Abstract:
:2,4-Dichlorophenol (2,4-DCP), an environmental pollutant, was reported to cause hepatotoxicity. The biochemical mechanisms of 2,4-DCP induced liver injury remain unknown. The present study showed that 2,4-DCP is chemically reactive and spontaneously reacts with GSH and bovine serum albumin to form GSH conjugates and BSA adducts. The observed conjugation/adduction apparently involved the addition of GSH and departure of chloride via the ipso substitution pathway. Two biliary GSH conjugates and one urinary N-acetyl cysteine conjugate were observed in rats given 2,4-DCP. The N-acetyl cysteine conjugate was chemically synthesized and characterized by mass spectrometry and NMR. As expected, 2,4-DCP was found to modify hepatic protein at cysteine residues in vivo by the same chemistry. The observed protein adduction reached its peak at 15 min and revealed dose dependency. The new findings allowed us to better understand the mechanisms of the toxic action of 2,4-DCP.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Li Q,Li W,Zhao J,Guo X,Zou Q,Yang Z,Tian R,Peng Y,Zheng Jdoi
10.1021/acs.chemrestox.0c00118subject
Has Abstractpub_date
2020-09-21 00:00:00pages
2351-2360issue
9eissn
0893-228Xissn
1520-5010journal_volume
33pub_type
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