Biosynthesis, Physiological Disposition, and Biochemical Effects of Nephrotoxic Glutathione and Cysteine S-Conjugates
Abstract
These studies established that the biosynthesis of S- (pentachlorobutadienyl)glutathione (PCBG) is catalyzed preferentially by hepatic microsomal gluathione S-transferases. PCBG is further metabolized to the diconjugate 1,4-bis(glutathion-S-yl)-1,2,3,4-tetrachlorobuta-1,3-diene by hepatic cytosolic transferases. Studies on the synthesis of PCBG in the isolated, perfused rat liver showed that PCBG is eliminated in the bile at toxicologically relevant doses. The cysteine analog of PCBG S- (pentachlorobutadienyl)-L-cysteine (PCBC) is a potent nephrotoxin that damages mitochondria. PCBC, which is activated by renal mitochondrial cysteine conjugate Beta-lyase, inhibits mitochondrial protein, DNA, and RNA synthesis and destroys mitochondrial DNA, although the role of the effects in the observed mutagenicity of PCBC is unclear. Finally, preliminary studies on the intestinal absorption of PCBG indicate that the intact glutathione S-conjugate is absorbed in vivo and is cultured CaCo cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 14, 1990
- Accession Number
- ADA221522
Entities
People
- M. W. Anders
Organizations
- University of Rochester Medical Center