scholarly journals Postnatal development and sublobular distribution of cytochrome P-450 in rat liver: a microphotometric study.

1993 ◽  
Vol 41 (3) ◽  
pp. 397-400 ◽  
Author(s):  
J Watanabe ◽  
Y Asaka ◽  
S Kanamura
Keyword(s):  
Postnatal Development ◽  
Rat Liver ◽  
Perinatal Period ◽  
Postnatal Growth ◽  
Male Rats ◽  
Heterogeneous Distribution ◽  
Liver Lobule ◽  
Subsequent Period ◽  
The Difference ◽  
Cytochrome P 450

To study the process of expression of cytochrome P-450 (P-450) in hepatocytes during development, we measured microphotometrically the P-450 content in periportal and perivenular hepatocytes of male rats during peri- and postnatal growth. From Day 19 of gestation to Day 5 after birth, P-450 content in both periportal and perivenular hepatocytes increased markedly (periportal 1046%; perivenular 819%). The content in periportal hepatocytes remained unchanged from 5 to 20 days of age, and increased slightly (24%) from 20 to 45 days of age. However, the content in perivenular hepatocytes increased progressively (105%) between 5 and 45 days of age. The difference in P-450 content became apparent between periportal and perivenular hepatocytes after 7 days of age. The content in periportal or perivenular hepatocytes reached the adult level at 45 days of age. Therefore, the perinatal period is the time at which a marked increase in P-450 occurs in hepatocytes throughout the liver lobule. The subsequent period before weaning is the time at which the sublobular heterogeneous distribution of P-450 appears. The period after weaning is the time at which a slight increase in P-450 content in periportal hepatocytes and a marked increase in the enzyme in perivenular hepatocytes takes place.

INDEDUCIBILITY OF RAT LIVER CYTOCHROME P 450 DURING THE PERINATAL PERIOD

Abstracts ◽  
1978 ◽  
pp. 289
Author(s):  
Thierry CRESTEIL ◽  
Philippe BEAUNE ◽  
Jean-Paul LEROUX
Keyword(s):  
Rat Liver ◽  
Perinatal Period ◽  
Liver Cytochrome ◽  
Cytochrome P 450

scholarly journals Changes in certain kinetic properties of hepatic microsomal aniline hydroxylase and ethylmorphine demethylase associated with postnatal development and maturation in male rats

1969 ◽  
Vol 113 (4) ◽  
pp. 681-685 ◽  
Author(s):  
Theodore E. Gram ◽  
Anthony M. Guarino ◽  
David H. Schroeder ◽  
James R. Gillette
Keyword(s):  
Enzyme Activity ◽  
Postnatal Development ◽  
Male Rats ◽  
Kinetic Properties ◽  
Michaelis Constant ◽  
Microsomal Cytochrome ◽  
Aniline Hydroxylase ◽  
Mixed Function Oxidases ◽  
Demethylase Activity ◽  
Cytochrome P 450

1. Changes in certain kinetic properties (Vmax. and apparent Km) of hepatic microsomal mixed-function oxidases have been studied as a function of postnatal development and maturation in male rats. 2. Microsomal cytochrome P-450 content changed only slightly between 1 and 12 weeks of age. 3. Aniline hydroxylase activity (Vmax.) increased abruptly between 1 and 2 weeks of age to greater than adult activities and then returned to a plateau value between 4½ and 12 weeks of age. Ethylmorphine demethylase activity remained low and relatively constant between 1 and 3 weeks of age and then increased markedly (∼100%) between 3 and 4½ weeks. 4. The apparent Michaelis constant (Km) for aniline hydroxylation increased almost linearly with time between 1 and 6 weeks of age and tended to reach a plateau value thereafter. The apparent Km for ethylmorphine demethylation increased between 1 and 3 weeks of age and then decreased abruptly to a constant value between 6 and 12 weeks. 5. The data indicate that developmental changes in the activity of these microsomal oxidases do not correlate temporally with each other or with changes in microsomal cytochrome P-450 content. 6. The most dramatic changes in enzyme activity were associated with early development (1–3 weeks) and weaning (3–4 weeks). 7. Changes in weight of seminal vesicle, a criterion of sexual maturation in male rats, were most prominent between 6 and 8 weeks of age and thus appeared to be separated in time from the prominent changes in enzyme activity.

Inactivation of rat liver microsomal steroid hydroxylations by 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine: evidence for selectivity among steroid-inducible cytochrome P450IIIA forms

1990 ◽  
Vol 68 (12) ◽  
pp. 1533-1541 ◽  
Author(s):  
D. S. Riddick ◽  
I. McGilvray ◽  
G. S. Marks
Keyword(s):  
Rat Liver ◽  
Time Dependent ◽  
Female Rats ◽  
Male Rats ◽  
Prosthetic Group ◽  
Treated Male ◽  
Hepatic Microsomes ◽  
Dependent Inactivation ◽  
Heme Prosthetic Group ◽  
Cytochrome P 450

