Involvement of mitochondria mediated pathways in hepatoprotection conferred by Fumaria parviflora Lam. extract against nimesulide induced apoptosis in vitro.
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.
Tripathi
Madhulika
M
Herbal Research Section, Indian Institute of Toxicology Research (CSIR), P.O. Box-80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
Singh
Brijesh Kumar
BK
Mishra
Chetna
C
Raisuddin
Sheikh
S
Kakkar
Poonam
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D031312:Fumaria / Q000737:chemistry*; D019254:Genes, bcl-2; D005978:Glutathione; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D015227:Lipid Peroxidation; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013449:Sulfonamides / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein
D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005978:Glutathione; C012655:nimesulide