Effects of Non-Gonadal Hormones on Rat Liver Drug-Metabolizing Enzymes and Cytochrome P-450 during Early Postnatal Development

1979 ◽  
Vol 7 (5) ◽  
pp. 1103-1104
Author(s):  
JULIAN E. A. LEAKEY ◽  
JAMES R. FOUTS ◽  
GEOFFREY J. DUTTON
Keyword(s):  
Postnatal Development ◽  
Rat Liver ◽  
Gonadal Hormones ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Early Postnatal Development ◽  
Cytochrome P 450

scholarly journals The effects of chemical porphyrogens and drugs on the activity of rat liver tryptophan pyrrolase

1973 ◽  
Vol 136 (4) ◽  
pp. 885-892 ◽  
Author(s):  
Abdulla A.-B. Badawy ◽  
Myrddin Evans
Keyword(s):  
Mental Disorders ◽  
Rat Liver ◽  
Daily Injection ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Tryptophan Pyrrolase ◽  
Cytochrome P 450 ◽  
Subsequent Administration

1. Drugs such as phenobarbitone and phenylbutazone, which increase the concentration of microsomal haem and cytochrome P-450, also increase the saturation of rat liver apo-(tryptophan pyrrolase) with its haem activator, as does the haem precursor 5-aminolaevulinate. 2. At 4h after the administration of the porphyrogens 2-allyl-2-isopropylacetamide, 3,5-diethoxycarbonyl-1,4-dihydrocollidine and griseofulvin, the total pyrrolase activity is increased whereas the haem saturation of the apoenzyme is decreased. This decreased saturation is prevented by pretreatment of the animals with the inhibitor of drug-metabolizing enzymes, SKF 525-A. 3. Pretreatment of rats with the above porphyrogens inhibits the rise in holo-(tryptophan pyrrolase) activity produced by subsequent administration of cortisol, tryptophan and 5-aminolaevulinate with two single exceptions, the possible reasons for which are discussed. 4. At 24h after the administration, in starved rats, of a single daily injection of the above porphyrogens for 1 or 2 days, the holoenzyme activity is significantly increased. 5. It is suggested that the saturation of rat liver apo-(tryptophan pyrrolase) with its haem activator can be modified by treatment known to cause destruction, inhibition of synthesis, increased utilization and enhanced synthesis of liver haem. The possible involvement of the latter phenomenon in the aetiology of mental disorders in some patients with porphyria is discussed.

scholarly journals Effect of development on the activity of microsomal drug-metabolizing enzymes in rat liver

1971 ◽  
Vol 124 (1) ◽  
pp. 19-24 ◽  
Author(s):  
T. K. Basu ◽  
J. W. T. Dickerson ◽  
D. V. W. Parke
Keyword(s):  
Rat Liver ◽  
Drug Metabolizing Enzymes ◽  
Mixed Function Oxidase ◽  
Peak Activity ◽  
Stock Diet ◽  
Metabolizing Enzymes ◽  
Glucuronyl Transferase ◽  
Triton X ◽  
Cytochrome P 450 ◽  
Commercial Stock

1. The activity of rat liver microsomal drug-metabolizing enzymes was determined at various ages between 6 and 100 days post natum. The enzymes studied were: aromatic hydroxylases by using as substrate biphenyl, which is metabolized by oxidation to 2- and 4-hydroxybiphenyl; nitroreductase by using p-nitrobenzoate as substrate, which is metabolized by reduction to p-aminobenzoate; glucuronyl synthetase by using 4-methylumbelliferone as the substrate, which is conjugated to give 4-methylumbelliferone glucuronide, and cytochrome P-450, which is regarded as the major terminal mixed-function oxidase in hepatic microsomal hydroxylations. 2. The activity of biphenyl 2-hydroxylase reached a peak at 21 days, biphenyl 4-hydroxylase and 4-methyl glucuronyl transferase at 24 days, cytochrome P-450 at 31 days, and p-nitrobenzoate reductase at 38 days of age. After the peak activity had been reached, the activity of each enzyme decreased with age, and in the case of biphenyl 2-hydroxylase the activity fell to a negligible value at 52 days of age. 3. Neither the addition of Triton X-100 to the incubation medium nor the treatment of the animals with phenobarbital resulted in any increase in the activity of biphenyl 2-hydroxylase at 52 days of age. 4. The activity of biphenyl 2-hydroxylase was threefold higher in rats fed on a synthetic diet than in rats fed on a commercial stock diet. 5. These findings are discussed.

scholarly journals Loss of haem in rat liver caused by the porphyrogenic agent 2-allyl-2-isopropylacetamide

1971 ◽  
Vol 124 (4) ◽  
pp. 767-777 ◽  
Author(s):  
F. De Matteis
Keyword(s):  
Rat Liver ◽  
Microsomal Fraction ◽  
Direct Evidence ◽  
Gradual Increase ◽  
Rapid Loss ◽  
Metabolizing Enzymes ◽  
Liver Microsomal Fraction ◽  
Green Pigments ◽  
Cytochrome P 450 ◽  
Increased Activity

1. The effect of a single dose of 2-allyl-2-isopropylacetamide on the cytochrome P-450 concentration in rat liver microsomal fraction was studied. The drug caused a rapid loss of cytochrome P-450 followed by a gradual increase to above the normal concentration. 2. The loss of cytochrome P-450 was accompanied by a loss of microsomal haem and by a brown–green discoloration of the microsomal fraction suggesting that a change in the chemical constitution of the lost haem had taken place. Direct evidence for this was obtained by prelabelling the liver haems with radioactive 5-aminolaevulate: the drug caused a loss of radioactivity from the haem with an increase of radioactivity in a fraction containing certain un-identified green pigments. 3. Evidence was obtained by a dual-isotopic procedure that rapidly turning-over haem(s) may be preferentially affected. 4. The loss of cytochrome P-450 as well as the loss of microsomal haem and the discoloration of the microsomal fraction were more intense in animals pretreated with phenobarbitone and were much less evident when compound SKF 525-A (2-diethylaminoethyl 3,3-diphenylpropylacetate) was given before 2-allyl-2-isopropylacetamide, suggesting that the activity of the drug-metabolizing enzymes may be involved in these effects. 5. The relevance of the destruction of liver haem to the increased activity of 5-aminolaevulate synthetase caused by 2-allyl-2-isopropylacetamide is discussed.

An unusual profile of musk xylene-induced drug-metabolizing enzymes in rat liver

1993 ◽  
Vol 45 (8) ◽  
pp. 1659-1665 ◽  
Author(s):  
Iwata Nobuhisa ◽  
Minegishi Ken-Ichiro ◽  
Suzuki Kazuhiro ◽  
Ohno Yasuo ◽  
Igarashi Takashi ◽  
...  
Keyword(s):  
Rat Liver ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Musk Xylene
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