Hepatic microsomal alterations during Dipetalonema viteae infection in Mastomys natalensis

The multimammate rat, Mastomys natalensis was used as a model system to evaluate the chronic effects of infection by Dipetalonema viteae on hepatic mixed function oxidase activity. Total hepatic cytochrome P450 content and related total tissue mixed function oxidase activity were decreased to about 50% of control levels at patent phase of infection. The decrease in total tissue mixed function oxidase activity was due to a large decrease in cytochrome P450 concentration in the endoplasmic reticulum. Although the decrease in total liver monooxygenase activity in two substrates aniline and aminopyrine roughly paralleled the loss in cytochrome P450 content, several other microsomal enzyme markers not related to cytochrome P450 monooxygenation were elevated in proportion to total liver microsomal protein content. These results suggest that in M. natalensis during experimental filariasis, there is proliferation of hepatic cells with normal content of endoplasmic reticulum. Furthermore, there appears to be selective toxicity for hepatic cytochrome P450 and related monooxygenase activities. This may compromise the animal's ability to metabolize and dispose of other drugs to which the animals may be exposed in the course of infection.