Protective Effect of Misoprostol on Ibuprofen-In-duced Alteration of Testes Stereological Structure in Adult Male Mice

Background: Misoprostol, a prostaglandin E1 analog, is used clinically during treatment of duodenal and gastric ulcers with non-steroidal anti-inflammatory drugs such as ibuprofen to in-hibit acid secretion and stimulate bicarbonate and mucus secre-tion. It is well known that long time administration of ibuprofen can reduce sperm parameter and testosterone level but there is no study about effect of ibuprofen on structure of testis. This study was conducted to evaluate the structure of testis after long time administration of ibuprofen and protective effect of misoprostol on ibuprofen-induced alterations in testis tissue of adult male mice.Materials and Methods: In this study, 80 adult male mice were divided into 8 groups including: control, ibuprofen treated group which received 6 mg/Kg/day ibuprofen, three misopros-tol treated groups which received 1, 10 and 100 µg/Kg/day mis-oprostol and three ibuprofen+misoprostol treated groups which received 6 mg/Kg/day ibuprofen with 1, 10 and 100 µg/Kg/day misoprostol. All treatments were carried out for 40 consecutive days by oral gavage. At the end of experiment, animals were euthanized and their left testis were removed and fixed in 10% neutral buffered formalin. Tissues were processed by standard paraffin embedding and serially sectioned at 20 µm thickness. Twenty to twenty-five selected sections by systematic random sampling were stained with H&E and total volume of testis, germinal epithelium, interstitial tissue, and total numbers of spermatogenic, Sertoli and Leydig cells were estimated by point counting method based on Cavalieriʼs principle and optical dis-sector technique using by stereo-investigator software. Finally, one-way ANOVA and Tukey s post-hoc were performed for data analysis.Results: Results showed that ibuprofen reduced total volume of germinal epithelium and total number of all spermatogenic cells, Sertoli cells and Leydig cells and also increased intersti-tial tissue significantly compared to control group. Our results indicated that misoprostol could inhibit the ibuprofen-induced alterations in a dose dependent manner. Stereological studies revealed that misoprostol increased total volume of germinal epithelium of seminiferous tubules and total number of sper-matogenic cells, Sertoli and Leydig cells as well as decreased total volume of interstitial tissue significantly compared to ibu-profen treated group.Conclusion: Based on our results it can be concluded that ad-ministration of misoprostol can improve structure of testis after ibuprofen administration and can be considered as a suitable protective strategy for improvement of male infertility or sub-fertility due to NSAIDs administration.

کلیدواژه ها:

Misoprostol ، Prostaglandin E ، Ibuprofen ، Testis ، Ste-reology