Lepidium draba L. leaves extract ameliorated cyclophosphamide-induced testicular toxicity by modulation of ROS-dependent Keap1/Nrf2/HO1, Bax/Bcl2/p53/caspase-3, and inflammatory signaling pathways.

Abstract

The aim of this study was to evaluate the protective effects of Lepidium draba L. extract on cyclophosphamide (CP)-induced oxidative damages to testes in rats using sex hormones, antioxidant properties, inflammatory, and apoptotic pathways. Six groups of male Wistar rats (n=6/group) received distilled water (NC), CP (100mgkg-1 day-1 /intraperitoneal), CP with L. draba extract [100 (LDCP 100), 200 (LDCP 200), and 400 (LDCP 400) mg/kg/day/orally] and also only L. draba extract [400 (LD400) mg/kg/day/orally] in 35days. On day 36 of the study, sperm parameters, serum levels of sex hormones, antioxidant enzyme activity, nitric oxide levels, and inflammatory cytokines and also testicular tissue (ferric reducing antioxidant power and thiobarbituric acid reactive substances levels and expression of ROS-dependent pro/anti-apoptotic pathways) were evaluated. In L. draba-treated groups, especially doses of 200 and 400, in addition to improving sperm parameters and sex hormones (Increased levels of all three hormones luteinizing hormone, follicle-stimulating hormone, and testosterone), serum antioxidant (catalase, superoxide dismutase, and glutathione peroxidase activity increased and nitric oxide levels decreased), and anti-inflammatory properties (levels of IL-6, TNF-α, and IL-1β decreased and MIF and TGF-β increased) also showed modification. By strengthening the anti-apoptotic pathway of Keap1/Nrf2/HO1 and inhibiting the apoptotic pathway of Bax/Bcl2/p53/caspase-3, L. draba maintains the structure and function of testicular tissue so that eventually p53-positive testicular cells are reduced and Bcl-2-positive cells increased. L. draba can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti-inflammatory, and antioxidant pathways. PRACTICAL APPLICATIONS: Lepidium draba have considerable antioxidant properties and can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti-inflammatory, and antioxidant pathways. The present results are useful to find a suitable supplement for improving the sexual performance of patients treated with chemotherapy drugs.