Effect of famotidine on radiation induced apoptosis in human peripheral blood leukocytes

ABSTRACT

Radioprotective effects of famotidine, an antagonist of H2 receptor clinically used for peptic ulcer treatment, was previously shown on radiation-induced micronuclei and chromosomal aberration in human peripheral blood lymphocytes and mouse bone marrow cells. This study was conducted to investigate radioprotective property of famotidine against radiation induced apoptosis in human peripheral blood leukocytes. Peripheral blood was obtained from 6 healthy volunteers including three males and three females. 12 microL of blood sample diluted in 1 ml RPMI-1640 supplemented with antibiotics and foetal calf serum was irradiated a dose of 8 Gy gamma rays generated from a Co-60 source at a dose rate of 1.27 Gy/min. After 48 h incubation in a 37 ?C incubator, cells embedded in low melting point agarose were transferred to a slide precoated with normal agarose. Cells were lysed and subjected to electrophoresis under neutral condition. Slides were then stained with ethidium bromide and analysed under a fluorescence microscope. 500 cells were analysed for each sample for the presence of apoptosis. The data were statistically evaluated using Man-Whitney non-parametric and ANOVA tests. Results show a significant increase in apoptosis induction following 8 Gy gamma-irradiation comparing with controls [p<0.001]. The presence of famotidine at 50 and 100 microg/ml did not show any protective effect against radiation induced apoptosis; however, the presence of famotidine at higher concentration [200 microg/ml] significantly deceased radiation induced apoptosis [p<0.001]. The obtained results suggest that famotidine suppresses radiation-induced apoptosis at 200 microg/ml, probably via OH radical scavenging and an intracellular antioxidation mechanism. Famotidine appears to be a useful candidate for the future development of post-irradiation radioprotectors