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Alterations in hepatic biochemistry of mice intoxicated with MIC, carbaryl and thiram
Abstract:
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.
Insights
Methyl isocyanate (MIC), carbaryl, and thiram exposure affects liver enzymes in mice. These chemicals show hepatotoxicity, potentially due to their carbamylating properties.
Area of Science:
- Toxicology
- Biochemistry
- Pharmacology
Background:
- Liver microsomal mixed-function oxygenases (MFO) are crucial for xenobiotic metabolism.
- Understanding the impact of toxicants on MFO is vital for assessing liver health.
- Methyl isocyanate (MIC), carbaryl, and thiram are industrial chemicals with known toxic potential.
Purpose of the Study:
- To investigate the effects of varying doses and durations of MIC, carbaryl, and thiram exposure on mouse liver MFO.
- To determine the dose-dependent and time-dependent responses of key liver enzymes to these toxicants.
- To evaluate the potential hepatotoxicity induced by these chemical agents.
Main Methods:
- Adult Swiss Portan mice were administered different doses of MIC, carbaryl, and thiram via intraperitoneal injection.
- Exposure durations varied to assess acute and sub-chronic effects.
- Liver microsomal fractions were analyzed for cytochrome P-450, cytochrome b5, and enzyme activities (aminopyrine demethylase, aniline hydroxylase, glucose-6-phosphatase).
Main Results:
- Acute LD50 doses of all three toxicants increased cytochrome P-450 and cytochrome b5 levels.
- Lower doses (1/4 LD50) also increased these cytochromes after prolonged exposure (168 hours).
- Thiram and MIC, at 1/4 LD50, decreased cytochrome P-450 levels after acute or sub-chronic exposure, respectively. Drug-metabolizing enzyme activities and glucose-6-phosphatase showed significant alterations.
Conclusions:
- MIC, carbaryl, and thiram exhibit dose- and time-dependent effects on mouse liver MFO.
- These compounds demonstrate hepatotoxicity, evidenced by changes in MFO components and enzyme activities.
- The observed hepatotoxicity is likely linked to the carbamylating nature of these chemicals.