Involvement of mitochondria mediated pathways in hepatoprotection conferred by Fumaria parviflora Lam. extract against nimesulide induced apoptosis in vitro
| Autor: | Madhulika Tripathi, Poonam Kakkar, Sheikh Raisuddin, Brijesh K. Singh, Chetna Mishra |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Programmed cell death Apoptosis Mitochondria Liver DNA Fragmentation Pharmacology Mitochondrion Toxicology Rats Sprague-Dawley Bcl-2-associated X protein medicine Animals Cells Cultured bcl-2-Associated X Protein Membrane Potential Mitochondrial chemistry.chemical_classification Sulfonamides Reactive oxygen species biology Plant Extracts Chemistry Fumaria Cytochrome c Cytochromes c General Medicine Chromatin Assembly and Disassembly Glutathione Genes bcl-2 Rats Biochemistry Hepatoprotection Cyclooxygenase 2 Hepatocytes biology.protein Lipid Peroxidation Reactive Oxygen Species Nimesulide medicine.drug |
| Zdroj: | Toxicology in Vitro. 24:495-508 |
| ISSN: | 0887-2333 |
| Popis: | Nimesulide, a popular nonsteroidal anti-inflammatory drug, has been associated with serious hepatotoxicity. Reactive oxygen species (ROS) and mitochondrial perturbations have been implicated in drug induced hepatotoxicity, although their role in the pathway needs exploration. Study was undertaken to elucidate the effect of Fumaria parviflora Lam. (Fp) on nimesulide induced cell death in primary rat hepatocyte cultures. Fp extract treated cells showed increased viability as compared to nimesulide stressed cells as assessed by MTT assay. LDH leakage increased significantly at 500microM nimesulide, and the data suggested that apoptosis was the predominant mechanism responsible for cell death. Nimesulide induced apoptosis was further confirmed by DNA fragmentation and chromatin condensation. Nimesulide exposure increased intracellular ROS, translocation of Bax and Bcl2 followed by mitochondrial depolarization and cytochrome c (Cyt c) release along with caspase-9/-3 activity confirming involvement of mitochondria in nimesulide induced apoptosis. Events like membrane depolarization of mitochondria, expression of Bax, Bcl2, externalization of phosphatidyl serine are substantially reversed by the pre-treatment of Fp extract. Thus, the study indicates that Fp extract modulates critical events regulating pro and anti-apoptotic proteins in mitochondria dependent apoptosis induced by nimesulide. |
| Databáze: | OpenAIRE |
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