Various 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) cause mechanism-based inactivation of cytochrome P-450 (P-450) via destruction of the heme prosthetic group. This is an important component of these compounds' porphyrinogenic mechanism. In an attempt to map the P-450 isozyme selectivities of DDC analogues, we have examined the effects of these compounds on the regioselective and stereoselective hydroxylation of androstenedione (AD) and progesterone (PG) in rat liver microsomal systems. In microsomes from phenobarbital-treated male rats, DDC analogues did not cause time-dependent inactivation of AD 7α-hydroxylase, AD 16β-hydroxylase, and PG 21-hydroxylase, selective markers for P450IIA1/2, IIB1, and IIC6, respectively. In contrast, DDC analogues were effective inactivators of PG 2α-hydroxylase and steroid 6β-hydroxylases, selective markers for P450IIC11 and IIIA forms, respectively. We conclude that differences in porphyrinogenicity observed with various DDC analogues are not likely to be due to the selective destruction of different P-450 isozymes by different analogues, but rather to properties of the DDC analogues themselves. 4-Ethyl DDC was found to be capable of discriminating between P450IIIA subfamily forms. In microsomes from untreated male rats, which express P450IIIA2 but not IIIA1, 4-ethyl DDC inactivated both AD and PG 6β-hydroxylases. However, in microsomes from dexamethasone-treated female rats, which express P450IIIA1 but not IIIA2, no inactivation of the steroid 6β-hydroxylases was observed. Thus, 4-ethyl DDC appears to be a potentially valuable tool for differentiating between P450IIIA forms.Key words: 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine, cytochrome P-450, mechanism-based inactivation, rat hepatic microsomes, steroid hydroxylations.

scholarly journals The distribution of glutathione in the rat liver lobule

1979 ◽  
Vol 182 (1) ◽  
pp. 103-108 ◽  
Author(s):  
M T Smith ◽  
N Loveridge ◽  
E D Wills ◽  
J Chayen
Keyword(s):  
Rat Liver ◽  
Reduced Glutathione ◽  
Central Vein ◽  
Electrophilic Attack ◽  
Liver Lobule ◽  
Microsomal Cytochrome ◽  
Cytochemical Method ◽  
Toxic Metabolites ◽  
Cytochrome P 450

A quantitative cytochemical method was developed for measuring the GSH (reduced glutathione) content of hepatocytes in different regions of the rat liver lobule. Use of this method enabled us to show that GSH is not evenly distributed within the rat liver lobule. The hepatocytes located within 100 micrometer of the central vein contain much less GSH than do those in other regions of the rat liver lobule. We suggest that this partially explains the peculiar susceptibility of these cells to electrophilic attack by toxic metabolites formed via the microsomal cytochrome P-450 system.

scholarly journals Growth hormone and drug metabolism. Acute effects on microsomal mixed-function oxidase activities in rat liver

1976 ◽  
Vol 154 (2) ◽  
pp. 433-438 ◽  
Author(s):  
J T. Wilson ◽  
T C. Spelsberg
Keyword(s):  
Growth Hormone ◽  
Drug Metabolism ◽  
Rat Liver ◽  
Oxidase Activity ◽  
Male Rats ◽  
Mixed Function Oxidase ◽  
Liver Growth ◽  
Mixed Function Oxidases ◽  
Cytochrome P 450 ◽  
Mixed Function Oxidase Activity

Adult male rats were subjected either to sham operation or to hypophysectomy and adrenalectomy and maintained for a total of 10 days before treatment with growth hormone. Results of the early effects of growth hormone on the activities of the mixed-function oxidases in rat liver over a 96h period after growth-hormone treatment are presented. 2. Hypophysectomy and adrenalectomy result in decreased body and liver weight and decreased drug metabolism (mixed-function oxidases). Concentrations of electron-transport-system components are also decreased. 3. In the hypophysectomized/adrenalectomized rats, growth hormone decreases the activities of the liver mixed-function oxidases and the cytochrome P-450 and cytochrome c reductases, as well as decreasing the concentration of cytochrome P-450 compared with that of control rats. Similar but less dramatic results are obtained with sham-operated rats. 4. It is concluded that whereas growth hormone enhances liver growth, including induction of many enzyme activities, it results in a decrease in mixed-function oxidase activity. Apparently, mixed-function oxidase activity decreases in liver when growth (mitogenesis) increases.

Induction of Cytochrome P-450-linked Monooxygenase System in Rat Liver Microsomes by Xiao-Chaihu-Tang

1996 ◽  
Vol 24 (02) ◽  
pp. 143-151 ◽  
Author(s):  
Taira Ohnishi ◽  
Hirohito Yoneyama ◽  
Tatushichiro Hamamoto ◽  
Toshihiko Ishida ◽  
Jirou Takahara ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
The Other ◽  
Female Rats ◽  
Male Rats ◽  
Monooxygenase System ◽  
Rat Liver Microsomes ◽  
Female Rat ◽  
Metabolic Rates ◽  
Cytochrome P 450

The administration of Xiao-Chaihu- Tang (TJ-9) for 2 weeks induced a 25% increase in the content of cytochrome P-450 in female rat liver microsomes, while the content in male rats remained unchanged. The enzymatic activities toward various xenobiotics were stimulated in female rats, the levels being in the range of 125-250% of those in the control rats. Among these xenobiotics, the metabolic rates for substrates of cytochrome P-450 2El were significantly enhanced in female rats. On the other hand, the activities toward various xenobiotics in male rats were unchanged. When 3-methylcholanthrene was given to rats for a week, the augmentation of cytochrome P-450 content and the stimulation ofxenobiotic metabolism were observed. However, co-administration ofTJ-9 did not alter the effect of 3-methylcholanthrene described above.

Sign in / Sign up

Export Citation Format

Share Document