Effect of aeration on the consumption of ethanol by the isolated perfused rat liver.
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Animals↗
Biomedical subjects
E R Gordon
Publications and source records attributed to E R Gordon.
Biochemical and morphological alterations of baboon hepatic mitochondria after chronic ethanol consumption.
Baboons fed ethanol (50% of total calories) chronically develop ultrastructural alterations of hepatic mitochondria. To determine whether mitochondrial functions are also altered, mitochondria were isolated from nine baboons fed ethanol chronically and their pair-fed controls. At the fatty liver stage, ADP-stimulated respiration was depressed in ethanol-fed baboons by 59.4% with glutamate, 43.2% with acetaldehyde, 45.1% with succinate and 51.1% with ascorbate as substrates. A similar decrease was noted in the ADP/O ratio (14 to 28%) and respiratory control ratio (20 to 44%) with all substrates. Similar alterations of mitochondrial functions were observed in baboons with more advanced stages of liver disease, namely fibrosis. These changes after ethanol treatment were associated with decreases in the enzyme activities of mitochondrial respiratory chain: glutamate, NADH and succinate dehydrogenase (42, 24 and 28%, respectively), glutamate-, NADH- or succinate-cytochrome c reductase (42, 27 and 32%, respectively) and cytochrome oxidase (59.6%). The content of all cytochromes was also decreased in ethanol-fed baboons, especially aa3 (57%). Moreover, [14C]leucine incorporation into mitochondrial membranes was depressed by 21% after ethanol treatment. On the other hand, glutamate dehydrogenase activities of serum and cytosol in ethanol-fed baboons were significantly higher than those in pair-fed controls. Morphologically, mitochondria of ethanol-fed baboons were larger than those of pair-fed controls. However, the mitochondrial protein content per mitochondrial DNA was unchanged. From these results, we conclude that, morphologically and functionally, hepatic mitochondria in baboons are altered by chronic ethanol consumption; it is noteworthy that these changes are fully developed already at the fatty liver stage, and that morphological alteration appears to reflect the damage of mitochondrial membranes rather than an adaptive hypertrophy.
Alcoholism↗
The effect of changes in the fluid state of rat liver plasma membrane on the transport of taurocholate.
The fluidity of basolateral and canalicular rat liver plasma membranes was compared with respect to their response to the membrane perturbants ethanol and calcium. The relation between membrane fluidity and taurocholate transport, a liver plasma membrane function mediated by carrier proteins, was also examined. Membrane fluidity was measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as a probe. Uptake of [3H]taurocholate into basolateral rat liver plasma membrane and canalicular rat liver plasma membrane vesicles was measured by a rapid Millipore filtration technique. Anisotropy values were found to be significantly lower for the basolateral rat liver plasma membrane (0.2287 +/- 0.0014) than for the canalicular rat liver plasma membrane (0.2612 +/- 0.0012), indicating that basolateral rat liver plasma membranes are more fluid than canalicular rat liver plasma membranes. Ethanol produced a concentration-dependent effect on lipid fluidity and inhibition of taurocholate uptake, in both membrane preparations. Pretreatment of the membrane with calcium increased the rigidity of both membrane preparations. However, the change in the anisotropy with calcium was only slight in the more rigid canalicular rat liver plasma membrane, while the change in anisotropy was greater and associated with a decrease in taurocholate uptake in the basolateral rat liver plasma membrane. Both the effects of ethanol and calcium were more pronounced in basolateral rat liver plasma membrane than in canalicular rat liver plasma membrane. These results indicate that the fluid state of the hydrophobic bilayer of liver plasma membrane lipids play an important role in regulating bile acid transport in both sinusoidal and canalicular domains.
Animals↗
Metabolic state of the rat liver with ethanol: comparison of in vivo 31phosphorus nuclear magnetic resonance spectroscopy with freeze clamp assessment.
