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1996-02-26
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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).