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
| Autor: | Semantee Bhattacharya, Srabasti Chatterjee, Jyotirmoy Ghosh, Prasenjit Manna, Ratan Gachhui, Joydeep Das, Parames C. Sil |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Programmed cell death Time Factors Antioxidant Cell Survival Health Toxicology and Mutagenesis medicine.medical_treatment Blotting Western Cell Culture Techniques Mitochondria Liver Oxidative phosphorylation Mitochondrion Biology Toxicology Biochemistry Antioxidants Protein Carbonylation Glucaric Acid Lactones Mice tert-Butylhydroperoxide medicine Animals Cytotoxicity Molecular Biology Cells Cultured Membrane Potential Mitochondrial Cell Death Dose-Response Relationship Drug Cytochrome c General Medicine Flow Cytometry Oxidative Stress Cytosol Hepatocytes biology.protein Molecular Medicine Lipid Peroxidation Reactive Oxygen Species Intracellular |
| Zdroj: | Journal of Biochemical and Molecular Toxicology. 25:341-354 |
| ISSN: | 1095-6670 |
| DOI: | 10.1002/jbt.20393 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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