Induction of cytochrome P-448 activity as exemplified by the O-deethylation of ethoxyresorufin

Iwasaki, Katsunori; Lum, Peck Y.; Ioannides, Costas; Parke, Dennis V.

doi:10.1016/0006-2952(86)90679-9

Cited by 40 publications

(4 citation statements)

References 25 publications

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“…As we have previously reported (Hashemi et al, 2000), ethoxyresorufin O-deethylase activity in rat slices declined on incubation, with very little activity being detectable after 48 h, and this was accompanied by a similar loss in CYP1A apoprotein levels. Exposure of the slices, however, to benzo[a]pyrene led to a marked, increase in activity, the highest rise occurring after a 24-h incubation, similar to observations made in vivo following treatment of rats with this compound (Iwasaki et al, 1986). A rise in this activity in rat slices has already been reported following incubation with other CYP1A1 inducers such as ␤-naphthoflavone (Müller et al, 1996), TCDD (Drahushuk et al, 1996) and Aroclor 1254 (Price et al, 2004).…”

Section: Discussionsupporting

confidence: 72%

Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities

et al. 2007

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Section: Discussionsupporting

confidence: 72%

Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities

et al. 2007

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“…The cytochrome P-4501A isozymes were detected in kidney but at levels markedly lower than those seen in liver of rats using monoclonal antibodies recognizing MC-induced cytochromes [41,42]. The lower activity of cytochrome P450 1A in kidney was induced after treatments of rats with either PAH, β-NF, or 2-AAF [43,44]. With TCDD as inducing agent, immuno quantification showed a marked increase in cytochrome P4501A1, which accounted for 30% of total rat kidney cytochrome P-450.…”

Section: Kidneymentioning

confidence: 99%

Drug-Metabolizing Enzymes Mechanisms and Functions

Sheweita

2000

CDM

213

128

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Drug-metabolizing enzymes are called mixed-function oxidase or monooxygenase and containing many enzymes including cytochrome P450, cytochrome b5, and NADPH-cytochrome P450 reductase and other components. The hepatic cytochrome P450s (Cyp) are a multigene family of enzymes that play a critical role in the metabolism of many drugs and xenobiotics with each cytochrome isozyme responding differently to exogenous chemicals in terms of its induction and inhibition. For example, Cyp 1A1 is particularly active towards polycyclic aromatic hydrocarbons (PAHs), activating them into reactive intermediates those covalently bind to DNA, a key event in the initiation of carcinogenesis. Likewise, Cyp 1A2 activates a variety of bladder carcinogens, such as aromatic amines and amides. Also, some forms of cytochrome P450 isozymes such as Cyp 3A and 2E1 activate the naturally occurring carcinogens (e.g. aflatoxin B1) and N-nitrosamines respectively into highly mutagenic and carcinogenic agents. The carcinogenic potency of PAHs, and other carcinogens and the extent of binding of their ultimate metabolites to DNA and proteins are correlated with the induction of cytochrome P450 isozymes. Phase II drug-metabolizing enzymes such as glutathione S-transferase, aryl sulfatase and UDP-glucuronyl transferase inactivate chemical carcinogens into less toxic or inactive metabolites. Many drugs change the rate of activation or detoxification of carcinogens by changing the activities of phases I and II drug-metabolizing enzymes. The balance of detoxification and activation reactions depends on the chemical structure of the agents, and is subjected to many variables that are a function of this structure, or genetic background, sex, endocrine status, age, diet, and the presence of other chemicals. It is important to realize that the enzymes involved in carcinogen metabolism are also involved in the metabolism of a variety of substrates, and thus the introduction of specific xenobiotics may change the operating level and the existence of other chemicals. The mechanisms of modification of drug-metabolizing enzyme activities and their role in the activation and detoxification of xenobiotics and carcinogens have been discussed in the text.

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“…Myristicin caused a 4-fold increase in EROD activity in rat liver, nearly half the increase seen for safrole. No increase in EROD activity in the lung or kidney was observed for either substance (Iwasaki et al, 1986). …”

Section: Enzyme Induction and Inhibitionmentioning

confidence: 99%

Joint FAO/WHO Expert Committee on Food Additives (JECFA)

Sagert¹

2008

Encyclopedia of Global Health

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Induction of cytochrome P-448 activity as exemplified by the O-deethylation of ethoxyresorufin

Cited by 40 publications

References 25 publications

Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities

Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities

Drug-Metabolizing Enzymes Mechanisms and Functions

Joint FAO/WHO Expert Committee on Food Additives (JECFA)

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