Histological Evaluation of the Protective Effect of Stem Cell Derived Exosomes Versus Chitosan Nanoparticles on the Methotrexate Induced Testicular Injury in Albino Rat Model

Background and objectives: Methotrexate (MTX) is a chemotherapeutic agent used in the treatment of malignancies and autoimmune diseases. MTX testicular cytotoxicity has been proved in clinical and experimental studies. Therefore, this study was designed to compare the possible protective effect of adipose stem cells derived exosomes (ADSCs-EXOs) versus chitosan nanoparticles (CH-NPs) on methotrexate (MTX)-induced testicular injury in adult albino rats.
Materials and Methods: This study included 38 adult male albino rats and was divided into four groups in addition to the donor group. These groups included group I (Control) and three experimental groups; group II (MTX-treated rats); rats received IP injection of MTX (8mg/kg/week) for four weeks, group III (ADSCs-EXOs); rats were treated as group II concomitantly with IV injection of 1ml exosomes suspension (100μg/ml) once daily during the first seven days of the experiment, group IV (CH-NPs); rats were treated as group II concomitantly with chitosan nanoparticles (140 mg/kg/day) orally once daily for four weeks. Serum free testosterone level and testicular tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured. Testicular sections were stained with H&E, PAS, and iNOS & N-cadherin immunostaining. Morphometric measurements were compared between groups.
Results: Group II showed disorganized seminiferous tubules with obviously degenerated spermatogenic epithelium and absence of spermatozoa. Also, this was associated with significant decrease in serum testosterone level, tissue GSH level, spermatogenic epithelium height, seminiferous tubules diameter, and N-cadherin +ve immunoreaction, as well as significant increase in tissue MDA level and iNOS +ve immunoreaction. While groups III and IV showed restoration of the normal histological tissues, biochemical and morphometric parameters. Moreover, there was no significant difference between both groups.
Conclusion: Both ADSCs-EXOs and CH-NPs have proved their potent cytoprotective effects against MTX-induced testicular injury in adult male rats and their protective effects were almost similar.