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, 1 × 10 6) were exposed to various concentrations (0.1–50 μM) of AZT in the presence and absence of zinc acetate (100 μM) or NAC (100 μM). The cell survival was determined by the colony forming assays of erythroid (CFU-E) and granulocytic (CFU-GM) lineage. The 1C 50 values of AZT in the presence of zinc were increased approximately 3-fold (from 3.0 to 9.5 μM) in the CFU-E assay and 7-fold (from 4.3 to 28.8 μM) in the CFU-GM assay whereas in the presence of NAC, the IC 50 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.