The Study of Teratogenic and Histological effects of treatment with Methotrexate and Rituximab in Swiss White Mice
Main Article Content
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.
Article Details

This work is licensed under a Creative Commons Attribution 4.0 International License.
Tikrit Journal of Pure Science is licensed under the Creative Commons Attribution 4.0 International License, which allows users to copy, create extracts, abstracts, and new works from the article, alter and revise the article, and make commercial use of the article (including reuse and/or resale of the article by commercial entities), provided the user gives appropriate credit (with a link to the formal publication through the relevant DOI), provides a link to the license, indicates if changes were made, and the licensor is not represented as endorsing the use made of the work. The authors hold the copyright for their published work on the Tikrit J. Pure Sci. website, while Tikrit J. Pure Sci. is responsible for appreciate citation of their work, which is released under CC-BY-4.0, enabling the unrestricted use, distribution, and reproduction of an article in any medium, provided that the original work is properly cited.
References
[2] Strand V.; Kimberly, R. and Issacs J. D. (2007). Nature Reviews Drug Discovery:75-92.
[3] Keshava, C.; Keshava N.; and Wong W et al. (1998).Mutate Res;60:729-35.
[4] Looney, R.J.; Anolik, J. and Sanz I. (2004). B lymphocytes in systemic lupus erythromatuses in Looney RJ, Huggins J.(2006). Use of intravenous immunoglobulin G. Best Pract Res Clin Haematol;19:3–2.
[5]Reff, M. E.; Carner, K.; Chambers, K.S.; Chinn, P.C.; Leonard, J.E. and Raab, R.et al. (1994). Depletion of B-cells invivo by achimeric mouse human monoclonal antibody to CD20+. Blood. 83:435-45.
[6] Stanly, B.; Emery, C. P.; Greenwald, M. |W.; Dougados, M.; Furie, R.A.; Genovese, M.C.; Keystone, E. C.; Loveless J. E.; Burmester, G.; Cravets, M.W. Hessey, E.W.; Shaw T. and Mark C. Totoritis. (2006). Rituximab for Rhumatoid arthritis refractory to Anti- Tumer necrosis factor therapy. ACR. Vol. 54. No.9. PP2793-2806.
[7] Jarmalaite, S.; Dedonytė1, V.; Mierauskiene, J.; Simkutecot,L. J. Ranceva, J. and Butrimiene, I. (2008).Cytogenetic effects of treatment with methotrexate and infliximab in rheumatoid arthritis patients. BIOLOGIA.. 54. No. 1.PP. 7–11.
[8]Erdogan, D.; Kadiodla D. and Peker T.(1995). vsulisation of fetal skeletal system by double staining with alizarin red and alcian blue. Gazi Medical J. 6:55-8.
[10]King Edward Memorial Hospital (KEMH). (2016). Abnormalities of early pregnancy; Ectopic
pregnancy. Medical manegment of ectopic pregnancy .Rev.
[11]MacDonald, K.; Norman, W.V. and Popescu, O.(2013) New anomalies due to methotrexate and misoprostol exposure in early pregnancy. Brief communications.: wendy. norman@ubc.ca(W.V. Norman).
[12] Chakravarty, E. F.; Murray, E.R.; Kelman A. and Pamela F. (2010). Pregnancy outcomes following maternal exposure to rituximab. bloodjournal. hematologylibrary. org. doi: 10.1182/ blood - 2010-07-295444.
[13]Anderson, C.B.E. (1980). Murins Text book of pathology. British library cataloging in publication data, London.
[14]Krishna, V. (2004). Text book of pathology. 1st ed. Orient Longgman Private Limited. І ndia. Pp:538,564. [15] Laksin, D.L.; Laksin, J. D.(2001). Role of Macrophages and inflammatory mediators in chemically induced toxicity.Toxicology .160,pp:111-118.
[17]Patel, N. N.; Ghodasara, D. J.; Sunanda Pandey, Priya D. Ghodasara, J. H. Khorajiya, B. P. Joshi and C. J. Dave. (2014). Subacute toxicopathological studies of methotrexate in Wistar rats. Veterinary World, EISSN: 2231-0916.