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J Microsc Ultrastruct. 2018 Oct-Dec;6(4):192-196. doi: 10.4103/JMAU.JMAU_31_18.

Ultrastructural Alterations of Liver Tissue Cells in Methotrexate-Treated Balb/c Mice.

Author information

Department of Nursing, Faculty of Health Sciences, Ankara Yildirim Beyazit University, Ankara, Turkey.
Department of Biology, Faculty of Science, Ankara University, Ankara, Turkey.
Department of Biology, Faculty of Science and Art, Hitit University, Corum, Turkey.
Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey.



The current study investigated the efficacy of methotrexate (MTX) on liver tissue cells of Balb/c mice at the ultrastructural level using transmission electron microscopy.


This agent is well known and used as a chemotherapeutic agent for a long time and not selective for cancer cells so, healthy cells beside cancer cells are also affected by MTX.

Materials and Methods:

Experimental animals were divided into two groups; the first group was kept without treatment and served as the control, the second group was treated with 115 mg/kg MTX i.p. once weekly for 4 weeks and sacrificed under anesthesia after the 4th week. The liver tissues were osmium fixed and embedded in araldite, sectioned and observed under transmission electron microscope.


Normal cell ultrastructure was determined in the control group whereas the liver cells of the MTX-treated group revealed ultrastructural alterations, such as the increase in lipid droplets, discontinuity of rough endoplasmic reticulum cisternae and vacuole formation. In addition, the loss of cytoplasmic material in hepatocytes was also evident. Condensation of nuclear chromatin and fusion of nucleic membranes were observed in the liver cells of the treated group.


Results of the study indicated that MTX, used for different types of medical treatment, disturbed liver cell ultrastructure.


Hepatocyte; liver; methotrexate; transmission electron microscope; ultrastructure

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