Influence of liver function and alcohol dehydrogenase activity on ethanol metabolism in chronic alcoholics

Influence of liver function and alcohol dehydrogenase activity on ethanol metabolism in chronic alcoholics

EICOSANOID PRODUCTION BY RAT KUPFFER CELLS AND RAT AND HUMAN PERITONEAL MACROPHAGES 241 R.J.T. Ouwendijk, F.J. Zijlstra~ A. van den Broek t A. Brouwe...

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EICOSANOID PRODUCTION BY RAT KUPFFER CELLS AND RAT AND HUMAN PERITONEAL MACROPHAGES 241

R.J.T. Ouwendijk, F.J. Zijlstra~ A. van den Broek t A. Brouwer~ J.E. Vincent, J.H.P. Wilson. Depts. of Internal Medicine and Pharmacology, Erasmus University, Rotterdam and Institute for Experimental Gerontology, Rijswijk, the Netherlands. To determine whether there are species and tissue differences in eicosanoid production by macrophages, we examined the metabolism of arachidonate in human ascites cells, rat peritoneal macrophages and rat kupffer cells. Human and rat peritoneal macrophages were isolated by centrifugation, rat kupffer cells by elutriation. The cells were labelled with ]4C-arachidonic acid and stimulated with the calcium ionophore A23187. The metabolites formed were separated by high pressure liquid chromatographD Human peritoneal macrophages formed mainly leukotriene B4, 5~hydroxy-6,8,11,14 eicosatetraenoic acid and leukotriene C4 and smaller amounts of thromboxane B2, 12-hydroxy-5,8,10 heptadecatrienoic acid and 6-keto-prostaglandin Flalpha , whereas rat peritoneal macrophages mainly produce cyclooxygenase products, especially thromboxane B 2 and ]2-hydroxy-5,8,10 heptadecatrienoic acid. The rat kupffer cells also mainly synthesize cyclooxygenase products, but in contrast to the peritoneal macrophages these are prostaglandin F2alpha, prostaglandin D2 and prostaglandin E 2. Conclusion: The profile of eicosanoids produced by macrophages is dependent both on the species and on the tissue from which the macrophage is derived. This probably influences macrophage function in vivo.

INFLUENCE OF LIVER FUNCTION AND ALCOHOL DEHYDROGENASE ACTIVITY ON ETHANOL METABOLISM IN CHRONIC ALCOHOLICS. J. Pan~s, A. Par~s, X. Par~s, M. Rodamilans, J. Caballerfa, X. Soler, R. Guitart 242 and J. Rod's. Liver Unit and Laboratory of Toxicology. Hospital Clinic i Provincial. Universitat de Barcelona. Department of Biochemistry. Facultat de Ci~ncies. Universitat AutSnoma de Barcelona. Bellaterra. Spain We have investigated the relationship between ethanol metabolism, alcohol dehydrogenase activity (ADH) and liver function in chronic alcoholics. Fifteen recently alcohol drinkers without clin~caal manifestations of liver d i s ~ s e were studied. Liver function was evaluated by and oral --C-aminopyrine breath-test (BT---C). Ethanol metabolic rate (EMR) was measured after venous infusion of 1 g ethanol per kg body weight, according to the Widmark's method. A Tru-Cut needle biopsy was performed and the sample obtained was used for histological analysis and for determinations of ADH activities at pH 7 and pH 10.5. Patients were divided in two groups according to the histological diagnosis: i0 had minimal changes or fatty liver (group A) and 5 ~ d alcoholic hepatitis or cirrhosis (group B). There were marked differences in the EMR, BT---C and in ADH activities between both groups. group A group B EMR.~mg/kg/h) 125.2 + 5.2 100.3 + 5.8 p
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