Cytochrome P-450 and hepatic drug biotransformation during progressive cardiac disease in cardiomyopathic hamsters

1979 ◽  
Vol 57 (3) ◽  
pp. 302-304 ◽  
Author(s):  
Kenneth W. Renton ◽  
James C. Baker ◽  
Leslie E. Bailey
Keyword(s):  
Heart Failure ◽  
Cardiac Disease ◽  
Disease Process ◽  
Microsomal Protein ◽  
Hepatic Drug ◽  
Drug Biotransformation ◽  
Hepatic Microsomes ◽  
Cardiomyopathic Hamsters ◽  
Demethylase Activity ◽  
Cytochrome P 450

Reductions in cytochrome P-450 levels and aminopyrine N-demethylase activity of hepatic microsomes obtained from cardiomyopathic hamsters (BIO 14.6) occurred at all stages of the disease before the development of congestive heart failure (CHF). Cytochrome b5 levels were reduced only in animals with CHF when compared with age-matched controls (BIO.RB). Total microsomal protein and p-nitrophenol glucuronidation were not affected by the disease process. We conclude that the reduction in cytochrome P-450 levels and N-demethylase activity in cardiomyopathic hamsters is not a consequence of CHF, but is one of the manifestations of the disease process.

scholarly journals High activity of cytochrome P-450-linked aminopyrine N-demethylase in mouse brain microsomes, and associated sex-related difference

1989 ◽  
Vol 261 (3) ◽  
pp. 769-773 ◽  
Author(s):  
V Ravindranath ◽  
H K Ananda Theertha Varada
Keyword(s):  
Mouse Brain ◽  
Male Mouse ◽  
Mouse Liver ◽  
Double Diffusion ◽  
Microsomal Protein ◽  
Cross Reactivity ◽  
Related Difference ◽  
Brain Microsomes ◽  
Demethylase Activity ◽  
Cytochrome P 450

The presence of cytochrome P-450 and associated mono-oxygenase activities was examined in brain microsomes from male and female mice. Although the cytochrome P-450 level in male mouse brain was very low as compared with mouse liver, the aminopyrine N-demethylase and morphine N-demethylase specific activities in male mouse brain were much higher than those observed in mouse liver. Ethoxycoumarin O-de-ethylase and aniline hydroxylase activities were, however, not detected in mouse brain. Sex-related differences were observed in both the cytochrome P-450 levels and aminopyrine N-demethylase activity in mouse brain, the levels of both being higher in male mouse brain as compared with female mouse brain. Aminopyrine N-demethylase activity in mouse brain microsomes was dependent on the presence of oxygen and NADPH and could be inhibited by piperonyl butoxide, N-octyl imidazole and carbon monoxide. Antiserum raised to the phenobarbital-inducible form of rat liver cytochrome P-450 [P-450(b+e)] inhibited mouse brain aminopyrine N-demethylase activity by around 80+ mouse brain microsomal protein exhibited cross-reactivity against this antiserum when examined by Ouchterlony double diffusion and immunoblotting. The present results indicate the presence of a phenobarbital-inducible form of cytochrome P-450 (or a form of cytochrome P-450 that is similar immunologically) in mouse brain microsomes, which is associated with a sex-related difference.

Inhibition of the synthesis of hepatic cytochrome P-450 by the interferon-inducing agent poly rI.rC

1984 ◽  
Vol 62 (4) ◽  
pp. 379-383 ◽  
Author(s):  
Gurmit Singh ◽  
Kenneth W. Renton
Keyword(s):  
Amino Acids ◽  
Gel Filtration ◽  
Deae Cellulose ◽  
Microsomal Protein ◽  
Interferon Inducer ◽  
Molecular Weights ◽  
Drug Biotransformation ◽  
Mixed Function Oxidase System ◽  
Pyrene Hydroxylase ◽  
Cytochrome P 450

The levels of cytochrome P-450, cytochrome b5, aminopyrine N-demethylase, and benzo[a]pyrene hydroxylase were depressed in hepatic microsomes following treatment of mice with the interferon inducer poly rI.rC. The decrease in the hepatic mixed function oxidase system was accompanied by an increase in the incorporation of amino acids into total microsomal protein. Fractionation of solubilized microsomes using a Sephacryl S-200 gel filtration column demonstrated that the increase in amino acid incorporation tended to be associated with proteins with molecular weights under 67 000. The fractions which contained cytochrome P-450 were further separated using a DEAE cellulose column. The amount of labelled amino acids associated with the cytochrome P-450 fractions was uniformly depressed in preparations from poly rI.rC treated animals compared with saline-treated controls. These results suggest that poly rI.rC causes a depression in the rate of synthesis of the apoprotein of cytochrome P-450 while increasing the incorporation of amino acids into other hepatic proteins. The decrease in apocytochrome P-450 synthesis explains the marked loss of drug biotransformation which occurs following induction of interferon.

