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Prophylactic role of D ‐saccharic acid‐1,4‐lactone in tertiary butyl hydroperoxide induced cytotoxicity and cell death of murine hepatocytes via mitochondria‐dependent pathways
Author(s) -
Bhattacharya Semantee,
Chatterjee Srabasti,
Manna Prasenjit,
Das Joydeep,
Ghosh Jyotirmoy,
Gachhui Ratan,
Sil Parames C.
Publication year - 2011
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20393
Subject(s) - cytotoxicity , apoptosis , mitochondrion , programmed cell death , chemistry , cytosol , intracellular , viability assay , antioxidant , cytochrome c , cell , microbiology and biotechnology , biochemistry , oxidative stress , in vitro , biology , enzyme
D‐Saccharic acid 1,4‐lactone (DSL) is a derivative of D‐glucaric acid. It is a beta‐glucuronidase inhibitor and possesses anticarcinogenic, detoxifying, and antioxidant properties. In the present study, the protective effects of DSL were investigated against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death in vitro using murine hepatocytes. Exposure of TBHP caused a reduction in cell viability, enhanced the membrane leakage, and disturbed the intracellular antioxidant machineries in murine hepatocytes. Investigating the signaling mechanism of TBHP‐induced cellular pathophysiology and protective action of DSL, we found that TBHP exposure disrupted mitochondrial membrane potential, facilitated cytochrome c release in the cytosol, and led to apoptotic cell death via mitochondria‐dependent pathways. DSL counteracted these changes and maintained normalcy in hepatocytes. Combining, results suggest that DSL possesses the ability to ameliorate TBHP‐induced oxidative insult, cytotoxicity, and apoptotic cell death probably due to its antioxidant activity and functioning via mitochondria‐dependent pathways. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:341–354 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20393