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Antioxidative effect of prostaglandin E1 in chronic alcohol intoxication
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EFA & Eicosanoids 1997 - Edinburgh
Poster Presentations Tuesday 22 July
Pl19
P120
ANTIOXIDATIVE EFFECT OF PROSTAGLANDIN E l IN CHRONIC ALCOHOL INTOXICATION Buko V., Sadovnichy V., Maltsev A., Lukivskaya O. Institute of Biochemistry, 230017 Grodno, Belams
BENEFITIAL EFFECT OF PROSTAGLANDIN E2 AND cAMP-DEPENDENT SIGNAL TRANSDUCTION IN EXPERIMENTAL ALCOHOLIC LIVER INJURY Buko V., Maltsev A., Institute of Biochemistry, 230017 Grodno, Belarus.
The contribution of free radicals and products of lipid peroxidation in alcoholic liver injury has been actively discussed. We studied the effects of prostaglandin (PG) E] having hepatoprotective properties on flee oxygen radicalrelated parameters and lipid peroxidation in the liver of rats treated wit ethanol (5 g/kg b.w., i.g., 56 days). Chronic alcohol intoxication increased microsomal NADPH oxidation, cytochrome P-450 content, activity of inicrosomal ethanoloxidizing system (MEOS) and NADPH-stimulated chemilunfiniseense of microsomes attenuated by luminol and lucigenin. Ethanol also raised superoxide dlSmutase (SOD) activity in liver microsomes, increased the content of liver malondialdehyde (MDA) and other carbonyl-containing compounds (polar carbonyls, a!kanals , ozazones, hydroxyalkenals). PGE1 (4 mg/kg, i.p., the last 10 days) nommlized cytochrome P-450 content, NADPH oxidase and MEOS activities, NADPH-induced chenfiluminiscence attenuated by luminol and SOD activity in the liver of alcoholtreated rats. PGE1 decreased liver carbonyls and MDA content elevated by ethanol. We proposed that tile antiradical and antioxidative effects of PGEl are realized via nomlalization of the parameters related to cytochrome P-450 which is the main source of free oxygen radicals in the liver. We suggest that antiradical and antioxidative effects of PGEI play an impol~tant role in the hepatoproteetion by this natural metabolite.
We studied the morphological and metabolic changes in the liver of rats with alcoholic fatty liver and their correction by PGE~. Chronic alcohol imoxication (CA[) (5 g/kg, i.g., 40 days) was accompanied by EFA deficiency which, in turn, led to a decrease of the PG synthase activities and PG level in the liver. We showed liver fatty and hydropic dystrophy as well as increased tliglycelide content and serum marker enzylnes activity in ethanol-treated rats. CAI activated liver adenylate cyclase and protein kinase A and enhanced cAMP content. The PGE2 treatment (4 mg/kg, i.p., the last 10 days) of rats with CA[ improved the liver molphological picture, decreasing fatty infiltration in peripox-tal zone and vacuolization of hepatocytes, normalized serum and liver triglycerides and serum marker enzyme activities. PGE2 decreased protein kinase A activity whereas epinephrine-stimulated adenylate cyclase activity was significantly increased compared to the ethanol-treated group. Earlier we showed that the decrease of tile PGE content promoted the alkylation of rat liver PGE receptors, decreasing receptor density (Buko & Zavodnik, 1990). Tile cAMPdependent signal transduction from PGE receptors to protein kinase A was disturbed in this way in CAl. We suggest that disturbances in liver enzyme phosphorylationdephospholylation by cAMP-stimulated protein kinase A may alter cell metabolism that probably are one of the liver damaging factors in CAI whereas the hepatoprotective effect of PGE2 can be realized due to the con'ection of these changes.
EFA & Eicosanoids 1997 - Edinburgh
Poster Presentations Tuesday 22 July
Pl19
P120
ANTIOXIDATIVE EFFECT OF PROSTAGLANDIN E l IN CHRONIC ALCOHOL INTOXICATION Buko V., Sadovnichy V., Maltsev A., Lukivskaya O. Institute of Biochemistry, 230017 Grodno, Belams
BENEFITIAL EFFECT OF PROSTAGLANDIN E2 AND cAMP-DEPENDENT SIGNAL TRANSDUCTION IN EXPERIMENTAL ALCOHOLIC LIVER INJURY Buko V., Maltsev A., Institute of Biochemistry, 230017 Grodno, Belarus.
The contribution of free radicals and products of lipid peroxidation in alcoholic liver injury has been actively discussed. We studied the effects of prostaglandin (PG) E] having hepatoprotective properties on flee oxygen radicalrelated parameters and lipid peroxidation in the liver of rats treated wit ethanol (5 g/kg b.w., i.g., 56 days). Chronic alcohol intoxication increased microsomal NADPH oxidation, cytochrome P-450 content, activity of inicrosomal ethanoloxidizing system (MEOS) and NADPH-stimulated chemilunfiniseense of microsomes attenuated by luminol and lucigenin. Ethanol also raised superoxide dlSmutase (SOD) activity in liver microsomes, increased the content of liver malondialdehyde (MDA) and other carbonyl-containing compounds (polar carbonyls, a!kanals , ozazones, hydroxyalkenals). PGE1 (4 mg/kg, i.p., the last 10 days) nommlized cytochrome P-450 content, NADPH oxidase and MEOS activities, NADPH-induced chenfiluminiscence attenuated by luminol and SOD activity in the liver of alcoholtreated rats. PGE1 decreased liver carbonyls and MDA content elevated by ethanol. We proposed that tile antiradical and antioxidative effects of PGEl are realized via nomlalization of the parameters related to cytochrome P-450 which is the main source of free oxygen radicals in the liver. We suggest that antiradical and antioxidative effects of PGEI play an impol~tant role in the hepatoproteetion by this natural metabolite.
We studied the morphological and metabolic changes in the liver of rats with alcoholic fatty liver and their correction by PGE~. Chronic alcohol imoxication (CA[) (5 g/kg, i.g., 40 days) was accompanied by EFA deficiency which, in turn, led to a decrease of the PG synthase activities and PG level in the liver. We showed liver fatty and hydropic dystrophy as well as increased tliglycelide content and serum marker enzylnes activity in ethanol-treated rats. CAI activated liver adenylate cyclase and protein kinase A and enhanced cAMP content. The PGE2 treatment (4 mg/kg, i.p., the last 10 days) of rats with CA[ improved the liver molphological picture, decreasing fatty infiltration in peripox-tal zone and vacuolization of hepatocytes, normalized serum and liver triglycerides and serum marker enzyme activities. PGE2 decreased protein kinase A activity whereas epinephrine-stimulated adenylate cyclase activity was significantly increased compared to the ethanol-treated group. Earlier we showed that the decrease of tile PGE content promoted the alkylation of rat liver PGE receptors, decreasing receptor density (Buko & Zavodnik, 1990). Tile cAMPdependent signal transduction from PGE receptors to protein kinase A was disturbed in this way in CAl. We suggest that disturbances in liver enzyme phosphorylationdephospholylation by cAMP-stimulated protein kinase A may alter cell metabolism that probably are one of the liver damaging factors in CAI whereas the hepatoprotective effect of PGE2 can be realized due to the con'ection of these changes.