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http://nopr.niscpr.res.in/handle/123456789/23514| Title: | Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract |
| Authors: | Bagchi, Debasis Ra, Sidhartha D. Bagchi, Manashi Preuss, Harry G. Stohs, Sidney J. |
| Issue Date: | Jun-2002 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | To understand the bioavailability and mechanistic pathways of cytoprotection by IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) a series of in vitro and in vivo studies were conducted. Comparative protective abilities of GSPE, and vitamins C and E, singly and in combination, were assessed against smokeless tobacco extract (STE)-induced oxidative stress, DNA fragmentation and apoptotic cell death in a primary culture of normal human oral keratinocytes. GSPE protected against STE-induced oxidative stress, DNA damage and apoptotic cell death, and provided better protection as compared to vitamins C and E, singly and in combination. The bioavailability and protective ability of GSPE were examined against acetaminophen (AP)-induced hepato- and nephrotoxicity, amiodarone (AM)- induced lung toxicity, doxorubic in (DX)-induced cardiotoxicity and dimethylnitrosamine (DM)-induced spleenotoxicity in mice. GSPE fed animals were compared with GSPE-untreated mice to evaluate the protective ability of GSPE against these structurally diverse drugs/chemicals. Serum chemistry changes, histopathology and DNA damage were evaluated. Results indicate that GSPE preexposure prior to the drugs/chemicals such as AP, AM, DX or DM treatment, provided near complete protection in terms of serum chemistry changes and inhibition of both forms of cell death , e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced in GSPE-fed animals. Histopathological examination of multiple target organs provided similar data. The results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against structurally diverse drug- and chemical-induced toxic assaults. Further, these studies exhibited a series of mechanistic information including free radical scavenging ability, anti-endonucleolytic activity, cytochrome P450 2E l inhibitory activity, anti -necrotic, anti -apoptotic and anti -carcinogenic activities, modulatory effects on antioxidative and apoptotic regulatory genes such as Bcl2, c-myc and p53, which may be responsible for the novel chemoprotective properties exhibited by GSPE. |
| Page(s): | 717-726 |
| ISSN: | 0975-1009 (Online); 0019-5189 (Print) |
| Appears in Collections: | IJEB Vol.40(06) [June 2002] |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| IJEB 40(6) 717-726.pdf | 2.59 MB | Adobe PDF | View/Open |
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