Effect of prostaglandin F2 alpha on free radical generation, glutathione content and microsomal oxidase activities in rat liver microsomes induced either by ethanol or acetone.
We studied the effect of prostaglandin F2 alpha on parameters related to microsomal metabolism (free radical production and lipid peroxidation, glutathione content and activity of microsomal oxidases) after an induction by ethanol or acetone combined with starvation. Long-term ethanol administration led to a significant increase in lipid peroxide formation and NADPH-dependent chemiluminescence amplified by luminol and lucigenin. At the same time hydrogen peroxide production and NADPH-stimulated lipid peroxidation were enhanced although the effect did not reach the level of statistical significance. The concentration of reduced glutathione (GSH) in the liver was decreased 2-fold, whereas oxidized glutathione (GSSG) content remained unaltered. Ethanol intoxication resulted in an increase in 7-ethoxycoumarin-O-deethylase (ECOD), 7-benzyloxycoumarin-O-deethylase (BCOD) and 7-ethoxy-resorufin-O-deethylase (EROD) activities, whereas 7-pentoxyresorufin-O-deethylase (PROD) and ethylmorphin-N-demethylase (EMND) activities were unaltered. The combination of acetone treatment with starvation resulted in a significant increase in lipid and hydrogen peroxide formation, NADPH-dependent lipid peroxidation and chemiluminescence. GSH and GSSG concentration in the liver dramatically decreased 5- and 3-fold, respectively. The acetone treatment led to significant increase in EROD, ECOD, BCOD, PROD and EMND activities. The treatment of ethanol-intoxicated rats with prostaglandin F2 alpha (PGF2 alpha) exerted more pronounced prooxidant effect on liver than action of alcohol itself. At the same time, PGF2 alpha improved most of parameters changed by acetone treatment combined with starvation, decreasing lipid peroxide and radical formation and enhancing GSH and GSSG contents.
Sadovnichy
V
V
Department of Experimental Hepatology, Belarussian Academy of Sciences, Grodno, Belarus.
Müller
D
D
Buko
V
V
D000096:Acetone / Q000633:toxicity*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D013217:Starvation
D005609:Free Radicals; D000096:Acetone; D000431:Ethanol; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D015237:Dinoprost; D010088:Oxidoreductases; D005978:Glutathione