Effects of phenobarbital and beta-naphthoflavone on the in vivo toxicity and in vitro metabolism of aflatoxin in an aflatoxin-resistant and control line of chickens.
The in vivo toxicity of aflatoxin and the in vitro microsomal metabolism of aflatoxin B1 (AFB1) were investigated in a population of chickens previously selected for resistance to aflatoxin (AR line) and a corresponding control population (NS line) after in vivo pretreatment with saline, sodium phenobarbital (PB), or beta-naphthoflavone (BNF) solutions. PB pretreatment increased survival and BNF pretreatment increased mortality in both the NS and AR lines when a single oral dose of aflatoxin was administered. The rate of in vitro metabolism of AFB1 was greater with microsomes from saline pretreated AR chicks than with microsomes from similarly treated NS chicks. In vivo pretreatment with PB increased AFB1 metabolism by NS and AR microsomes. After BNF pretreatment of vivo, AR microsomes metabolized more AFB1 than NS microsomes, and there was a dramatic decrease in AFB1 metabolism in NS microsomes. AFB1-dihydrodiol was the major metabolite produced by both lines, with aflatoxin M1 and aflatoxin Q1 recovered in small quantities from BNF-pretreated AR microsomal incubations only. These data indicate that increased in vivo resistance of the AR line to acute aflatoxicosis may be related to increased hepatic AFB1 metabolism and that genetic selection has resulted in altered in vitro quantitative and qualitative metabolism of AFB1 in the AR line.
Manning
R O
RO
Department of Pharmacology and Toxicology, University of Georgia, Athens.
Wyatt
R D
RD
Marks
H L
HL
D000348:Aflatoxins / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D004351:Drug Resistance; D005260:Female; D014453:Glucuronosyltransferase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D015651:Mycotoxicosis / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology*; D019324:beta-Naphthoflavone
D000348:Aflatoxins; D001571:Benzoflavones; D019324:beta-Naphthoflavone; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D010634:Phenobarbital