Medroxyprogesterone acetate and phenobarbital induce NADPH producing enzyme activities in rats with a chemical liver injury.
The administration of medroxyprogesterone acetate (MPA) and phenobarbital (PB) improves liver function in rats with liver damage. This was seen here as increased aryl hydrocarbon hydroxylase (AHH) activity after therapy with MPA or PB in rats with a chemical liver injury, produced by dimethylnitrosamine (DMN). Hepatic glucose-6-phosphatase (G6Pase) activity, an index of glucose metabolism was also normalized in the MPA treated rats. The present study further shows that MPA induced hepatic malic enzyme (ME) and isocitrate dehydrogenase (ICDH) activities and PB enhanced glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and ME activities in the DMN pretreated rats. This suggests that MPA and PB enhanced the capacity of altered liver tissue to generate NADPH, a cofactor in the monooxygenase system, which may, in part, enhance the restoration of drug hydroxylation in the rats. Since G6PDH, 6PGDH and ME participate in glucose metabolism, the finding that the compounds influenced these enzymes in distinct ways, may explain the different effects of MPA and PB on the restoration of glucose metabolism.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000473:pathology; D004128:Dimethylnitrosamine / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000096:biosynthesis; D007521:Isocitrate Dehydrogenase / Q000096:biosynthesis; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D008297:Male; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D009249:NADP / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D010734:Phosphogluconate Dehydrogenase / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D009249:NADP; D017258:Medroxyprogesterone Acetate; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; D005952:Glucose-6-Phosphatase; D008525:Medroxyprogesterone; D004128:Dimethylnitrosamine; D010634:Phenobarbital