Biochemical toxicology of argemone oil. I. Effect on hepatic cytochrome P-450 and xenobiotic metabolizing enzymes

J Appl Toxicol. 1991 Jun;11(3):203-9. doi: 10.1002/jat.2550110309.

Abstract

The in vivo effect of argemone oil on hepatic xenobiotic metabolizing enzymes was investigated in albino rats following either a single (10 ml kg-1 body wt.) or multiple intraparenteral doses (5 ml kg-1 body wt.) for three days. Animals sacrificed 72 h after a single intraparenteral dose of argemone oil exhibited a significant loss of hepatic cytochrome P-450 (35%) and cytochrome b5 (34%) contents and inhibition of aminopyrine-N-demethylase (APD), aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin-O-deethylase (ECD) activities (21-39%). Three successive 24-hourly intraparenteral injections of argemone oil followed by sacrificing the animals after 24 h of the last injection, showed a greater degree of inhibition of the content of cytochrome P-450 (58%) and its dependent mixed-function oxidases (35-63%). Also, multiple treatment of argemone oil caused a depletion of endogenous hepatic glutathione (GSH) content (72%) with a concomitant increase in lipid peroxidation (177%) and decrease in glutathione-S-transferase (GST) activity (30%). A significant decrease in relative liver weight (39%) was observed in animals treated with multiple treatment of argemone oil. These results suggest that argemone oil can alter both membrane and cytosolic defences and destabilizes the hepatic cytochrome P-450 dependent mixed-function oxidase system, so that it tips in the direction of autooxidative peroxidation of lipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cytochrome P-450 Enzyme System / drug effects*
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytochromes b5 / drug effects
  • Cytochromes b5 / metabolism
  • Glutathione / metabolism
  • Glutathione Transferase / drug effects
  • Glutathione Transferase / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / enzymology*
  • Liver / metabolism
  • Male
  • Plant Oils / toxicity*
  • Rats
  • Rats, Inbred Strains
  • Xenobiotics / metabolism

Substances

  • Plant Oils
  • Xenobiotics
  • argemone oil
  • Cytochromes b5
  • Cytochrome P-450 Enzyme System
  • Glutathione Transferase
  • Glutathione