Document 0088
 DOCN  M94A0088
 TI    Alterations of hepatic drug metabolism in mice following infection with
       the murine retrovirus LP-BM5.
 DT    9412
 AU    Ansher S; Thompson W; Watson R; Laboratory of Bacterial Toxins, Food and
       Drug Administration,; Bethesda, MD 20892.
 SO    Immunopharmacology. 1994 May-Jun;27(3):215-23. Unique Identifier :
       AIDSLINE MED/94350644
 AB    Infection of mice with the murine retrovirus mixture LP-BM5 caused a
       retroviral infection with many similarities to human HIV infection. We
       have reported alterations in hepatic drug metabolism which progressed
       during the course of this infection. Hexobarbital-induced sleep time
       increased 1.5-2.2-fold above uninfected controls after 10 to 19 weeks
       post infection. Inhibition of spectral cytochrome P-450 levels by 25 to
       30% was observed between 15 and 17 weeks post-infection, and there were
       changes in specific microsomal enzyme activities. The microsomal cocaine
       demethylase activity was reduced by 40%, whereas cytosolic enzyme
       activities were increased by 1.5-2.0-fold. These alterations may
       contribute to the altered metabolism of drugs of abuse reported in MAIDS
       mice. The mechanism for these alterations is not known, although the
       effects correspond temporally to reported infiltration of the liver with
       immunoblasts and plasma cells. This suggests a role for the immune
       system or for mediators released by cells of the immune system which
       could account for these observations. An understanding of the effects of
       infection on drug metabolism is important because of their impact on the
       efficacy and safety of drugs for use in AIDS patients).
 DE    Animal  Cocaine/METABOLISM  Cytochrome P-450/DRUG EFFECTS/METABOLISM
       Cytosol/DRUG EFFECTS/ENZYMOLOGY  Disease Models, Animal  Female
       Hexobarbital/PHARMACOLOGY  Human  Liver/DRUG
       EFFECTS/ENZYMOLOGY/IMMUNOLOGY/*METABOLISM  Mice  Mice, Inbred C57BL
       Microsomes, Liver/DRUG EFFECTS/ENZYMOLOGY  Murine Acquired
       Immunodeficiency Syndrome/IMMUNOLOGY/*METABOLISM  Sleep/DRUG EFFECTS
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).