Tribulus terrestris Protects against Male Reproductive Damage Induced by Cyclophosphamide in Mice

Abstract

Tribulus terrestris (TT) has been considered as a potential stimulator of testosterone production, which has been related with steroidal saponins prevailing in this plant. Cyclophosphamide (CP) is the most commonly used anticancer and immunosuppressant drug, which causes several toxic effects, especially on the reproductive system. Patients who need to use CP therapy exhibit reduced fertility or infertility, which impacts both physically and emotionally on the decision to use this drug, especially among young men. We hypothesized that the treatment with TT dry extract would protect the male reproductive system against CP toxicity. Mice received dry extract of TT (11 mg/kg) or vehicle by gavage for 14 days. Saline or CP was injected intraperitoneally at a single dose (100 mg/kg) on the 14th day. Animals were euthanized 24 h after CP administration, and testes and epididymis were removed for biochemical and histopathological analysis and sperm evaluation. The dry extract of TT was evaluated by HPLC analysis and demonstrated the presence of protodioscin (1.48%, w/w). CP exposure increased lipid peroxidation, reactive species, and protein carbonylation and altered antioxidant enzymes (SOD, CAT, GPx, GST, and GR). Moreover, acute exposure to CP caused a reduction on 17 β-HSD activity, which may be related to the reduction in serum testosterone levels, histopathological changes observed in the testes, and the quality of the semen. The present study highlighted the role of TT dry extract to ameliorate the alterations induced by CP administration in mice testes, probably due to the presence of protodioscin.

Role of Antioxidant Natural Products in Management of Infertility: A Review of Their Medicinal Potential

“…Furthermore, cytotoxic cancer therapies such as cyclophosphamide have detrimental effects upon spermatogenesis [ 136 ]. Several natural products in this review were demonstrated as applicable reproductive agents, reducing the notorious effects of EDCs as well as chemotherapy such as mitomycin C, cyclophosphamide, cisplatin, and adriamycin [ 9 , 10 , 14 , 25 , 43 , 46 , 50 , 90 ]. Accordingly, the use of natural materials will be an effective alternative to prevent and treat infertility caused by oxidative stress due to increased exposure to chemicals.…”

“…In total, 75 studies focused on plant derived compounds, five studies on animal derived compounds, and only one study presented a natural substance of fungal origin. Natural products which were mentioned more than once include Curcumin, Echinacoside, and extracts from Cistanche tubulosa , Date palm pollen, Diallyl sulfide , Lycium barbarum , Linn., Lepidium meyenii Walp., Morinda oleifera Lam, and Tribulus terrestis Linn [ 6 , 9 , 22 , 50 , 51 , 54 , 55 , 63 , 64 , 65 , 104 , 105 ]. Especially, the effects of Tribulus terrestis Linn.…”

“…Especially, the effects of Tribulus terrestis Linn. were elicited by in vivo and clinical studies, showing improved sperm motility and spermatozoa performance [ 9 , 104 , 105 ]. Most experiments examined the structural and functional properties of sperm, such as concentration, motility, and morphology, which are reported as provable reference values by the World Health Organization [ 154 ].…”

“…Excessive production of ROS in reproductive tract can both damage the fluidity of sperm plasma membrane and the integrity of DNA in sperm nucleus, which can lead to spermatogenesis dysfunction and toxic effects on sperms, causing the lipid peroxidation of sperm membrane [ 8 ]. Such peroxidation exercises deterious influences and leads to serious pathological changes and infertility [ 9 ]. Differentiation of the sperms is dependent on the Leydig cells which secrete testosterone hormone [ 10 ].…”

“…Decreased level of LPO was also observed, supporting improvements of fertility actions by this natural compound. Tribulus terrestris Linn., a member of the Zygophyllaceace family is commonly used as a folk medicine for a broad range of diseases from impotence, rheumatism, hypertension, to kidney stones [ 9 ]. Pavin et al showed that Tribulus terrestris dry extract (11 mg/kg for 14 days) protected infertility in Swiss albino mice induced by cyclophosphamide, a famous anticancer drug.…”