Drug and Chemical Toxicology ( IF 2.1 ) Pub Date : 2020-06-15 , DOI: 10.1080/01480545.2020.1774773 Vadakkepurath Raj Athira 1 , Thimmappa Shivanandappa 1 , Hanumant Narasinhacharya Yajurvedi 1
Abstract
Although, cyclophosphamide (CP) treatment is known to cause degeneration of the ovarian follicular reserve, which may have a serious consequence of the onset of early reproductive senescence, thus far there is no experimental study either to demonstrate CP-induced early onset of reproductive senescence or its prevention. Intraperitoneal administration (ip) of CP [100 mg/kg body weight (bw)/mouse] resulted in a drastic reduction in reproductive life span as shown by the onset of reproductive senescence at a significantly early age (258 days) compared to controls (349 days), whereas treatment with the root extract of the herb Decalepis hamiltonii (DH) (200 mg/Kg bw/day for 7 days), a cocktail of anti-oxidants prior to CP administration maintained normal reproductive life span in mice. Further, the CP treated mice showed a significant increase in pre-coital interval and a significant reduction in parturition index coupled with regressive changes in the uterine endometrium, whereas DH co-treatment prevented these changes. The results for the first time, demonstrate that the ovarian toxicity of CP could be prevented by an anti-oxidant to maintain a normal reproductive life span as well as reproductive outcome using mice model.
中文翻译:
环磷酰胺,一种癌症化疗药物诱导的早期生殖衰老和生殖性能改变及其在小鼠中的预防
摘要
虽然已知环磷酰胺 (CP) 治疗会导致卵巢卵泡储备退化,这可能会导致早期生殖衰老的严重后果,但迄今为止还没有实验研究证明 CP 诱导的生殖衰老早期发生或其预防。与对照组相比,CP [100 mg/kg 体重 (bw)/小鼠] 的腹膜内给药 (ip) 导致生殖寿命急剧缩短,这从生殖衰老开始于显着早年 (258 天) 就可以看出。 349天),而用草本Decalepis hamiltonii的根提取物治疗(DH)(200 mg/Kg bw/天,持续 7 天),CP 给药前的抗氧化剂混合物可维持小鼠正常的生殖寿命。此外,CP 治疗的小鼠表现出性交前间隔显着增加和分娩指数显着降低以及子宫内膜的退化变化,而 DH 联合治疗阻止了这些变化。结果首次表明,使用小鼠模型可以通过抗氧化剂来预防CP的卵巢毒性,以维持正常的生殖寿命和生殖结果。