Graduate Thesis Or Dissertation

 

Immunotoxicity of the pyrrolizidine alkaloid monocrotaline in C57B1/6 mice Public Deposited

Downloadable Content

Download PDF
https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/qb98mj87q

Descriptions

Attribute NameValues
Creator
Abstract
  • Monocrotaline (MCT) is a member of a class of naturally occurring phytotoxins known as pyrrolizidine alkaloids (PAs). Exposure to PAs can result in liver and cardiopulmonary lesions as well as lymphoid organ atrophy. In the present study C57BI/6 (B6) mice received MCT (0-150 mg/kg/day, po) for 14 days. Overt toxicity was minimal and observed only at highly immunosuppressive doses. Following MCT exposure, significant dose-dependent suppressions were observed in the following immune responses: numbers of antibody producing cells, cytotoxic T- lymphocyte activity, and NK cell cytotoxicity. The antibody responses to the T cell-dependent antigen, SRBC, and the T cell-independent (TI) antigens, DNP-Ficoll and TNP-LPS, were decreased with identical dose response curves. This, along with data showing MCT decreased blastogenesis of B cells more than T cells at the lowest dose level, and that high doses induced significant decreases in the total number of B cells only, suggest that the B cell may be more sensitive than T cells, NK cells , or macrophages. The liver and lung toxicity of MCT is believed to be mediated through its metabolism by mixed function oxidase (MFO) enzymes to reactive pyrroles (monocrotaline pyrrole, MCTP; and dihydropyrrolizine, DHP). Accordingly, it was our hypothesis that the immunotoxicity could be modulated by altering MFO activity. To test this, mice were given a single dose of MCT (100 or 200 mg/kg, po) after MFO induction with phenobarbital; in other experiments mice received the MFO inhibitor chloramphenicol immediately before and 3 hrs after a single exposure to MCT (300 mg/kg, po). However, neither MFO induction nor inhibition significantly altered the immunosuppressive potency of MCT. The antibody and blastogenic responses of splenic lymphocytes directly exposed to MCT (1-3 mM) or MCTP (1-8 μM) in culture were inhibited in a concentration-dependent manner, indicating that both parent and metabolite were immunotoxic. However, the inability to alter the in vivo immunotoxicity by altering MFO activity questions the role this metabolite may play in vivo. In conclusion, the immune system in B6 mice is a sensitive target of MCT toxicity. Inhibition of blastogenesis appears to be one mechanism of MCT-induced immunosuppression. In contrast to other toxic effects of MCT, our results suggest that the parent compound itself plays a significant role in the immunotoxicity.
Resource Type
Date Available
Date Copyright
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Non-Academic Affiliation
Subject
Rights Statement
Peer Reviewed
Language
Digitization Specifications
  • File scanned at 300 ppi (Monochrome) using ScandAll PRO 1.8.1 on a Fi-6770A in PDF format. CVista PdfCompressor 5.0 was used for pdf compression and textual OCR.
Replaces
Additional Information
  • description.provenance : Submitted by Kaylee Patterson (kdpscanner@gmail.com) on 2013-01-18T21:18:06Z No. of bitstreams: 1 DeyoJamesA1992.pdf: 3646459 bytes, checksum: 1594fca15b50d8c001d97ed5a2d84c30 (MD5)
  • description.provenance : Made available in DSpace on 2013-02-12T18:08:13Z (GMT). No. of bitstreams: 1 DeyoJamesA1992.pdf: 3646459 bytes, checksum: 1594fca15b50d8c001d97ed5a2d84c30 (MD5) Previous issue date: 1991-10-29
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2013-01-18T21:44:05Z (GMT) No. of bitstreams: 1 DeyoJamesA1992.pdf: 3646459 bytes, checksum: 1594fca15b50d8c001d97ed5a2d84c30 (MD5)
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2013-02-12T18:08:13Z (GMT) No. of bitstreams: 1 DeyoJamesA1992.pdf: 3646459 bytes, checksum: 1594fca15b50d8c001d97ed5a2d84c30 (MD5)

Relationships

Parents:

This work has no parents.

Items