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Hepatic microsomal cytochrome P450 system during experimental hookworm infection
B L Tekwani1, L M Tripathi, S Mukerjee
1Central Drug Research Institute, Lucknow, India.
Experimental and Molecular Pathology
|June 1, 1990
Summary
Hookworm infection selectively impairs liver cytochrome P450 function, affecting drug metabolism. This study reveals significant changes in hepatic mixed function oxidase activities and lipid accumulation in infected hamsters.
Area of Science:
- Hepatology
- Parasitology
- Biochemistry
Background:
- The liver's mixed function oxidase (MFO) system, particularly cytochrome P450 enzymes, is crucial for metabolizing xenobiotics.
- Hookworm infections can potentially disrupt host metabolic processes.
Purpose of the Study:
- To investigate the impact of Ancylostoma ceylanicum hookworm infection on the hepatic MFO system in golden hamsters.
- To assess alterations in cytochrome P450 content, enzyme activities, and related biochemical markers.
Main Methods:
- Experimental infection of golden hamsters with Ancylostoma ceylanicum.
- Measurement of hepatic microsomal cytochrome P450 content and specific enzyme activities (aminopyrine N-demethylase, benzo[a]pyrene hydroxylase, aniline hydroxylase).
- Analysis of other microsomal markers, hepatic lipid content, and in vivo drug metabolism indicators (hexobarbital sleeping time, zoxazolamine paralysis).
Main Results:
- A profound decline in hepatic microsomal cytochrome P450 content and activities of aminopyrine N-demethylase and benzo[a]pyrene hydroxylase.
- Significant accumulation of lipids (phospholipids, triglycerides, cholesterol) in hepatic tissue, leading to fatty necrosis.
- Impaired MFO activity confirmed by prolonged hexobarbital sleeping time and zoxazolamine paralysis.
- The MFO system retained responsiveness to chemical inducers, suggesting selective impairment.
Conclusions:
- Ancylostoma ceylanicum infection specifically impairs the hepatic microsomal cytochrome P450 system.
- Observed changes in MFO activity and lipid metabolism have significant implications for drug metabolism, toxicology, and pharmacology during parasitic infections.