The protective role of zinc and N-acetylcysteine in modulating zidovudine induced hematopoietic toxicity.
The role of zinc and N-acetylcysteine (NAC) has been investigated in protecting the hematopoietic progenitor cells from zidovudine (AZT)-induced toxicity. Murine bone marrow progenitor cells (BMPC, 1x10(6)) were exposed to various concentrations (0.1-50 microM) of AZT in the presence and absence of zinc acetate (100 microM) or NAC (100 microM). The cell survival was determined by the colony forming assays of erythroid (CFU-E) and granulocytic (CFU-GM) lineage. The IC50 values of AZT in the presence of zinc were increased approximately 3-fold (from 3.0 to 9.5 microM) in the CFU-E assay and 7-fold (from 4.3 to 28.8 microM) in the CFU-GM assay whereas in the presence of NAC, the IC50 values were increased by 2- and 4-fold, respectively. To delineate the mechanism of significant protection of BMPC by zinc, the mRNA levels of metallothionein (MT) were monitored by using a 31-mer cDNA probe. Zinc produced a concentration-dependent increase in the MT mRNA levels in BMPC. These results suggest that zinc and NAC dietary supplementation can be conveniently used to reduce AZT-induced bone marrow toxicity.
Gogu
S R
SR
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Agrawal
K C
KC
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051379:Mice; D015215:Zidovudine / Q000009:adverse effects*; D015032:Zinc / Q000494:pharmacology / Q000627:therapeutic use*
D000931:Antidotes; D015215:Zidovudine; D015032:Zinc; D000111:Acetylcysteine