Liver inducing system

Disulfoton induced the liver MFO system in animals (Stevens et al. 1973). In the same study, exposure to disulfoton orally for 3 days also increased ethylmorphine N-demethylase and NADPH oxidase activities, but had no effect on NADPH cytochrome c reductase. Thus, the induction of the MFO system required repeated dosing with relatively high doses. Furthermore, these changes are not specific for disulfoton exposure, and these subtle liver effects require invasive techniques in humans to obtain liver tissue for performance of these enzyme assays. 

Each term with a metabolic component (Fgm, Fh, CL) is a function of unbound fraction in blood (/ ) and intrinsic clearance (i.e., Emax/Km in biochemical terms) and can be modified by an enzyme/transporter inducer or inhibitor. If chug is completely absorbed and elimination occurs exclusively in the liver, the systemic AUC observed in the presence of a metabolic modulator would directly reflect... 

Kettaneh A, Fain O, Ziol M, Lejeune F, Eclache-Saudreau V, Biaggi A, Guettier-Bouttier C, Thomas M. Minocychne-induced systemic adverse reaction with liver and bone marrow granulomas and Sezary-hke cells. Am J Med 2000 108(4) 353-4. 

Inflammatory conditions of the liver, in particular inflammatory hepatocellular cholestasis, are one of the most frequent causes of jaundice in the clinic. The major underlying denominator of this disorder is the inhibition of transporter expression and function by proinflammatory cytokines, which are either induced systemically or within the liver. Alcoholic hepatitis accounts for up to two-thirds of patients and is the most frequent trigger, followed by idiosyncratic drug reactions, sepsis or other extrahepatic bacterial infections, some variants of viral hepatitis, and total parenteral nutrition [95, 96]. 

Experiments with cats showed that propylthiouracil induces systemic lupus erythematosus-like phenomena (autoantibodies against nuclear antigen, Smith [Sm] antigen, red blood cells, and cytoplasmic components, lymphoadenopathy, weight loss) (Aucoin, 1989). However, important propylthiouracil-induced symptoms, such as agranulocytosis and liver toxicity, observed in humans are... 

DNA damage and metal tissue concentration was observed for lung, liver, and kidney. These results show that lead inhalation induces systemic DNA damage, but that some organs (e.g., lung and liver) are special targets of this metal. The damage is dependent in part on the duration of expo-... 

First-pass acetylation in the Gl mucosa and liver is related to genetic acetylator phenotype (8). Acetylation phenotype is an important determinant of the plasma concentrations of hydralazine when the same dose of hydralazine is administered orally. Slow acetylators have an autosomal recessive trait that results in a relative deficiency of the hepatic enzyme N-acetyl transferase, thus prolonging the elimination half-life of hydralazine (see Chapter 10). This population of hypertensive patients will require an adjustment in dose to reduce the increased overactive response. Approximately 50% of African Americans and Caucasians, and the majority of American Indians, Eskimos, and Orientals are rapid acetylators of hydralazine. This population of patients will have subtherapeutic plasma concentrations of hydralazine because of its rapid metabolism to inactive metabolites and shorter elimination times. Patients with hydralazine-induced systemic lupus erythematosus frequently are slow acetylators. 

Zinc is another essential metal, a cofactor to many metalloenzymes. Its deficiency can induce effects on liver, nervons system, eye, skin and testis. Excessive intake of this metal, however, may prodnce adverse effects. The toxicity of the metal from ingestion is relatively low as it is readily excreted. Chronic exposure to the fume, however, may lead to metal fume fever, which could probably be attributed to the bivalent zinc ion, Zn +. Althongh the metal in its zero-valent state exhibits little inhalation toxicity, in its oxidation state or as oxide it can present a serions health hazard. Inhalation of Zn2+ or metal oxide fnme can prodnce a sweet metallic taste, congh, chills, fever, dry throat, nansea, vomiting, blnrred vision, ache, weakness, and other symptoms. The nontoxic fnme of the metal is snsceptible to oxidize in the air in the presence of moistnre and in contact with many other snbstances in air. The metal powder or its dnst is a skin irritant. 

Graham WGB, Dundas GR (1979) Isoniazid-related liver disease occurrence with portal hypertension, hypoalbuminemia and hypersplenism. JAMA 1242 353 Greenberg J, Usar MC, Lutcher CL (1972) Drug-induced systemic lupus erythematosus. JAMA 222 191... 

IV. SOME PROPERTIES OF THE INDUCING SYSTEM OF ALA-SYNTHETASE IN LIVER... 

De Matteis F (1988) Role or iron in the hydrogen peroxide-dependent oxidation of hexahydroporphyrins (porphyrinogens) a possible mechanism for the exacerbation by iron of hepatic uroporphyria. Mol Pharmacol 33 463-469 De Matteis F, Harvey C, Reed C, Hempenius R (1988) Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Biochem J 250 161-169... 

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