Effects of the administration of anticoagulants on the activity of the enzyme-reduced NAD(P)H dehydrogenase in rat livers, hepatomas and precarcinomatous rat liver lesions.
The anticoagulants dicumarol, warfarin and diphenadione, are in vitro inhibitors of the enzyme reduced NAD(P)H dehydrogenase of rat liver. These chemicals were administered by intragastric gavage to determine whether the same inhibitory effects could be observed in Sprague-Dawley male rats. Doses of 2 and 10 mg/100 g body weight were used. Our results indicate that only dicumarol inhibited the enzyme, whereas warfarin did not produce a significant effect, and diphenadione at large doses produced an increase in the activity of the enzyme. Dicumarol was further tested to see if it would alter the activity of the enzyme in hyperplastic nodules and liver hepatomas. A similar inhibitory effect was found. The three strains of rats tested in this work have different levels of reduced NAD(P)H dehydrogenase activity. Thus, our results indicate that dicumarol is the only anticoagulant that inhibits in vivo the reduced NAD(P)H dehydrogenase of rat liver and liver neoplasms.
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001728:Dicumarol / Q000494:pharmacology; D006965:Hyperplasia; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone); D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010630:Phenindione / Q000031:analogs & derivatives / Q000494:pharmacology; D011230:Precancerous Conditions / Q000201:enzymology*; D011808:Quinone Reductases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; C100262:diphenadione; D010630:Phenindione; D014859:Warfarin; D001728:Dicumarol; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases