[Cistanches tubulosa water extract protects the testis against cyclophosphamide-induced injury: Effect and mechanism].

ABSTRACT

OBJECTIVE: To investigate the protective effect of Cistanche tubulosa water extract (CTWE) against cyclophosphamide (CTX)-induced testis injury (TI) in mice and its action mechanism. METHODS: Thirty male mice were equally randomized into a normal control, a CTX-induced TI model control and a CTWE treatment group. After 7 days of adaptive feeding, the mice in the CTWE treatment group were treated intragastrically with CTWE at 10 g/kg/d, those in the normal control and TI model control groups with the same volume of normal saline qd all for 35 successive days, and those in the TI model control and CTWE treatment groups by intraperitoneal injection of cyclophosphamide at 80 mg/kg/d at 7, 14, 21, 28 and 35 days. Then all the animals were weighed, blood samples collected, and their testes and epididymides harvested for detection of the serum T content, examination of semen quality, measurement of testis weight, observation of histopathological changes in the testis, and determination of the levels of super oxide dismutase (SOD) and malondialdehyde (MDA) in the testis tissue and the mRNA expressions of the genes related to the nuclear factor erythroid-2-related factor (Nrf2) signaling pathway. RESULTS: The mice in the TI model control group, compared with the normal controls, showed significant decreases in the body weight (ï¼»34.13 ± 1.56ï¼½ vs ï¼»47.08 ± 1.98ï¼½ g, P < 0.05), testis weight (ï¼»81.82 ± 10.61ï¼½ vs ï¼»148.50 ± 14.82ï¼½ mg, P < 0.05), sperm concentration (ï¼»32.60 ± 5.29ï¼½ vs ï¼»78.90 ± 7.95ï¼½ ×106/ml, P < 0.05), sperm motility (ï¼»45.20 ± 7.09ï¼½% vs ï¼»86.70 ± 5.64ï¼½%, P < 0.05), serum T content (ï¼»7.49 ± 1.03ï¼½ vs ï¼»15.93 ± 1.36ï¼½ ng/L, P < 0.05), and SOD level (ï¼»152.22 ± 10.66ï¼½ vs ï¼»356.10 ± 30.95ï¼½ U/mg prot, P < 0.05), but remarkable increases in the percentage of morphologically abnormal sperm (MAS) (ï¼»39.30 ± 7.36ï¼½% vs ï¼»14.40 ± 3.53ï¼½ %, P < 0.05) and MDA level (ï¼»54.91 ± 5.12ï¼½ vs ï¼»31.71 ± 3.57ï¼½ nmol/mg prot, P < 0.05). The animals treated with CTWE, in comparison with the TI model controls, exhibited markedly increased body weight (ï¼»40.67 ± 2.13ï¼½ vs ï¼»34.13 ± 1.56ï¼½ g, P<0.05), testis weight (ï¼»121.21 ± 17.38ï¼½ vs ï¼»81.82 ± 10.61ï¼½ mg, P<0.05), sperm concentration (ï¼»58.40 ± 9.94ï¼½ vs ï¼»32.60 ± 5.29ï¼½ ×106/ml, P < 0.05), sperm motility (ï¼»72.30 ± 7.51ï¼½ % vs ï¼»45.20 ± 7.09ï¼½ %, P < 0.05), serum T content (ï¼»10.89 ± 1.07ï¼½ vs ï¼»7.49 ± 1.03ï¼½ ng/L, P < 0.05) and SOD level (ï¼»217.69 ± 24.59ï¼½ vs ï¼»152.22 ± 10.66ï¼½ U/mg prot, P < 0.05), but decreased percentage of MAS (ï¼»22.20 ± 6.07ï¼½% vs ï¼»39.30 ± 7.36ï¼½%, P < 0.05) and MDA level (ï¼»36.41 ± 4.27ï¼½ vs ï¼»54.91 ± 5.12ï¼½ nmol/mg prot, P < 0.05). The mRNA expressions of Nrf2, HO-1 and NQO-1 in the testis tissue were significantly down-regulated in the TI model controls compared with those in the normal controls (P < 0.05), and remarkably up-regulated in the CTWE treatment group in comparison with those in the TI model group (P < 0.05), while that of Caspase3 markedly increased in the TI model controls (P< 0.05) and decreased in the CTWE treatment group (P < 0.05). Histopathologically, the testis tissue of the TI model controls showed indistinct outlines from the base of the seminiferous tubule to the lumen surface, with disarranged and reduced layers of spermatogenic cells and decreased number of sperm in the seminiferous tubules, while the structure of the spermatogenic tubules recovered almost to normal in the CTWE treatment group. CONCLUSION: Cistanches tubulosa water extract can effectively inhibit cyclophosphamide-induced testis injury by enhancing the activity of antioxidant enzyme and regulating the expressions of the Nrf2 signaling pathway-related genes.