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环磷酰胺诱导的生殖毒性:蜡菊(菊科)对雄性 Wistar 大鼠的有益作用。

Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats.

机构信息

Animal Physiology and Phytopharmacology Laboratory, University of Dschang, P.O. BOX 67, Dschang, Cameroon.

Animal Physiology and Phytopharmacology Laboratory, University of Dschang, P.O. BOX 67, Dschang, Cameroon.

出版信息

J Integr Med. 2019 Sep;17(5):366-373. doi: 10.1016/j.joim.2019.07.002. Epub 2019 Jul 17.

DOI:10.1016/j.joim.2019.07.002
PMID:31420286
Abstract

OBJECTIVE

Cyclophosphamide (CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract (AE) and methanolic extract (ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats.

METHODS

In addition to a normal control (group 1), drugs or vehicles were administered orally to seven groups (n = 5) of rats that had already received 4-weeks of pre-treatment with CP (5 mg/[kg·d], per oral administration); group 2 received CP + distilled water (10 mL/[kg·d]); group 3 received CP + 5% tween 80 (10 mL/[kg·d]); group 4 received CP + clomiphene citrate (0.25 mg/[kg·d]); groups 5 and 6 received CP + AE (50 and 100 mg/[kg·d]) and groups 7 and 8 received CP + ME (50 and 100 mg/[kg·d]). Animals were sacrificed on day 15, and body and sexual organ weights, sperm characteristics, testosterone level and testicular histology were evaluated.

RESULTS

The CP-treated group showed a significant reduction (P < 0.001) in the body and seminal vesicle weights, testosterone level, sperm count, sperm motility and sperm viability, but elevated (P < 0.001) sperm morphological abnormalities and testicular structure alterations, compared to the control group. Interestingly, these detrimental effects of CP were reversed by treatment with H. odoratissimum extracts. For instance, both extracts and all doses of H. odoratissimum significantly increased the sperm count (P < 0.001), sperm motility (AE, 50 mg/kg, P < 0.05; ME, 50 and 100 mg/kg, P < 0.05) and sperm viability (AE, 50 mg/kg, P < 0.001; ME, 50 and 100 mg/kg, P < 0.001) compared to the CP group. H. odoratissimum also improved plasmatic and intratesticular testosterone levels and prevented histological alterations of the testes.

CONCLUSION

H. odoratissimum might be considered as an alternative drug to alleviate/prevent reproductive damage in cancer patients receiving CP chemotherapy.

摘要

目的

环磷酰胺(CP)常用于治疗某些癌症,但它的临床疗效也与睾丸毒性有关。我们研究了 Helichrysum odoratissimum 的水提物(AE)和甲醇提取物(ME)在减少 CP 诱导的雄性大鼠生殖毒性中的作用。

方法

除正常对照组(第 1 组)外,已接受 4 周 CP 预处理的 7 组大鼠(n=5)经口给予药物或载体;第 2 组给予 CP+蒸馏水(10 mL/[kg·d]);第 3 组给予 CP+5%吐温 80(10 mL/[kg·d]);第 4 组给予 CP+克罗米酚(0.25 mg/[kg·d]);第 5 组和第 6 组给予 CP+AE(50 和 100 mg/[kg·d]);第 7 组和第 8 组给予 CP+ME(50 和 100 mg/[kg·d])。第 15 天处死动物,评估体重、性器官重量、精子特征、睾丸组织学和睾酮水平。

结果

与对照组相比,CP 处理组的体重和精囊重量、睾酮水平、精子计数、精子活力和精子活力显著降低(P<0.001),但精子形态异常和睾丸结构改变明显升高(P<0.001)。有趣的是,H. odoratissimum 提取物逆转了 CP 的这些有害影响。例如,两种提取物和所有剂量的 H. odoratissimum 均显著增加了精子计数(P<0.001)、精子活力(AE,50mg/kg,P<0.05;ME,50 和 100mg/kg,P<0.05)和精子活力(AE,50mg/kg,P<0.001;ME,50 和 100mg/kg,P<0.001)与 CP 组相比。H. odoratissimum 还改善了血浆和睾丸内睾酮水平,并防止了睾丸的组织学改变。

结论

H. odoratissimum 可被认为是一种替代药物,用于减轻/预防接受 CP 化疗的癌症患者的生殖损伤。

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