Biochemical toxicology of argemone oil. I. Effect on hepatic cytochrome P-450 and xenobiotic metabolizing enzymes.
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.
Dyes and Food Adulterant Toxicology Lab., Industrial Toxicology Research Centre, Lucknow, India.
K K
KK
Upreti
M
M
Das
S K
SK
Khanna
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D015786:Cytochromes b5 / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D010938:Plant Oils / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D015262:Xenobiotics / Q000378:metabolism
D010938:Plant Oils; D015262:Xenobiotics; C030610:argemone oil; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D005978:Glutathione