Document Detail

Phenotype of hepatic xenobiotic metabolizing enzymes and CYP450 isoforms of sanguinarine treated rats: effect of P450 inducers on its toxicity.
MedLine Citation:
PMID:  19788401     Owner:  NLM     Status:  MEDLINE    
Catalytic and immunochemical activities of cytochrome P450 (CYP) isoforms were investigated in argemone alkaloid, sanguinarine (SAN) intoxicated rats, pre-treated with different CYP inducers. SAN treated control (CON) and ethanol (ET), 3- methylcholantherene (MC) or dexamethasone (DEX) pre-exposed rats, resulted in 48, 64, 47 and 33% decrease in CYP content. SAN exposure to CON, and DEX, MC or ET pre-treated animals caused a decrease (22-37%) in glutathione-S-transferase (GST) activity, however, quinone reductase (QR) activity decreased (26-45%) in the MC pre-exposed group. Similarly, western-blot analysis of hepatic CYP1A1 and CYP1A2 showed a decrease (27-37%) in MC pre-treated SAN exposed animals. Further, a decrease in mortality in the SAN+MC (25%) group compared to SAN treated animals was also observed. The results suggest that inhibition of CYP 1A1, 1A2, 2D1, 2E1, 3A1, and Phase II enzymes by SAN augments its toxicity, whereas attenuation of SAN toxicity by MC may be due to removal of parent compound/metabolites from the body.
Naveen Reddy Eruvaram; Mukul Das
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology mechanisms and methods     Volume:  19     ISSN:  1537-6524     ISO Abbreviation:  Toxicol. Mech. Methods     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-12     Completed Date:  2010-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101134521     Medline TA:  Toxicol Mech Methods     Country:  England    
Other Details:
Languages:  eng     Pagination:  510-7     Citation Subset:  IM    
Food Toxicology Division, Indian Institute of Toxicology Research (Formerly, Industrial Toxicology Research Centre), Council of Scientific and Industrial Research, Lucknow, India.
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MeSH Terms
Argemone / chemistry
Benzophenanthridines / analysis,  isolation & purification,  toxicity*
Cytochrome P-450 Enzyme System / biosynthesis,  metabolism*
Cytochromes b5 / biosynthesis
Enzyme Induction
Glutathione Transferase / biosynthesis
Isoquinolines / analysis,  isolation & purification,  toxicity*
Metabolic Detoxication, Drug / genetics*
Microsomes, Liver / enzymology
NAD(P)H Dehydrogenase (Quinone) / biosynthesis
NADPH-Ferrihemoprotein Reductase / biosynthesis
Plant Oils / chemistry
Rats, Wistar
Reg. No./Substance:
0/Benzophenanthridines; 0/Isoenzymes; 0/Isoquinolines; 0/Plant Oils; 0/argemone oil; 2447-54-3/sanguinarine; 9035-39-6/Cytochromes b5; 9035-51-2/Cytochrome P-450 Enzyme System; EC Reductase; EC Dehydrogenase (Quinone); EC Transferase

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