In vivo 31phosphorus nuclear magnetic resonance spectroscopy was used to measure the hepatic metabolic state in various groups of rats given ethanol, a control liquid diet or a solid chow diet. The use of selective presaturation pulses applied to the broad phosphorus resonances of immobile phospholipids permitted reliable determination of ATP/ADP ratios by quantitation of the ATP-beta and ATP-gamma peak areas. ATP/ADP ratios were depressed by both techniques in rats chronically ingesting ethanol compared to pair-fed animals consuming the control liquid diet. These differences were observed regardless of whether ethanol feeding was continued up to the time of investigation or whether it was discontinued for 24 hr prior to study. Acute alcohol administration in chow-fed rats, not previously ingesting ethanol, did not lower hepatic ATP/ADP ratios by either methodology. In all cases, liver ATP/ADP ratios assessed by 31phosphorus nuclear magnetic resonance spectroscopy were higher than those measured by high-performance liquid chromatography. However, parallel decreases in hepatic ATP/ADP ratios were observed with chronic ethanol consumption by both 31phosphorus nuclear magnetic resonance spectroscopy and the biochemical method, confirming the utility of in vivo 31phosphorus nuclear magnetic resonance spectroscopy for assessment of the hepatic bioenergetic status. The difference in absolute ATP/ADP ratios by the two methods may to some degree be explained by binding effects of ADP with proteins or mitochondrial membranes, rendering it partially invisible to nuclear magnetic resonance or alternatively, by breakdown of high energy phosphate bonds with freeze clamp extraction.
Adenosine Diphosphate↗
Microsomal specificity underlying the differing hepatic formation of bilirubin glucuronide and glucose conjugates by rat and dog.
Bilirubin monoglucuronide monoglucoside diester is one of the principal bilirubin conjugates in dog bile (and a lesser conjugate, in human bile), and bilirubin diglucoside is an occasional trace conjugate in dog bile whereas, in contrast, neither is detectable in rat bile. In order to investigate, in comparative fashion, the factors underlying the formation of glucuronide and glucose-containing conjugates, hepatic microsomes were isolated by differential centrifugation from the livers of both normal mongrel dogs and Sprague-Dawley rats, and their formation of bilirubin conjugates examined, in the presence of varying levels of UDP-glucuronate and UDP-glucose. Bilirubin and its conjugates were extracted and separated by high-performance liquid chromatography; a new methodology was devised, which clearly separates bilirubin diglucoside from bilirubin monoglucuronide, as well as bilirubin diglucuronide, the mixed monoglucuronide monoglucoside conjugate and bilirubin monoglucoside. At bilirubin levels of 12.5 microM, in the presence of equal amounts of both UDP-glucuronate and UDP-glucose, dog microsomes formed substantial amounts of both bilirubin diglucuronide and the mixed monoglucuronide-monoglucoside conjugate, and minor amounts of bilirubin monoglucuronide and bilirubin diglucoside. Microsomes from rat liver, under similar conditions, formed only bilirubin diglucuronide and bilirubin monoglucuronide. When only UDP-glucose was present, dog microsomes formed predominantly diglucoside and rat, predominantly monoglucoside. The findings imply that it is not the availability of the UDP-glycoside but rather the preference of the microsomal enzymic system for the different glycosidic nucleotides which dictates the varieties of bilirubin conjugates ordinarily formed in these two species.
Animals↗
The effect of ethanol and calcium on fluid state of plasma membranes of rat hepatocytes.
Basolateral (blLPM) and canalicular (cLPM) plasma membrane vesicles were isolated from rat liver to compare membrane fluidity, fluidity responses to membrane perturbants, and the relationship between fluidity and a membrane protein function such as carrier-mediated taurocholate transport. Membrane fluidity was measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as a probe. Uptake of [3H] taurocholate was measured by a rapid Millipore filtration technique. blLPM were more fluid than cLPM. Ethanol produced a concentration-dependent fluidizing effect on both membrane preparations, the change being greater in blLPM. Incubation with calcium for 2 hr at 37 degrees C rendered both membrane preparations more rigid, again the cLPM being more resistant to perturbation. There was a linear correlation between an increase in membrane fluidity and inhibition of taurocholate uptake into blLPM in the presence of increasing concentrations of ethanol. The data support the concept that membrane lipid fluidity is an important regulator of membrane protein functions and hence also of overall cellular activity.
Animals↗