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United States Department of Agriculture

Agricultural Research Service

Title: The Effects of Vaccination on Riddelliine Toxicity in Rats

Authors
item Stegelmeier, Bryan
item Lee, Stephen
item James, Lynn
item Gardner, Dale
item Panter, Kip
item Ralphs, Michael
item Pfister, James

Submitted to: Poisonous Plant Global Research and Solutions
Publication Type: Book / Chapter
Publication Acceptance Date: May 31, 2006
Publication Date: June 20, 2007
Citation: Stegelmeier, B.L., Lee, S.T., James, L.F., Gardner, D.R., Panter, K.E., Ralphs, M.H., Pfister, J.A. 2007. The effects of vaccination on riddelliine toxicity in rats. Poisonous Plant Global Research and Solutions, Chpt. 15, pp. 89 - 93.

Interpretive Summary: Pyrrolizidine alkaloids (PAs) are plant toxins that commonly poison animals and humans. We have developed new detection systems using riddelliine (an unsaturated PA) that is connected to a large protein (PA conjugates). These conjugates are large enough that an animal’s immune system will make antibodies that specifically bind the free PA and possibly make them less toxic (like a vaccine). The purpose of this research is to test was to test if animals immunized with riddelliine-protein conjugates develop tolerance or resistance to riddelliine poisoning. Three groups of 30 weanling male rats were injected with two riddelliine conjugates or a sham ovalbumin conjugate. After 2 boosters injections the rats were divided into 3 groups of 10 rats. These groups were challenged by dosing by mouth with 5 mg/kg (25% LD50), 15 mg/kg (75% LD50) and 30 mg/kg (150% LD50) for 10 days. After dosing, the rats were euthanized; blood was collected; and tissues were collected, fixed and processed for histologic studies. Post mortem titers showed great variation in animal response to vaccination. Though there was little biochemical or histologic difference between the vaccination groups, the hepatic lesions appeared to be less severe in animals that had high titers. This suggests the immunization may alter riddelliine toxicity but additional studies are needed to verify this change.

Technical Abstract: Pyrrolizidine alkaloids (PAs) are plant toxins that poison livestock, wildlife and occasionally humans. We have developed several riddelliine (an unsaturated macrocyclic PA) conjugates for ELISA development. The purpose of this research is to test was to test if animals immunized with riddelliine-protein conjugates develop tolerance or resistance to riddelliine poisoning. Three groups of 30 weanling male rats were injected with two riddelliine conjugates or a sham ovalbumin conjugate. After a primary injection with complete Freund’s adjuvant, 2 boosters using incomplete Freund’s adjuvant were used. The immunized rats were divided into groups of 10 rats that were dosed via oral gavage with riddelline at doses of 5 mg/kg (25% LD50), 15 mg/kg (75% LD50) and 30 mg/kg (150% LD50) for 10 days. After dosing, the rats were euthanized; serum was collected; and tissues were collected, fixed and processed for histologic studies. Post mortem titers showed great variation in animal response to vaccination. Though there was little biochemical or histologic difference between the vaccination groups, the hepatic lesions appeared to be less severe in animals that had high titers. This suggests the immunization may alter riddelliine toxicity but additional studies are needed to verify this change.

Last Modified: 11/24/2014
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