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Depression of hepatic mixed-function oxidase activity by B. pertussis in splenectomized and athymic nude mice
Abstract:
Administration of Bordetella pertussis (B. pertussis), Corynebacterium parvum (C. parvum), and several other immunoactive substances is known to cause a marked decrease in the activity of the hepatic microsomal mixed-function oxidase system. The effect of C parvum has been reported to involve the reticuloendothelial system. In the present study, the effect of B. pertussis administration to decrease hepatic microsomal drug metabolism was studied in unoperated, sham-operated, and splenectomized mice as well as in athymic nude (nu/nu) mice and their phenotypically heterozygous (+/nu) littermates. Administration of B. pertussis to the splenectomized, sham-operated, and unoperated mice resulted in a decrease in the activity of the microsomal enzyme system that was approximately the same for each of the three groups of animals. Administration of B. pertussis to nu/nu mice and the +/nu mice also decreased the microsomal enzyme activity measured 24 hr after injection. However, at 7 days after B. pertussis administration, the hepatic drug-metabolizing activity of the nu/nu mice was not significantly different from control values, whereas the activity of the +/nu mice was still significantly depressed. The failure of splenectomy to prevent the decrease in microsomal mixed-function oxidase activity caused by B. pertussis indicated that the effect of this agent differs from that of C. parvum, whose effect was prevented by splenectomy. Indeed, the results obtained with the athymic nude mouse suggests that the depression of hepatic mixed-function oxidase activity by B. pertussis may involve T-cell dependent responses.
Insights
Bordetella pertussis (B. pertussis) reduces hepatic drug metabolism, with this effect potentially involving T-cell dependent responses in mice. Unlike Corynebacterium parvum, splenectomy does not prevent this B. pertussis-induced decrease in enzyme activity.
Area of Science:
- Immunology
- Pharmacology
- Hepatology
Background:
- Immunoactive substances like Bordetella pertussis (B. pertussis) and Corynebacterium parvum (C. parvum) can decrease hepatic microsomal mixed-function oxidase activity.
- The mechanism of C. parvum's effect is thought to involve the reticuloendothelial system.
Purpose of the Study:
- To investigate the role of the spleen and T-cells in the B. pertussis-induced decrease in hepatic drug metabolism.
- To differentiate the mechanism of B. pertussis from C. parvum's effect on hepatic enzymes.
Main Methods:
- B. pertussis was administered to unoperated, sham-operated, and splenectomized mice.
- The study also utilized athymic nude (nu/nu) mice and their heterozygous (+/nu) littermates.
- Hepatic microsomal drug metabolism activity was measured at 24 hours and 7 days post-administration.
Main Results:
- Splenectomy, sham-operation, or no operation did not prevent the decrease in enzyme activity caused by B. pertussis.
- B. pertussis administration decreased enzyme activity in both nu/nu and +/nu mice at 24 hours.
- At 7 days, enzyme activity recovered in nu/nu mice but remained depressed in +/nu mice.
Conclusions:
- The effect of B. pertussis on hepatic drug metabolism differs from C. parvum, as splenectomy does not prevent it.
- The results suggest that T-cell dependent responses may be involved in the depression of hepatic mixed-function oxidase activity by B. pertussis.