Immunotoxicity of the Pyrrolizidine Alkaloid Monocrotaline following Subchronic Administration to C57BI/6 Mice

Abstract

Immunotoxicity of the Pyrrolizidine Alkaloid Monocrotaline following Subchronic Administration to C57B1/6 Mice. DEYO, J. A., AND KHRKVUET, N. I. (1990). Fundam. Appl. Toxicol14, 842–849. 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 C57B1/6 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 allo-geneic P815 tumor cells was determined after MCT exposure. Although hepatic and pulmonary lesions are common sequelae to MCT exposure in rats, the C57B1/6 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 106 spleen cells and the amount of anti-SRBC antibody measured in the HAIR assay were 57 and 59% of control, respectively. The CTL response was significantly decreased (38% of control, 30: 1 E:T), and the total number of CTL lytic units per spleen was 12% of control at 75 mg/kg. Antibody titers to P815 were also dose-dependently suppressed. Therefore, we conclude that the immune system inC57Bl/6 mice is a sensitive target of MCT toxicity.