Genotoxicity of ranitidine-Hcl histochemical cytogenetical and teratological study

ABSTRACT

Ranitidine-HCl is widely prescribed by Egyptian physicians as an acid-supperssing medication in patients with some gastrointestinal diseases. It is frequently continued when symptoms persist. The genotoxicity of ranitidine is controversial. In the present study, its genotoxicity was assessed after drenching pregnant mice [from the 6[th]-15[th] day of gestation] saline, half therapeutic, therapeutic or double therapeutic doses of ranitidine. Teratogenicity in the offspring were detected. Chromosomal aberration were assessed in bone marrow cells of the mothers, and the embryonic cells of the 18-day embryos. The DNA frequency distribution in mother's hepatocytes and placenta were measured and statistically analyzed. Teratogenic study indicated that ranitidine causes a dose related decrease in body weight and skeletal size. The cytogenetic data indicates that ranitidine administration results in a dose dependent increase in the total aberration in both mothers and embryos. The rate of increase in polyploidy in relation to the dose is higher in mothers than embryos. The frequency distribution of DNA in hepatocytes of pregnant mice shows that the population of cells in the sub G2 representing apoptotic cells, hyper G2 representing S-hase and aneupoloid cells, and polyploid cells are increasing in dose dependent fashion. Such changes were less pronounced in the cells of the placenta. In conclusion, oral administration of ranitidine-HCl results in genotoxic features especially in adult pregnant mice