       Document 0859
 DOCN  M9620859
 TI    Lithium and anti-viral drug toxicity: II. Further studies on the ability
       of lithium to modulate the hematopoietic toxicity associated with the
       anti-viral drug zidovudine (AZT).
 DT    9602
 AU    Kazim S; Townsley L; Hughes NK; Tse KF; Ling J; Scott K; Birch NJ;
       Gallicchio VS; School of Health Sciences, University of Wolverhampton,
       UK.
 SO    Rom J Physiol. 1993 Jul-Dec;30(3-4):231-9. Unique Identifier : AIDSLINE
       MED/96078488
 AB    Lithium is an agent capable of influencing many aspects of blood cell
       production, in particular, the formation of granulocytes. Because of
       this property, lithium has been demonstrated to be an effective agent
       whenever granulocyte production is either faulty or inadequate. The
       anti-viral drug zidovudine (AZT) has used been extensively in the
       treatment of acquired immune deficiency syndrome (AIDS). However, its
       effectiveness is limited because of the myelosuppression and bone marrow
       toxicity associated with its use. We have previously demonstrated that
       lithium, when combined with AZT in vitro with normal bone marrow cells
       or when administered in vivo to mice receiving dose-escalation AZT,
       reduced the myelosuppression and marrow toxicity of AZT significantly.
       We report here further studies designed to evaluate the extent of
       lithium's capacity to modulate AZT toxicity by investigating the ability
       of lithium to influence blood cell production when administered to
       normal mice during an initial exposure to AZT. C57BL6 were administered
       dose-escalation AZT (1.0 mg/ml and 2.5 mg/ml) for a period of 4-weeks in
       the presence or absence of lithium carbonate (1 mM). This was followed
       by an additional 4-week period during which mice received only AZT.
       Animals were analyzed on a weekly basis for their peripheral blood
       indices. Animals receiving dose-escalation AZT demonstrated anemia,
       thrombocytopenia, and neutropenia which was dose-related. During the
       period when animals received combination lithium/AZT, there was
       significantly less anemia, thrombocytopenia, and neutropenia as compared
       to the AZT controls.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Animal  Comparative Study  Female  Hematopoiesis/*DRUG EFFECTS
       Leukocyte Count/DRUG EFFECTS  Lithium/*PHARMACOLOGY  Mice  Mice, Inbred
       C57BL  Monocytes/CYTOLOGY  Neutrophils/DRUG EFFECTS  Platelet Count/DRUG
       EFFECTS  Support, Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.
       Zidovudine/*PHARMACOLOGY  JOURNAL ARTICLE

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

