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.
Gupta
M
M
Department of Biochemistry, Panjab University, Chandigarh, India.
Amma
M K
MK
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