Immunotoxicity of the pyrrolizidine alkaloid monocrotaline following subchronic administration to C57Bl/6 mice.
Monocrotaline (MCT) is a member of a class of compounds known as pyrrolizidine alkaloids (PAs). PAs are found in the leaves and seeds of a variety of plant species. The potential intoxication of livestock and man through the ingestion of contaminated grains and other foods makes PAs a significant toxicological concern. MCT exposure in rats results in lesions to hepatic and cardiopulmonary tissues as well as alterations in lymphoid organ cellularity. However, no previous studies have investigated MCT-induced functional alterations in the immune system. In the present study, MCT was administered by gavage for 14 days at 0, 10, 25, 50, 75, and 150 mg/kg to female C57Bl/6 mice. The antibody-mediated immune response to sheep red blood cells (SRBC) was assessed using the plaque-forming cell (PFC) assay and the hemolytic antibody isotope release assay (HAIR). Additionally, the cytotoxic T-lymphocyte (CTL) response to allogeneic P815 tumor cells was determined after MCT exposure. Although hepatic and pulmonary lesions are common sequelae to MCT exposure in rats, the C57Bl/6 mouse appeared to be more resistant to these effects on the basis of histopathological examination. Furthermore, the overt toxicity of MCT was minimal with respect to organ weight changes in liver, kidney, and lung. In contrast, a dose-dependent suppression in the antibody response to SRBC was observed with a minimum significant dose of 25 mg/kg. At this dose the number of anti-SRBC PFC per 10(6) spleen cells and the amount of anti-SRBC antibody measured in the HAIR assay were 57 and 59% of control, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Deyo
J A
JA
College of Veterinary Medicine, Oregon State University, Corvallis 97331-4802.
Kerkvliet
N I
NI
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007114:Immunization; D007121:Immunocompetence / Q000187:drug effects*; D007958:Leukocyte Count / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology; D008168:Lung / Q000033:anatomy & histology; D051379:Mice; D008815:Mice, Inbred Strains; D016686:Monocrotaline; D009929:Organ Size / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D011897:Random Allocation; D013154:Spleen / Q000276:immunology; D010948:Viral Plaque Assay
D000906:Antibodies; D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline