Effects of ochratoxin A on the rat immune system after perinatal exposure.
Effects on the immune system after perinatal exposure to ochratoxin A (OA) were studied in Sprague-Dawley rats after single or repeated exposure of the dams. In a short-term study, dams with litters were given a single dose of OA (0, 10, 50 or 250 micrograms/kg body weight) on day 11 of lactation. The effects on cell numbers in spleen and thymus añd on the mitogen responses of lymphocytes were evaluated in the suckling pups on day 14 of lactation. The proliferative response of splenocytes to the T-cell mitogen Concanavalin A (Con A) was significantly stimulated in pups from dams given 10 or 50 micrograms OA/kg body weight as compared to control pups. In addition, proliferation of thymocytes in response to Con A was stimulated in pups from dams exposed to 50 micrograms OA/kg body weight. In a long-term, cross-fostering study comparing pre- and postnatal exposure, half of the dams received 50 micrograms OA/kg body weight 5 days a week by gastric intubation 2 weeks before mating, during gestation and then 7 days a week until weaning. Effects on immune parameters were studied in the pups on day 14 of lactation and at 13 weeks of age. Suppressed mitogenic responses were seen to both lipopolysaccharide (LPS) and Con A in prenatally exposed pups sampled on day 14 of lactation. At 13 weeks the response of splenocytes to LPS was still impaired. The primary antibody response to a viral antigen was also lower in the prenatally exposed pups than in the control pups. These effects on the immune response were not seen in the groups of pups exposed postnatally or both pre- and postnatally, although blood concentrations of OA were higher in these groups at the time of the first sampling. This indicates that the decrease in proliferation and antibody production resulted from prenatal modulation of the immune system. The results show that prenatal exposure to relatively low doses of OA may induce immunosuppression. In contrast, short-term exposure of suckling pups to OA via the milk stimulates the proliferative responses of lymphocytes to polyclonal activation.
Thuvander
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Toxicology Division, Swedish National Food Administration, Uppsala, Sweden.
Funseth
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Breitholtz-Emanuelsson
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Hallén
I P
IP
Oskarsson
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D000818:Animals; D000833:Animals, Suckling; D000917:Antibody Formation / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D007107:Immune System / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009183:Mycotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D008070:Lipopolysaccharides; D009183:Mycotoxins; D009793:Ochratoxins; D003208:Concanavalin A; C025589:ochratoxin A