Subclinical doses of T-2 toxin impair acquired immune response and liver cytochrome P450 in pigs.
This study was designed to investigate the effect of subclinical doses of T-2 toxin on liver drug-metabolizing enzymes and the immune response. Pigs were offered over a 28-day period either a control diet or diets contaminated with 540, 1324 or 2102microg pure T-2toxin/kg feed. Pigs were immunized with ovalbumin and subsequent humoral and cellular immune responses measured. Monooxygenase and transferase enzyme activities and protein expression were investigated in liver tissue samples. Pigs fed 1324 or 2102microg T-2toxin/kg feed exhibited reduced anti-ovalbumin antibody production without significant alteration to specific lymphocyte proliferation. The livers of pigs exposed to T-2 toxin presented normal cytochrome P450 content, UGT 1A and P450 2B, 2C or 3A protein expression, and glutathione- and UDP glucuronosyl-transferase activities. However, P450 1A related activities (ethoxyresorufin O-deethylation and benzo-(a)-pyrene hydroxylation) were reduced for all pigs given T-2 toxin, with P450 1A protein expression decreased in pigs fed the highest dose. In addition T-2 toxin exposure reduced certain N-demethylase activities. The results of this study confirm the immunotoxic properties of T-2 toxin, in particular toward the humoral immune response. The reduction of monooxygenase activities, even though the liver presented no tissue lesion or lipid peroxidation, suggests possible deleterious interactions of T-2 toxin with these enzymes.
Meissonnier
G M
GM
Laboratoire de Pharmacologie-Toxicologie UR66, INRA, F-31931 Toulouse, France.
Laffitte
J
J
Raymond
I
I
Benoit
E
E
Cossalter
A-M
AM
Pinton
P
P
Bertin
G
G
Oswald
I P
IP
Galtier
P
P
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007114:Immunization; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D013552:Swine; D013605:T-2 Toxin / Q000008:administration & dosage / Q000633:toxicity*
D010047:Ovalbumin; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D013605:T-2 Toxin