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).
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)
Kazim
S
S
School of Health Sciences, University of Wolverhampton, UK.
Townsley
L
L
Hughes
N K
NK
Tse
K F
KF
Ling
J
J
Scott
K
K
Birch
N J
NJ
Gallicchio
V S
VS
D000818:Animals; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D007958:Leukocyte Count / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology*
D015215:Zidovudine; D008094:Lithium