scholarly journals Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat

1975 ◽  
Vol 148 (2) ◽  
pp. 269-277 ◽  
Author(s):  
G Powis
Keyword(s):  
Cytochrome C ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Type I ◽  
Spectral Change ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Cytochrome P 450 ◽  
Aminopyrine Demethylation ◽  
Nadph Cytochrome C Reductase

Methanol and ethanol administered to rats as a single oral dose increased aniline hydroxylation by the hepatic microsomal fraction by a maximum of 169 and 66% respectively, whereas aminopyrine demethylation was inhibited by 51 and 61%. The concentration of microsomal cytochrome P-450, and the activities of NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were unchanged. Propan-2-ol, administered as a single oral dose, increased microsomal aniline hydroxylation by 165% and increased aminopyrine demethylation by 83%. The concentration of cytochrome P-450 was unchanged whereas NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were both increased by 38%. Methanol, ethanol and propan-2-ol administration resulted in a decreased type I spectral change but had no effect on the reverse type I spectral change. Methanol administration decreased the type II spectral change whereas ethanol and propan-2-ol had no effect. Cycloheximide blocked the increases in aniline hydroxylation and aminopyrine demethylation but could not completely prevent the decreases in aminopyrine demethylation. The increases in aniline hydroxylation were due to an increase in V, but Km was unchanged. The ability of acetone to enhance and compound SKF 525A to inhibit microsomal aniline hydroxylation was decreased by the administration of all three alcohols. The decrease in the metabolism of aminopyrine may result from a decrease in the binding to the type I site with a consequent failure of aminopyrine to stimulate the reduction of cytochrome P-450. Methanol administration may lead to an increase in aniline hydroxylation because of a failure of aniline to inhibit cytochrome P-450 reduction.

Temperature Influence on Basal Activity and Induction of Mixed Function Oxygenase Activity in Fundulus heteroclitus

1979 ◽  
Vol 36 (11) ◽  
pp. 1400-1405 ◽  
Author(s):  
John J. Stegeman
Keyword(s):  
Cytochrome C ◽  
Fundulus Heteroclitus ◽  
Reductase Activity ◽  
Control Fish ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Pyrene Hydroxylase ◽  
Mixed Function Oxygenase ◽  
Cytochrome P 450 ◽  
Nadph Cytochrome C Reductase

Treatment of Fundulus heteroclitus acclimated to 6.5 °C with benzo(a)pyrene did not elicit any change in the levels of hepatic microsomal NADH- or NADPH-cytochrome c reductase activity, nor in the levels of cytochrome P-450 or its catalytic activities. However, the same treatment offish at 16 5 °C resulted in a marked induction of benzo(a)pyrene hydroxylase and NADPH-cytochrome c reductase. Cytochrome P-450 content was also higher in the warm, treated fish and the Soret maximum of reduced, CO-treated microsomes was shifted to the violet. Levels of aminopyrine demethylase and NADH-cytochrome c reductase activities did not show a significant treatment effect. At neither temperature could treated and control fish be distinguished on the basis of in vitro inhibition of benzo(a)pyrene hydroxylase activity by 7,8-benzoflavone. Levels of NADPH-cytochrome c reductase and benzo(a)pyrene hydroxylase activities were greater in control Fundulus acclimated to 6.5 °C than to 16.5 °C, when normalized to microsomal protein, but not when based on body weight. The results indicate that habitat temperature alone may not affect the capacity for initial hydrocarbon metabolism in fish, but that it can strongly influence the induction of cytochrome P-450. Key words: temperature, cytochrome P-450, hydrocarbon metabolism, mixed-function oxygenase, Fundulus heteroclitus

Release of ferrous iron from ferritin by liver microsomes: a possible role in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin

1984 ◽  
Vol 62 (12) ◽  
pp. 1293-1300 ◽  
Author(s):  
Bruce Rowley ◽  
George D. Sweeney
Keyword(s):  
Cytochrome C ◽  
Flavin Mononucleotide ◽  
Monooxygenase System ◽  
Iron Release ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Ferritin Iron ◽  
Tetrachlorodibenzo P Dioxin ◽  
Cytochrome P 450 ◽  
Nadph Cytochrome C Reductase

Nonheme iron is synergistic with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing hepatotoxicity in mice. Fe2+ rather than Fe3+ is the probable toxin and we speculated that TCDD, an inducer of microsomal electron transport, might favour reduction of iron. We have defined a system which will release Fe2+ from ferritin (Fe3+) under anaerobic conditions and in the presence of added flavin mononucleotide (FMN). The rate of reduction of ferritin iron was proportional (a) to microsomal protein from 0.5 to >3 mg/mL, (b) to the activity of NADPH–cytochrome c reductase over 0.1 U/mL, (c) to ferritin at concentrations exceeding iron concentrations >200 μmol/L, and (d) to the concentration of FMN when it was less than 125 μmol/L. The system was approximately twice as active with NADPH as with NADH as electron donor. The linear phase of iron release did not commence immediately, but followed a delay (±0.5 min) after adding FMN to an anaerobic mixture containing microsomes, ferritin, an NADPH-generating system, and an oxygen-scavenging system. When microsomes from untreated, Phenobarbitaltreated (3 days), or TCDD-treated (1 or 3 weeks) rats were compared, iron release correlated most closely with the cytochrome P-450 concentration. However, when the microsomal proteins were solubilized and the NADPH–cytochrome c reductase and cytochrome P-450 activities were separated, reduction of ferritin iron was shown to be a function only of the reductase fraction, except that the delay in initiating release of Fe2+ was increased with purified reductase and decreased when a monooxygenase system was reconstituted with cytochrome (phenobarbital or TCDD induced) and lipid. These studies have defined a potentially important hepatic microsomal system able to release Fe2+ from ferritin iron, but have failed to indicate any feature unique to the dioxin-induced monooxygenase system.

Induction of cytochrome P-450, cytochrome b-5, nadph-cytochrome c reductase and change of cytochrome P-450 isozymes with long-term trichloroethylene treatment

Toxicology ◽  
1988 ◽  
Vol 53 (2-3) ◽  
pp. 239-249 ◽  
Author(s):  
Toshihiro Kawamoto ◽  
Tatsya Hobara ◽  
Kazuyuki Nakamura ◽  
Akihisa Imamura ◽  
Keiki Ogino ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome B ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Cytochrome P 450 ◽  
Nadph Cytochrome C Reductase
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