Effect of various doses of deoxynivalenol on liver xenobiotic metabolizing enzymes in mice.
DON is one of the major mycotoxic contaminant of cereal grains throughout the world. The purpose of this investigation was to characterize the effects of a range of environmentally relevant doses of DON in mice exposed through a subchronic toxicological assay. Animals received 3 days per week for 4 weeks, 0.014, 0.071, 0.355 or 1.774 mg of toxin/kg b.w. All doses, except 0.014 mg/kg, provoked increases in plasma immunoglobulin A whereas there was no change in plasma biochemical parameters such as alkaline phosphatase, electrolytes or other immunoglobulins. Administration of 0.071 or 0.355 mg/kg doses led to increased liver microsomal pentoxyresorufin depentylase and cytosolic glutathione transferase activities. Examining protein modulation, western blot analyses liver fractions from mice receiving these doses revealed increased levels in both P450 2b, GST alpha and pi isoenzymes without any change in P450 1a expression. A significant competitive inhibition of deoxynivalenol on CDNB conjugation in vitro suggests that the mycotoxin is a putative substrate for glutathione S-transferases. These changes in liver xenobiotic metabolizing enzymes are discussed by considering the structural nature of deoxynivalenol and previous reports on similar effects exerted by other trichothecenes. These results suggest that a subchronic exposure to low doses of deoxynivalenol causes changes in the normal liver metabolism of xenobiotics.
Gouze
M E
ME
Department of Pharmacologie, Laboratoire de Pharmacologie-Toxicologie INRA, 180 Chemin de Tournefeuille, 31931 Toulouse, France.
Laffitte
J
J
Rouimi
P
P
Loiseau
N
N
Oswald
I P
IP
Galtier
P
P
D000284:Administration, Oral; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D002523:Edible Grain / Q000382:microbiology; D005506:Food Contamination; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*; D015262:Xenobiotics / Q000008:administration & dosage / Q000633:toxicity*
D007070:Immunoglobulin A; D014255:Trichothecenes; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; C007262:deoxynivalenol