scholarly journals Immunochemical detection of different isoenzymes of cytochrome P-450 induced in chick hepatocyte cultures

1989 ◽  
Vol 258 (1) ◽  
pp. 237-245 ◽  
Author(s):  
P Sinclair ◽  
J Frezza ◽  
J Sinclair ◽  
W Bement ◽  
S Haugen ◽  
...  
Keyword(s):  
Chick Embryo ◽  
Rabbit Antiserum ◽  
Enzyme Assays ◽  
Chick Embryos ◽  
Chemical Inducers ◽  
Hepatic Microsomes ◽  
Immunochemical Detection ◽  
Demethylase Activity ◽  
Cytochrome P 450

This study investigated whether the same cytochrome P-450 (P-450) isoenzymes were inducible in cultures of chick-embryo hepatocytes as in the liver of chicken embryos. We purified two isoenzymes of cytochrome P-450 from the livers of 17-day-old-chick embryos: one of molecular mass approx. 50 kDa induced in vivo by the phenobarbital-like inducer glutethimide, and the second of approx. 57 kDa induced by 3-methylcholanthrene. Rabbit antiserum against the 50 kDa protein inhibited benzphetamine demethylase activity in hepatic microsomes (microsomal fractions) from glutethimide-treated chick embryo. Antiserum to the 57 kDa protein inhibited ethoxyresorufin de-ethylase activity in hepatic microsomes from methylcholanthrene-treated chick embryo. Cultured chick hepatocytes were treated with chemicals known to induce isoenzymes of P-450 in rodent liver. The induced P-450s were quantified spectrophotometrically and characterized by immunoblotting and enzyme assays. From these studies, chemical inducers were classified into three groups: (i) chemicals that induced a P-450 isoenzyme of 50 kDa and increased benzphetamine demethylase activity: glutethimide, phenobarbital, metyrapone, mephenytoin, ethanol, isopentanol, isobutanol, lindane, lysodren; (ii) chemicals that induced a P-450 isoenzyme of 57 kDa and increased ethoxyresorufin de-ethylase activity: 3-methylcholanthrene and 3,3',4,4'-tetrachlorobiphenyl; and (iii) the mono-alpha-substituted 2,3',4,4',5-pentabromobiphenyl, which induced both proteins and both activities. The immunochemical data showed that chick-embryo hepatocytes in culture retain the inducibility of glutethimide- and methylcholanthrene-induced isoenzymes of P-450 that are inducible in the liver of the chicken embryo.

Hepatic drug metabolism is increased in poorly controlled insulin-dependent diabetes mellitus

1990 ◽  
Vol 123 (5) ◽  
pp. 550-556 ◽  
Author(s):  
Steven Goldstein ◽  
Anna Simpson ◽  
Paul Saenger
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Control ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Hepatic Drug Metabolism ◽  
Hepatic Drug ◽  
Insulin Dependent ◽  
Cytochrome P 450

Abstract. In addition to increased glycosylation of hemoglobin, abnormalities of other heme proteins such as cytochrome P-450 might also occur in patients with insulin-dependent diabetes mellitus. Antipyrine is a useful marker drug for cytochrome P-450 dependent hepatic drug metabolism. Antipyrine kinetics and urinary excretion of antipyrine metabolites were measured in 14 patients with insulin-dependent diabetes mellitus in poor metabolic control. Improvement in diabetic control in 9 patients, as measured by more normal HbA1 values, led to normalization of plasma antipyrine half-time (t½) and metabolism: the mean antipyrine t½ slowed from 4.7±0.2 (sem) initially to 7.8±0.3 h in these 9 patients and was thus nearly identical to that of normal subjects 8.6±1.0. Antipyrine plasma clearance improved in the 9 diabetic patients whose diabetic control improved. The apparent volume of distribution was normal on both occasions in the diabetic patients. These findings provide a new argument for tight metabolic control in patients with insulin-dependent diabetes mellitus.

Sign in / Sign up

Export Citation Format

Share Document