Evaluation of the possible protective role of vitamin A on methotrexate-induced changes on the jejunal mucosa of adult male albino rat: Histological and immunohistochemical study

Methotrexate (MTX), a folic acid antagonist agent, is mainly used in treatment of malignant tumors and autoimmune diseases. Vitamin A is essential for normal growth and differentiation of epithelial tissues. The aim of this study was to evaluate the effect of methotrexate on the histological structure of jejunal mucosa and to assess the possible protective role of vitamin A. Fifty adult male albino rats divided into three groups; a control, vit A and experimental group subdivided into two groups (B and C), experimental group (B) received 4mg of methotrexate intraperitoneally as a single dose, and experimental group (C) received methotrexate and 1000IU of vitamin A given three days before MTX administration and continued until the rats were sacrificed. The specimens were prepared for histological, immunohistochemical and ultrastructure examination. Morphometric study was also done and statistical results were analyzed. Light and electron microscopic studies revealed structural alterations in group (B) in the form of disturbance of villus and crypt architecture. Dilatation of RER cisternae, swollen mitochondria with destroyed cristae vacuolation of the cytoplasm and lipid droplets in some cells were observed with widening of the intercellular space. Corrugation and indentation of the nuclear membrane and exfoliation of epithelial cells. PCNA showed a significant decrease in the number of PCNA-positive nuclei in the crypts of group B. Co-administration of vitamin A with methotrexate (group C) ameliorated these histological changes and there was a increase in the number of PCNA positive nuclei in the crypts. Methotrexate caused mucosal damage improved with vitamin A co-administration.