title: 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.
abstract: 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.
authors.affiliation: Department of Life Sciences & Biotechnology, Jadavpur University, 188, Kolkata 700 032, India.
authors.forename: Semantee
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Srabasti
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Manna
authors.forename: Joydeep
authors.initials: J
authors.lastname: Das
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Ghosh
authors.forename: Ratan
authors.initials: R
authors.lastname: Gachhui
authors.forename: Parames C
authors.initials: PC
authors.lastname: Sil
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005937:Glucaric Acid; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007783:Lactones / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D000975:Antioxidants; C571832:D-Glucaric acid, 1,4-lactone; D007783:Lactones; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D005937:Glucaric Acid