Abstract：
:Pyrrolizidine alkaloids (PAs) are known hepatotoxins. The execution of the toxicities of the alkaloids requires metabolic activation. Protein modification by reactive metabolites of PAs has been suggested to be an important mechanism of the toxic actions of PAs. The objectives of the present study were to define the interactions of dehydromonocrotaline (DHM) with lysine, lysine derivatives, a model peptide, and bovine serum albumin and to explore the lysine modification of hepatic proteins of animals given monocrotaline. DHM was found to react with the ε-amino group of all model compounds tested after incubation with DHM, and the modification reaction preferentially occurred at C7 of the necine base. The lysine residue modification with the same regioselectivity was also observed in hepatic proteins of mice treated with monocrotaline. The observed modification increased with the increase in doses administered to the animals. This work allowed us to better understand the mechanisms of the hepatotoxicity of monocrotaline.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Li W,Wang K,Lin G,Peng Y,Zheng Jdoi
10.1021/acs.chemrestox.5b00488subject
Has Abstractpub_date
2016-03-21 00:00:00pages
333-41issue
3eissn
0893-228Xissn
1520-5010journal_volume
29pub_type
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