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العنوان
Protective effect of folic acid on uterine tube mucosal damage caused by methotrexate in adult female rats /
المؤلف
Ismael, Zahraa Mohammed.
هيئة الاعداد
باحث / زهراء محمد اسماعيل
مشرف / محمد احمد دسوقي
مشرف / ضحي صابر محمد
dahi_ahmed@med.sohag.edu.eg
مشرف / سلوي محمد عويس
salwa_youssif@med.sohag.edu.eg
مناقش / رضا عوض الله صالح
مناقش / درية عبدالله محمد زغلول
الموضوع
Folic Acid therapeutic use. Rats.
تاريخ النشر
2015.
عدد الصفحات
103 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
تشريح
تاريخ الإجازة
24/5/2015
مكان الإجازة
جامعة سوهاج - كلية الطب - التشريح والاجنة
الفهرس
Only 14 pages are availabe for public view

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Abstract

Methotrexate (MTX) was first developed in the 1940 ( as a specific antagonist of folic acid) , is mainly used in the treatment of malignant tumors .It has also been found to have a major therapeutic role in non-neoplastic diseases as an anti-inflammatory and immunosuppressive, widely used in the therapy of various types of diseases. It is used in the treatment of psoriasis, psoriatic arthritis, acute lymphoblastic leukemia and ectopic pregnancy.
Morbidities such as failed pregnancy and recurrent ectopic pregnancy have been attributed to the adverse effects of MTX on the fallopian tube. Previous studies declared that use of folic acid (FA) helped to limit the systematic toxicity of MTX.
The aim of this research was to study the effects of Folic acid on Methotrexate-induced derangement of the fallopian tube, as determined by observation of structural differences by using light and electron microscope.
18 adult female rats were used & divided into 3 groups;
1-the 1st group the control was given normal saline.
2- The 2ndgroup was given methotrexate 5mg/kg daily intraperitoneal injection.
3- The 3rd group was given methotrexate with administration of folic acid (0.1 mg/kg) intraperitoneal injection 24hrs after methotrexate injection.
The doses were be given intraperitoneal injection for 10 days, then the animals were been sacrificed by cervical dislocation, the ampulla of uterine tube was taken.
Sample was cut and fixed in formalin, dehydrated by passing in ascending grades of alcohols and embedded in paraffin wax. Then the sections were cut by thickness of 5µ & stained with H &E stains for examination of general histological structures using light microscope.
For electron microscopy examination; small pieces of ampulla of uterine tube was emerssed in gluteraldehyde and proceeded for electron microscopic examination. Ultrathin sections were taken to examine the ultrastructure .
Thereby, the following findings were observed:
Rats treated with methotrexate only with light microscope showed; loss of the normal architecture of mucosa of ampulla of the uterine tube, some areas of ulceration with detached mucosa into the lumen, high numbers of secretory cells were swollen others ruptured, and the remaining of cells appeared flattened, the lamina propria showed dense accumulations of infilammatory cells, The musculosa showed multiple discontinuations in the inner circular layer. Some areas of haemorrage observed in the outer longitudinal layer and in the serosa.
With transmission electron microscope; the epithelial cells showed cilial loss, with cytoplasmic vacuolations and destruction of its organelles, some nuclei showed fragmentation, destruction and pyknosis, loss of intercellular junctions and the basement membrane was irregular. The lamina propria showed infiltration by numerous inflammatory cells (esinophils, dendritic cells).The smooth muscle layer showed also marked vacuolations and destruction of their cytoplasm, the nuclei were small and deeply stained.
After treatment with folic acid the rats showed signs of improvement: The epithelium appeared intact, the cytoplasm less vacuolated, the nuclei were near normal .The lamina propria appeared nearly normal with less or no inflammatory cells, no blood vessels congestion .The smooth muscle showed less cytoplasmic vacuolations, the nuclei appeared normal.
With transmission electron microscope: The epithelial cells showed intact cells with less cilial loss, less cytoplasmic vacuolations and less destruction of their organelles, nuclei were euchromatic , no loss of the intercellular junctions and the basement membrane was nearly similar to control group .
The lamina propria showed less or no infiltration by inflammatory cells. The smooth muscle layer showed also less vacuolations of their cytoplasm, the nuclei were euchromatic.
Conclusion:
In conclusion to the previous results;
• Methotrexate causes derangement of tubal epithelium and destruction of its cells.
• Folic acid is useful in Methotrexate-induced derangement of tubal epithelium.
Recommendation:
It is recommended adding folic acid to methotrexate in treatment of cancer or unruptured ectopic pregnancy.
More researches are needed to evaluate the effect of folic acid on derangement of the tubo-ovarian ultrastructural architecture caused by methotrexate.