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硒和一种新合成的硫氰基乙酰胺可降低阿霉素对雄性大鼠的性腺毒性。

Selenium and a newly synthesized Thiocyanoacetamide reduce Doxorubicin gonadotoxicity in male rat.

作者信息

Boussada Marwa, Ali Ridha Ben, Said Azaa Ben, Bokri Khouloud, Akacha Azaiez Ben, Dziri Chedli, El May Michèle Véronique

机构信息

Histology, Embryology and Cell Biology Laboratory, Medicine School, University of Tunis El Manar, Jabbari Jebel Lakhdar Street 15, 1007 Tunis, Tunisia.

Experimental Medicine Unit, Medicine School, University of Tunis El Manar, Jabbari Jebel Lakhdar Street 15, 1007 Tunis, Tunisia.

出版信息

Biomed Pharmacother. 2017 May;89:1005-1017. doi: 10.1016/j.biopha.2017.03.002. Epub 2017 Mar 10.

Abstract

Despite its deleterious effect on healthy cells and highly regenerating cells such as spermatozoa, Doxorubicin (DOX) is still one of the most used anticancer drugs in the last decades. The present work aimed to investigate the ability of the selenium (Se) and the thiocyanoacetamide (T) to reduce DOX toxicity in gonad. Adult male rats were treated with DOX intravenously (i.v.) at 3.7mg/kg/week associated with Se intragastrically (i.g.) at 0.2mg/kg/day or with T at 10mg/kg/day i.g. After 47days of treatment, sperm quality, biochemical parameters, blood cell count and histological changes in liver, testis and epididymis were assessed. The results showed a poor sperm quality, a perturbation of ionic stability and a significant alteration of lipid metabolism and hematological parameters after the sub-chronic administration of DOX. In testis, DOX exerted serious epithelium damage and numerous seminiferous tubules did not present a normal spermatogenesis. In epididymis, epithelium was altered and mastocytes infiltrated the interstitium. DOX did not exert any significant change in liver except dilatations of sinusoid capillaries. DOX association with Se or T reduced its toxicity on some hematological and biochemical parameters. Both combined treatment improved sperm quality and partially restored spermatogenesis as well as testis and epididymis' normal aspect. These findings brought new sights regarding the effect of Se and a new derivative of T in a combined treatment with DOX on germ cells, gonad and liver. The support of these relevant outcomes with further in vitro studies is necessary to highlight the accurate process involved in Se or T protection against DOX induced damages.

摘要

尽管阿霉素(DOX)对健康细胞和高度再生细胞(如精子)有有害影响,但在过去几十年中,它仍然是最常用的抗癌药物之一。本研究旨在探讨硒(Se)和硫氰基乙酰胺(T)降低DOX对性腺毒性的能力。成年雄性大鼠静脉注射(i.v.)DOX,剂量为3.7mg/kg/周,同时胃内注射(i.g.)Se,剂量为0.2mg/kg/天,或胃内注射T,剂量为10mg/kg/天。治疗47天后,评估精子质量、生化参数、血细胞计数以及肝脏、睾丸和附睾的组织学变化。结果显示,亚慢性给予DOX后,精子质量差,离子稳定性紊乱,脂质代谢和血液学参数显著改变。在睾丸中,DOX造成严重的上皮损伤,许多生精小管未呈现正常的精子发生。在附睾中,上皮发生改变,肥大细胞浸润间质。DOX除了使窦状毛细血管扩张外,对肝脏没有产生任何显著变化。DOX与Se或T联合使用可降低其对一些血液学和生化参数的毒性。两种联合治疗均改善了精子质量,部分恢复了精子发生以及睾丸和附睾的正常外观。这些发现为Se和T的一种新衍生物与DOX联合治疗对生殖细胞、性腺和肝脏的影响带来了新的见解。需要进一步的体外研究来支持这些相关结果,以突出Se或T保护细胞免受DOX诱导损伤所涉及的精确过程。

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