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In: Chemistry

The compound 4-methyl pyrazole (appropriate KI is 0.15 uM) is currently being used as a treatment...

The compound 4-methyl pyrazole (appropriate KI is 0.15 uM) is currently being used as a treatment for methanol poisoning. How would the effectiveness of 4-methyl pyrazole compare with the effectiveness of a formamide treatment (appropriate KI is 0.712 uM)?

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Expert Solution

Solution:

The effectiveness of 4-methyl pyrazole was already found by testing it in a rat samples.

Research work was made to determine whether 4-methylpyrazole inhibits the hepatotoxic effects of acetaminophen in a rat model. A nonblinded experiment using male Sprague-Dawley rats.

Animals were divided into four groups. Groups 1 through 3 received 2,000 mg/kg acetaminophen by gavage; group 4 acted as a control. At four or eight hours, group 2 received 400 mg/kg 4-methylpyrazole; group 3 received 50 mg/kg 4-methylpyrazole. Blood samples were taken for measurements of serum AST and ALT levels. Livers were removed for microscopic examination and grading of necrosis.

The result was Lower AST and ALT levels were obtained for both the 400-mg/kg (P < .01) and 50-mg/kg (P < .05) doses of 4-methylpyrazole administered four hours after acetaminophen. Although mean AST and ALT levels also were lower when 400 and 50 mg/kg 4-methylpyrazole were administered eight hours after acetaminophen, these results were not statistically significant. Median necrosis scores were 3 for rats receiving acetaminophen alone, 0.5 for those receiving acetaminophen and 400 mg/kg 4-methylpyrazole (P < .05), 1 for those receiving acetaminophen and 50 mg/kg 4-methylpyrazole (P < .05), and 0 for control rats (P < .05).

The Conclusion was made when administered four hours after a toxic dose of acetaminophen, 4-methylpyrazole significantly inhibits hepatotoxicity in the rat, as reflected by lower levels of serum transaminases and lesser degrees of hepatic necrosis.


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