Depression of hepatic cytochrome P-450-dependent mixed function oxidases during infection with encephalomyocarditis virus

Infection of mice with encephalomyocarditis virus had a marked effect on drug biotransformation in the liver. the levels of cytochrome P-450 and cytochrome b₅ and aminopyrine N-demethylase activity were significantly decreased 3 days after the administration of lethal and sublethal doses of virus. Interferon was detected in serum at doses of virus that produced decreased drug biotransformation. Cytochrome P-450 content and aminopyrine N-demethylase activity remained at normal levels for the first 2 days following infection before reaching a maximum decrease on days 3 and 4. Concentration of interferon in the serum of infected mice appeared on day 2 of infection and reached peak levels on day 3. Increased heme oxygenase activity was associated with the decrease in cytochrome P-450 level during the infection. These studies indicate the existence of an interaction between virus infection and cytochrome P-450-dependent drug biotransformation. This may cause adverse toxic effects during the use of drugs that depend on the hepatic mixed function oxidases for elimination.