ABSTRACT
Ischemia reperfusion injury [IRI] is a multifactorial process that may be the main underlying factor in critical phases faced during and after liver transplantation. This work evaluates the effect of methylprednisolone [MP] and prostaglandin El [PGE1] on IRI of the liver of dogs at the ultrastructural level together with the assessment of soluble P-and E- selectin levels. Three groups of dogs [9 each] were subjected to 60 min ischemia followed by 30 min reperfusion with the appropriate solution according to the group. Group I, the control untreated group was flushed with Ringer's solution, group II was administered 10 mg/kg MP 24 hours before the procedure and with induction of anaesthesia, and group III was flushed with PGE1 in Ringer's solution at a rate of 0.02 microg/kg/min. Liver specimens were collected before ischemia, after ischemia and after reperfusion and were processed for the preparation of ultrathin sections for electron microscopic examination. Corresponding venous blood samples were harvested, centrifuged and serum was processed for the estimation of soluble P-and E- selectins by enzyme immunoassay, together with alanine and aspartate aminotransferases. Electron microscopic [EM] examination of liver ultrathin sections revealed that the morphological structure of hepatocytes and endothelial lining of hepatic sinusoids were well preserved in the group treated with PGE1. Hepatic ultrastructure was much altered in MP treated group showing necrotic and degenerative changes. The control untreated group disclosed bleb formation of hepatocytic membrane with increased leukocyte infiltration. Soluble P-and E- selectin levels were significantly elevated in the control group, near to pre-ischemic level in PGE1 group and showed a persistent elevation in MP group. Serum transaminases [AST and ALT] were significantly elevated in both control and MP groups as compared to their corresponding pre-ischemic levels. Yet, in PGE1 group, their values were comparable to the pre-ischemic ones. This work confirms the hepatoprotective effect of PGE1 in IR injury. The PGE1 impact on preserving the subcellular structure of hepatic sinusoids is crucial and may be mainly attributed to its biological properties. We presume that P-and E- selectins are greatly implicated in the mechanism of IR and may be an important therapeutic target by specific monoclonal antibodies