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Increased susceptibility to parathion poisoning following murine cytomegalovirus infection
Abstract:
In mice treated with ordinarily sublethal doses of parathion 2 to 5 days postinfection with murine cytomegalovirus (MCMV) 50 to 100% mortality was observed. These mortalities appeared to be due to a decrease in the ability of infected mice to detoxify parathion. Pentobarbital-induced sleeping time was also enhanced 3 and 6 days postinfection and cytochrome P-450 concentrations were markedly depressed in mice tested 3 days after infection. MCMV-induced effects on sensitivity to parathion and pentobarbital did not appear to be directly attributable to liver infection since concentrations of virus in the liver persisted at maximum concentrations well beyond the time when sensitivity to these compounds returned to normal. The time frame during which enhanced sensitivity to parathion and pentobarbital was observed suggests that this sensitivity may have been caused by viral-induced interferon-mediated depression of cytochrome P-450.
Insights
Murine cytomegalovirus (MCMV) infection in mice increases susceptibility to parathion toxicity by impairing detoxification pathways. This heightened sensitivity is linked to viral-induced interferon impacting cytochrome P-450 levels.
Area of Science:
- Virology
- Toxicology
- Immunology
Background:
- Murine cytomegalovirus (MCMV) is a significant viral pathogen.
- Cytochrome P-450 enzymes are crucial for xenobiotic detoxification.
- Viral infections can modulate host metabolic enzyme activity.
Purpose of the Study:
- To investigate the impact of MCMV infection on the detoxification of parathion in mice.
- To determine the effect of MCMV on pentobarbital-induced sleeping time and cytochrome P-450 concentrations.
- To elucidate the mechanisms underlying MCMV-induced alterations in xenobiotic metabolism.
Main Methods:
- Mice were infected with MCMV at sublethal doses.
- Parathion toxicity and pentobarbital-induced sleeping times were assessed post-infection.
- Cytochrome P-450 concentrations were measured in infected mice.
- Viral loads in the liver were quantified.
Main Results:
- MCMV infection led to 50-100% mortality in mice treated with parathion.
- Enhanced sensitivity to parathion and pentobarbital was observed 2-6 days post-infection.
- Cytochrome P-450 concentrations were significantly depressed 3 days post-infection.
- MCMV-induced sensitivity was not directly correlated with liver viral load.
Conclusions:
- MCMV infection impairs the ability of mice to detoxify parathion.
- Viral-induced interferon-mediated depression of cytochrome P-450 likely causes enhanced sensitivity to xenobiotics.
- These findings highlight the complex interplay between viral infections and host drug metabolism.