Glycohydrolases As Markers of Hepatic Ischemia–Reperfusion Injury and Recovery

Abstract

ism itself. A number of hypotheses have been articulated to Advances in liver surgery and transplantation have provide mechanistic explanations for reperfusion injury: free lead to a steady increase in the number of these interradical generation and attack of unsaturated lipids, proteins, ventions. Prompt quantitative assessment of hepatic and nucleic acids; increased turnover of membrane phosphofunction and a patient's subsequent morbidity and morlipids; and disturbances of calcium homeostasis at the cellutality following surgery remain difficult despite the curlar level. The liver is one of the organs that is most sensitive to hepatic ischemia, the systemic release of eight different ischemia. [5][6][7] Advances in liver surgery and liver transplantaglycohydrolases and lipid peroxides into serum were de-tion in particular have stimulated the search for quantitative termined and compared with pre-and postischemic se-biochemical markers that would provide surgeons and clinirum levels of LDH, GGT, and AST. The rapid release of cians with a means of assessing objectively and expeditiously glycohydrolases into serum was directly proportional to the functional integrity of the liver after various surgeries the length of the ischemic period from 30 to 90 minutes have been performed, in particular those which require iso-(e.g., b-glucosidase, mean 1.9-fold increase at 30 minutes; lating the organ from its normal blood supply for significant 8.3-fold at 45 minutes; and 22.8-fold at 90 minutes; P õ periods of time. The enzymes that have been used historically .002) and the activities peaked within the first 3 hours' and which are still relied upon today to monitor liver function postischemia. In contrast, AST, LDH, and GGT were re-postsurgically, include lactate dehydrogenase (LDH), g-gluleased slowly and peaked 20 to 30 hours after hepatic tamyl transpeptidase (GGT), and aspartate transaminase blood flow was restored. In swine with fatal outcomes (AST). Increased plasma activities of a number of glycohydro-(90 minutes of ischemia), all enzyme levels increased lases have been found to result from a variety of liver injuries, continuously during the final hours of life. However, in including: carbon tetrachloride-induced liver cirrhosis, 8 parswine that survived hepatic ischemia/reperfusion injury tial hepatectomy, 9,10 hepatic dearterialization, 11 hepatic cryo-(45 minutes of ischemia) the glycohydrolases, but not surgery, 12 and cold and warm hepatic ischemia. [13][14][15] Free radi-AST, LDH, and GGT, declined after 2 to 3 hours' postisch-cals produced by liver injury are thought to be the mediators emia and the serum lipid peroxide levels followed the responsible for hepatic damage and have been described in same pattern. Serum b-galactosidase and b-glucosidase many animal models. 6,7,16-18 In 1991, Chang et al. 19 reported levels are sensitive markers that rise as quickly as tradi-that following liver transplantation in the pig the activity tional enzyme markers (AST, LDH, GGT) following he-levels of several glycohy...

Expression of cytosolic β-glucosidase in guinea pig liver cells

“…Chang et al 17 described rapid release of ␤-glucosidase from pig liver following transplantation-induced ischemic liver injury. Liu et al 16 confirmed this observation, and established that the cytosolic isoform is the major ␤-glucosidase released. They further demonstrated that elevations in cytosolic ␤-glucosidase were diagnostic of fatal versus nonfatal liver injury.…”

“…27 Based on the results of Liu et al, 16 we hypothesized that cytosolic ␤-glucosidase is expressed predominantly by Kupffer cells. We therefore expected to find a several-fold increase in the specific activity of cytosolic ␤-glucosidase in the enriched NPC fraction after collagenase perfusion of the liver.…”

“…Based on the correlations between ␤-glucosidase levels and lipid peroxidation products, Liu et al speculated that cytosolic ␤-glucosidase might be released from Kupffer cells activated by reperfusion injury. 16 We have investigated the expression of cytosolic ␤-glucosidase in guinea pig liver by a variety of methods. We found that the enzyme is expressed almost exclusively in hepatocytes and not in nonparenchymal cells (NPCs); that different…”

“…15 More significantly, these investigators found that amygdalin and vicine were transported intact across the intestinal mucosa in vitro, thus demonstrating that these potential substrates could be presented to the liver via the portal circulation for hydrolysis by cytosolic ␤-glucosidase. 15 Recently, Liu et al 16 reported that, in a swine model of warm ischemic liver injury, cytosolic ␤-glucosidase was an earlier marker of liver injury than aspartate transaminase, ␥-glutamyl transpeptidase, or lactate dehydrogenase (LDH). Similar to an earlier report by Chang et al, 17 the activity of cytosolic ␤-glucosidase in the hepatic vein peaked at 3 hours' postreperfusion, with a 23-fold elevation.…”

“…Based on the correlations between ␤-glucosidase levels and lipid peroxidation products, Liu et al speculated that cytosolic ␤-glucosidase might be released from Kupffer cells activated by reperfusion injury. 16 We have investigated the expression of cytosolic ␤-glucosidase in guinea pig liver by a variety of methods. We found that the enzyme is expressed almost exclusively in hepatocytes and not in nonparenchymal cells (NPCs); that different ␤-D-glucosides are taken up from the extracellular fluid and hydrolyzed by cytosolic ␤-glucosidase in cultured cells and in tissue slices; and that lethal cell injury in vitro results in the release of cytosolic ␤-glucosidase into the extracellular fluid.…”