The Study of Teratogenic and Histological effects of treatment with Methotrexate and Rituximab in Swiss White Mice

Abstract

The present study was conducted to evaluate teratogenic and histopathological effects of two drugs Methotrexate (MTX) and Rituximab (RTX) ) in Swiss white mice Mus musculus by intra-peritoneal injectioning at 9 day after gestation, sacrificing of pregnant females at 18 day of pregnancy to study features abnormalities of embryos. (Liver, Kidney and Heart) of pregnant and non pregnant females of mice (Lungs and spleen) of pregnant females used in Histopathological study. The results showed that abortion caused by MTX at 5, 10 mg/kg bw., RTX at 10 mg/kg bw., and 5 mg/kg bw MTX +5 mg/kg bw RTX. The treatment with RTX at 5 mg/kg bw. induces features of skeletal abnormalities in embryos of treated pregnant females. When the pregnant females treated with the both drugs embryos of treated females showed abnormalities in neck, lumbar vertebrae, skull bones and tail vertebrae. Histopathological effects, represented as desquamation in epithelium of kidney tubules, hemorrhage, congestions, infiltration of lymphocytes, necrosis and apoptosis of cells in liver, kidney, spleen, and lungs, damage of alveolar wall, enlargement of heart cells and increasing of nuclei, in treated pregnant females was more than that of non pregnant females. The current study suggest that MTX and RTX had genotoxic and cytotoxic effects, based on indication that 5, and 10 mg/kg.b.wt of MTX, 10 mg/kg b.wt. of RTX and 5 mg/kg bw MTX +5 mg/kg bw RTX caused abortion, 5 mg/kg b.wt. of RTX caused teratogenic features. Treatment with the two drugs simultaneously has less impact on development of embryos as we found no abortion but it caused histopathological effects and congenital abnormalities.