Docosahexaenoic Acid Reduces Cyto-Genotoxicity of Cytosine Arabinoside in Normal Mouse Bone Marrow

Abstract

Aims: This paper evaluates the use of percentage of micronucleus (MN), polychromatic erythrocytes (PCEs), chromosomal aberration (CA) and mitotic index (MI) frequencies in mice bone marrow smears as a method for assessing the ability of docosahexaenoic acid (DHA, is an omega-3 fatty acid) to reduce cyto-genotoxicity damage of cytosine arabinoside (ara-C). Ara-C is widely prescribed antineoplastic drug, especially for the treatment of acute myeloid leukemia. It is a pyrimidine analog, in which the ribose sugar of cytidine is replaced by arabinose moiety. Methodology: Positive control group of mice was only given intraperitoneal dose of ara-C of 75 mg/kg (every 12 h for 5 days); this dose was selected in accordance with its human therapeutic values. Negative control group of mice group only received 0.1 ml sterile distilled water every 12 hours for 5 days. Three treatment groups of mice were given same dose of ara-C in addition to three different doses of DHA (125, 250 and 500 mg/kg of mice). Experimental data were analyzed using (Mann–Whitney U-test) to compare values of positive and negative controls. However, Kruskal–Wallis test followed by Dunn’s multiple comparisons test were used to compare values of treatments with positive control. All values were accepted at p = 0.05. Results: When 75 mg/kg ara-C was applied, positive control group showed a significant increase in MN and CA, a high decrease in PCE, and a significant decrease in MI. When DHA was used with ara-C, the picture is changed, particularly at a medium dose of DHA of 250 mg/kg where a decrease MN and CA and an increase in PCEs in addition to an increase in MI were observed. Conclusion: DHA at 250 mg/kg was able to reduce cytogenotoxicity of ara-C, and lead to protecting the normal proliferating cells in bone marrow from the damaging effect of ara-C and hence improving therapy by ara-C.