Selective impairment of drug-metabolizing enzymes in pig liver during subchronic dietary exposure to aflatoxin B1.
Consequences of subchronic exposure to aflatoxin B1 (AFB1) on liver monooxygenase and transferase enzymes were compared in control pigs and pigs given 385, 867 or 1,807 microg AFB1/kg of feed for 4 weeks. Animals exposed to the highest dose of toxin developed clinical signs of aflatoxicosis, like liver fibrosis, hepatic dysfunction and decreased weight gain. This group had significantly lower levels of liver cytochrome P450, ethoxyresorufin O-deethylase (EROD) activity, testosterone metabolism, P450 1A and P450 3A protein expression. By comparison, mild degenerative hepatic changes, no hepatic dysfunction but a similar pattern of liver P450 enzymes activity without changes in P450 3A expression were observed in pigs exposed to 867 microg AFB1/kg of feed. Benzphetamine and aminopyrine N-demethylase activities were increased in pigs exposed to 867 or 1,807microg AFB1/kg of feed. Pigs exposed to 385 microg AFB1/kg of feed had low levels of EROD activity and all other biotransformation and clinical parameters remained at control levels. Aniline hydroxylase activity, P450 2C protein expression, UDP-glucuronosyl and glutathione S-transferase activities were unaffected at all doses of AFB1. In conclusion, P450 1A and P450 3A appear to be specific targets of AFB1 even if pig did not display clinical sign of liver toxicosis.
Meissonnier
Guylaine M
GM
Laboratoire de Pharmacologie-Toxicologie UR66, INRA, F-31931 Toulouse Cedex 9, France.
Laffitte
Joelle
J
Loiseau
Nicolas
N
Benoit
Etienne
E
Raymond
Isabelle
I
Pinton
Philippe
P
Cossalter
Anne-Marie
AM
Bertin
Gérard
G
Oswald
Isabelle P
IP
Galtier
Pierre
P
D016604:Aflatoxin B1 / Q000633:toxicity*; D000821:Animal Feed; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005506:Food Contamination; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014166:Transferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D016604:Aflatoxin B1; D006899:Mixed Function Oxygenases; D014166:Transferases