfusion damage. They impacted TNF-a-dependent pathway of the organ injury, prevented hepatic cytolysis via IL-10 activation, weakened liver tissue inflammation,and stimulated cells’ regeneration.