Protective effects of Cornus Mas fruit extract on methotrexate-induced alterations in mice testicular tissue: Evidences for histochemical and histomorphometrical changes in an animal model study

Methotrexate (MTX) as a chemotherapeutic agent, has adverse effects on reproductive organs by enhancing oxidative stress. In this study, the protective effects of Cornus mas fruit extract (CMFE) against MTX side effects were evaluated. Forty-eight mature male NMRI mice were divided into six groups: group 1 (control) received 0.10 mL per day of normal saline intraperitoneally (IP), group 2 received MTX (20 mg kg-1 per week, IP), group 3 received MTX along with CMFE 250 mg kg-1 per day by oral gavage, group 4 received MTX along with CMFE 500 mg kg-1 per day by oral gavage, group 5 received MTX plus 1000 mg kg-1 per day of CMFE by oral gavage, and group 6 received 1000 mg kg-1 per day of CMFE extract, orally. All animals were treated for 35 consecutive days. Thickness of testicular capsule and germinal epithelium and diameter of seminiferous tubules were measured. Intra-cytoplasmic levels of carbohydrate, unsaturated fatty acid (UFA) and alkaline phosphatase were assessed. Serum level of testosterone and testicular total antioxidant capacity (TAC) were also evaluated. The results demonstrated that MTX administration caused morphometrical parameters except the thickness of testicular capsule were significantly different in comparison to control group and decreased cytoplasmic concentration of carbohydrate in the first three layers of germinal epithelium and increased the UFA levels. Contrarily, CMFE ameliorates the condition. Moreover, CMFE increased testosterone level and increased the MTX-reduced TAC level. In conclusion, it was revealed that CMFE decreased the cellular atrophy by controlling the energy substrate utilization based on lipids and carbohydrates via provoking the testicular antioxidant status.