Interaction of aflatoxin B1 with the rat monooxygenase system and relationships to its acute toxic effect.
The effect of aflatoxin B1 (AFB1) on the liver microsomal and nuclear mixed function oxidase system (MFO) of adult male rats was studied at oral doses of 1 and 3 mg/kg. At first both doses increased the activities and concentrations of all P450 components followed. The maximum values were observed between 24 and 48 h and were dose- and enzyme-dependent. After 72 h the values dropped to 15-55% of the initial values. Inhibition of the MFO system lasted even after 120 h, when a trend to return to the normal values was already noticeable. We assume that AFB1 acts as an inductor of the monooxygenase system and the reactive electrophilic intermediate(s) bind irreversibly to or autocatalytically inactivate P450.
Hubálek
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Laboratory of Developmental Toxicology, Czechoslovak Academy of Sciences, Olesnice v Orlických horách.
D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D065607:Cytochrome P-450 Enzyme Inhibitors; D015786:Cytochromes b5 / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009249:NADP / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D065607:Cytochrome P-450 Enzyme Inhibitors; D009249:NADP; D015786:Cytochromes b5; D016604:Aflatoxin B1; D006899:Mixed Function Oxygenases