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Development of an immunoassay approach for diagnosis of hepatotoxicity induced by pyrrolizidine alkaloids (PAs)

总结

Pyrrolizidine alkaloids (PAs) distributes widely in plants, including medicinal herbs, and also contaminate our daily-consumed foodstuffs, such as grain crops, honey and milk. Yearly, many intoxication cases induced by PAs are reported. However, up to date, no specific and sensitive method is available to diagnose the PA-induced toxicity. It is well known that PAs exert their toxicity by metabolic activation to form the electrophilic “pyrrolic” metabolites, which can rapidly react with macromolecules, such as protein to form pyrrole-protein adducts. Thus, such pyrrole-protein adducts had a potential to be developed as a biomarker of toxicity induced by PAs. In this invention, we describe a development of an immunoassay approach for the analysis of pyrrole-protein adducts, which can be utilized for the diagnosis and assessment of hepatotoxicity induced by PA-containing natural products and PA-contaminated foodstuffs.

Advantages and improvements over existing technology The present invention provides antibodies specifically recognising pyrrole-protein adducts, which are formed in the body after metabolic activation of toxic pyrrolizidine alkaloids. The developed antibodies successfully detect the pyrrole-protein adducts in biological samples of rats and mice treated with pure pyrrolizidine alkaloids or pyrrolizidine alkaloid-containing herbs, using Western blot, competitive ELISA assays and immunohistology. The developed antibodies have a potential to be used for the diagnosis and assessment of the hepatotoxicity induced by PAs and PA-containing natural products in clinic and research laboratories. The developed antibodies are novel.

附加资料

Inventor: Schaefer, Brian C. | Marrack, Philippa | Kappler, John W.
Priority Number: US7169570B2
IPC Current: C12Q000102 | G01N003350 | G01N003353 | G01N0033567 | G01N003358 | G01N003368
US Class: 43500721 | 43500724 | 435029 | 435377 | 436063 | 436086
Assignee Applicant: National Jewish Medical and Research Centernver
Title: Method to identify regulators of cellular activation using Bcl10
Usefulness: Method to identify regulators of cellular activation using Bcl10
Summary: The methods are useful for evaluating activation of Bcl10 in a cell in response to a putative stimulus (claimed).

主要类别

生物医学

细分类别

DNA /基因工程

申请号码

11/MED/453

其他

Inventor(s): Professor LIN Ge, School of Biomedical Sciences Licensing Status: Available

国家/地区

香港