Antioxidant, Anti-Inflammatory and Antiapoptotic Effect of Mirtazapine Mitigates Cyclophosphamide-Induced Testicular Toxicity in Rats

Abstract

Background and Objective: Cyclophosphamide (CP) is an anticancer drug that may result in organ toxicities, especially testicular toxicity.Mirtazapine (MTZ) is an antidepressant drug with antioxidant activities. Here in this study, the effect of the MTZ, silymarin or its combination against CP-induced testicular toxicity in rats was examined. Materials and Methods: Thirty male rats were classified into five groups: Group (1) represents the normal control group, group (2) represents the CP-treated group, group (3) represents the mirtazapine-treated group, group (4) represents the Silymarin-treated group and group (5) represent the combined mirtazapine and silymarin-treated group. Results: Compared to the normal control group, CP induced a significant decrease in testosterone, catalase, GSH, SOD, IL-10, eNOS, HO-1, Ki67 (IHC), Bcl-2 and a significant increase in MDA, ALK, IL-6, IL-1$ and TNF-" and iNOS. In addition, it altered the histological structure of the testis. Administration of MTZ, Silymarin, or its combinations significantly reverses CP-induced testicular toxicity and ameliorated histological changes of testis induced by CP administration. Conclusion: Results concluded that MTZ can protect against CP-induced testicular toxicity via its antiapoptotic, antioxidant and anti-inflammatory activities.