Berezhna L. Role of induction of cytochrome P-450 2E1 in pathogenesis of isoniazid hepatotoxicity

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0406U004010

Applicant for

Specialization

  • 14.03.06 - Токсикологія

11-10-2006

Specialized Academic Board

Д 26.550.01

Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine

Essay

The main point of this dissertation is an investigation of the role of the cytochrome P-450 2E1 induction in pathogenesis of isoniazid hepatotoxicity. This research proved the importance of complex approach for correction of cytochrome P-450 2E1 induction by its inductors, which can be a cause of liver injury. Direct correlation between p-nitrophenolhydroxylasе activity (cytochrome P-450 2E1 marker enzyme) in the rat liver and criterial indices of liver injury in case of using isoniazid was shown. In case of using the cytochrome P-450 2E1 selective inhibitor disulfiram combined with isoniazid, using of the biochemical and morphological methods, have proved a direct connection between an ability of the isoniazid to induce the cytochrome P-450 2E1 an its hepatotoxicity. The research showed the ability of experimental polyvitamin composition "MV" with metabolic action, which contain a bioactive substances to decrease the induction of the cytochrome P-450 2E1, show its antioxidant and hepatoprotective effect.

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