DISORGANIZATION OF MICROTUBULAR NETWORK IN POSTISCHEMIC LIVER DYSFUNCTION - ITS FUNCTIONAL AND MORPHOLOGICAL-CHANGES

Microtubules in the hepatocytes have been implicated to serve as lines of cytoplasmic transport of secretory materials, but are highly labil e structures sensitive to pathological conditions in the cytosol. We e xamined the role of ischemia/reperfusion-induced cytoskeletal alterati ons in postischemic liver dysfunction. Rabbit livers were subjected to 60-min warm ischemia followed by 1 h or 24 h of reperfusion. Liver fu nction was assessed by directly measuring hepatic clearance of indocya nine green (ICG), an organic anion whose cytoplasmic transport is assu med to depend on intact microtubules, using near-infrared spectroscopy . Structural alterations of microtubules were observed immunohistochem ically using tissue sections stained with monoclonal anti-beta-tubulin antibody. ICG removal from hepatocytes into bile canaliculi deteriora ted 1 h but reversed 24 h after reperfusion. Immunohistochemistry show ed fragmentation of microtubules at the end of liver ischemia. This cy toskeletal alteration was evident 1 h but was not observed 24 h after reperfusion. Treatment with prostaglandin E(1) exerted its beneficial effect by preserving ICG clearance and microtubular network. These res ults demonstrate that liver ischemia and subsequent reperfusion both a ffect the organization of microtubular network and suggest that struct ural disruption of microtubules may be a cause of postischemic liver d ysfunction.