Document Detail


Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro.
MedLine Citation:
PMID:  21420465     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cadmium (Cd) is one of the ubiquitous environmental pollutants and is responsible for various organ pathophysiology including hepatic disorders. It is extremely toxic even in low concentrations and bioaccumulate in organisms. The present study has been carried out to investigate the cytoprotective role of arjunolic acid (AA), a tri terpenoid saponin, against Cd induced oxidative impairment and cell death in murine hepatocytes. Administration of cadmium (30μM), in the form of chloride (CdCl(2)) for 2 hr, significantly enhanced the ALT, ALP and LDH leakage, increased reactive oxygen species (ROS) production, reduced hepatocytes viability and altered the antioxidant status of hepatocytes by reducing intracellular GSH level, anti-oxidant enzymes activity and increasing intracellular GSSG and lipid peroxidation. Evidence for Cd-induced nature of cell death was sought by flow cytometric analysis. Signal transduction studies revealed that Cd markedly increased the levels of caspase-9, -8, -3, Fas and Bid, decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol, disturbed the Bcl-2 family protein balance, cleaved PARP protein and ultimately led to apoptotic cell death. Results showed that Cd could trigger both intrinsic and extrinsic apoptotic pathways. In addition, Cd markedly increased NF-κ≡ nuclear translocation in association with IKKα/β phosphorylation and IκBα degradation. Simultaneous treatment with AA (200μM), however, reduced Cd-induced oxidative stress, attenuated the nuclear translocation of NF-κ≡ and protects the hepatocytes from Cd-induced apoptotic death. Combining, data suggest that Cd-induced hepatic dysfunction and apoptosis might be supported by the ROS formation and mediated via the activation of NF-κ≡. AA treatment, on the other hand, reduced Cd-induced oxidative stress, attenuated the activation of NF-κ≡ and mitochondrion-dependent and independent apoptotic signalling pathways.
Authors:
Sankhadeep Pal; Pabitra Bikash Pal; Joydeep Das; Parames C Sil
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-17
Journal Detail:
Title:  Toxicology     Volume:  -     ISSN:  1879-3185     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ireland Ltd.
Affiliation:
Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054, INDIA.
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