Alterations in hepatic biochemistry of mice intoxicated with MIC, carbaryl and thiram.
The effect of different doses of methyl isocyanate (MIC), carbaryl and thiram on liver microsomal mixed-function oxygenases (MFO) was studied in adult Swiss Portan mice by intraperitoneal (i.p.) injection for different durations. The LD50 dose of all three toxicants after 0.75 h of administration could increase cytochrome P-450 and cytochrome b5 contents (82-143%), and the 1/4 LD50 of these compounds could elicit the same effect after 168 h (168-393%). The 1/4 LD50 dose of thiram decreased the cytochrome P-450 content below the control level (69.62%) in 0.75 h and the same dose of MIC could decrease the cytochrome P-450 level by 40% compared to the control after 3 days of consecutive injection. The activities of drug-metabolizing enzymes (aminopyrine demethylase--NADH and NADPH-linked--and aniline hydroxylase) were found to increase with all three compounds in general. Marked changes in the activity of the marker enzyme glucose-6-phosphatase were also seen after i.p. injection if MIC, carbaryl and thiram. These findings suggested that these compounds were hepatotoxic, which could be due to their carbamylating nature.
Department of Biochemistry, Panjab University, Chandigarh, India.
M
M
Gupta
M K
MK
Amma
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D000986:Antisickling Agents / Q000633:toxicity*; D012721:Carbaryl / Q000633:toxicity*; D003485:Cyanates / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D005260:Female; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D017953:Isocyanates; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D013893:Thiram / Q000633:toxicity*
D000986:Antisickling Agents; D003485:Cyanates; D017953:Isocyanates; D013893:Thiram; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; C008461:methyl isocyanate; D006899:Mixed Function Oxygenases; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D005952:Glucose-6-Phosphatase; D012721:Carbaryl