<b>MECHANISM OF LEAKAGE OF CYTOSOLIC ENZYMES FROM ANOXIC RAT LIVER CELLS: DISRUPTION OF BLEBS BY BLOOD </b><b>FLOW </b>

Abstract

During anoxic liver perfusion, numerous blebs were formed that protruded from hepatocytes, and their contents were released into the sinusoidal lumen. Cytosolic enzymes such as the cytoplasmic isozyme of aspartate aminotransferase and lactate dehydrogenase leaked into the perfusate after a lag of about 60 min, which was the time required for the formation of blebs. The leakage pattern of the enzymes was

Protection by Glycyrrhizin against Warm Ischemia‐Reperfusion–Induced Cellular Injury and Derangement of the Microcirculatory Blood Flow in the Rat Liver

“…Here, we were able to report that endothelial cell injury and hepatocyte blebbing 3 25 were early features of warm I/R‐induced injury in the rat liver. Morphologically, blebbing of the plasma membrane was recognized as an early sign of the ATP depletion that occurs during the ischemic phase 17 . Based on our observations, we suggest that the early endothelial cell injury is mediated predominantly through the mechanical forces exerted on the endothelial cells during bleb development before reperfusion.…”

“…The mitochondrial permeability transition (MPT), an increased permeability of mitochondrial membranes leading to loss of the mitochondrial membrane potential and release of the proapoptotic cytochrome c, represents a shared pathway that leads to cell death by both oncotic necrosis (oncosis) and apoptosis 17 . We observed both types of cell death of hepatocytes by morphology, TUNEL labeling, and elevated caspase‐3 activity following I/R injury.…”

“…We observed both types of cell death of hepatocytes by morphology, TUNEL labeling, and elevated caspase‐3 activity following I/R injury. Hepatocyte death can be induced either by the low flow during reperfusion due to the obstruction of sinusoids or by cytokines released from activated macrophages and leukocytes 17 .…”

“…The observed reduction in sinusoidal perfusion may be due to obstruction of the sinusoids by entrapped blood cells or thrombotic material, in addition to the development of swollen perisinusoidal cells. It has been known for some time that hypoxia‐induced disruption to the hepatocyte membrane and cytoskeleton causes hepatocyte blebbing 12 , where portions of the hepatocyte protrude into the lumen of the sinusoid, which, in turn, could then reduce blood flow in the microcirculation 17 3 25 . How the hepatocyte blebs develop in vivo and how they might contribute to the subsequent disruption of microcirculatory perfusion and the development of hepatocellular injury is unknown.…”