Effect of glucose on 7-hydroxycoumarin glucuronide production in periportal and pericentral regions of the liver lobule

Abstract

The effect of starvation and glucose addition on glucuronidation was assessed in sublobular regions of the lobule in perfused livers from phenobarbital-treated rats. Fibre-optic micro-light guides were placed on periportal and pericentral areas on the surface of livers to monitor the fluorescence (excitation 366 nm, emission 450 nm) of free 7-hydroxycoumarin from the tissue surface. After infusion of 7-hydroxycoumarin (80 microM) under normoxic conditions, steady-state increases in fluorescence were reached in 6-8 min in both regions. Subsequently, the formation of non-fluorescent 7-hydroxycoumarin glucuronide was inhibited completely by perfusion with N2-saturated perfusate containing 20 mM-ethanol. The difference in fluorescence between anoxic and normoxic perfusions was due to glucuronidation under these conditions. In livers from fed rats, rates of glucuronidation in periportal and pericentral regions of the liver lobule were 8 and 19 mumol/h per g, respectively. In contrast, rates of glucuronidation were 3 and 9 mumol/h per g, respectively, in periportal and pericentral regions of livers from starved rats. Infusion of glucose (20 mM) had no effect on rates of glucuronidation in livers from fed rats; however, glucose increased rates of glucuronidation rapidly (half-time, t0.5 = 1.5 min) in periportal and pericentral regions to 7 and 17 mumol/h per g, respectively in livers from starved rats. These results indicate that the rapid synthesis of the cofactor UDP-glucuronic acid derived from glucose is an important rate-determinant for glucuronidation of 7-hydroxycoumarin in both periportal and pericentral regions of livers from starved rats.

Perfusion to Colorectal Cancer Liver Metastases Is Not Uniform and Depends on Tumor Location and Feeding Vessel

“…Smaller tumors (õ2 mm) have been reported to be predominantly supplied by the porvascular distribution and not tissue perfusion. Since improving the delivery of antineoplastic agents to the tal venous system, whereas larger tumors rely almost exclusively on the hepatic artery [25,26]. This observatumor tissue has been the ultimate goal of most studies, we believe that tumor perfusion should be the pri-tion has led some investigators to use the portal vein route for infusion of adjuvant chemotherapy, where mary interest.…”

Functional Heterogeneity of Periportal and Perivenous Hepatocytes

“…Fractionation Recently, short-term (15s) digitonin perfu sion in the orthograde direction was reported to pro duce selective periportal damage, while conversely perfusion in the retrograde direction led to selective perivenous destruction [26]; after zonal damage, cell populations enriched in periportal or perivenous cells could be obtained [27,28], Ortho-and retrograde liver perfusion was used to determine the zonal localization of various processes such as urea and glutamine formation [29], glucuronidation and sulfation [30,31] ethanol metabolism [32] and oxygen consumption as linked to gluconeogenesis and glycolysis [33,34] Oxidative energy metabolism, i.e. the ini tial breakdown of fatty acids and of amino acids (but not of glucose, see below) to acetyl-CoA and the final oxidation of acetylCoA to C02, which is dependent on oxygen, is preferentially located in the 'more aerobic' periportal cells which contain the greater mi tochondrial volume and cristae area and the higher activities of key enzymes such as ß-hydroxybutyryl-CoA dehydrogenase (ß-oxi-dation), alanine aminotransferase, succinate dehydrogenase (citrate cycle) and cytochrome oxidase (respiratory chain; table II).…”

The effects of acetylsalicylic acid on phosphoenolpyruvate carboxykinase activity and acinar heterotopy in livers from juvenile and adult rats

“…Glucuronidation and sulfuronidation are processes associated to the perivenous zone (Conway et al 1985;Suolinna et al 1989). Acetylsalicilic acid is rapidly removed from the blood by deacetylation to salicylate in the liver and is then subjected to various metabolic transformations to glucuronides or sulphates (Mourelle et al 1988).…”