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抗坏血酸补充剂可改善未成年期接触瑞舒伐他汀的雄性大鼠睾丸激素信号、精子生成和氧化应激。

Ascorbic acid supplementation ameliorates testicular hormonal signaling, sperm production and oxidative stress in male rats exposed to rosuvastatin during pre-puberty.

机构信息

Graduate Program in Cell and Structural Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, Brazil.

Department of Morphology, São Paulo State University (Unesp), Institute of Biosciences, Botucatu, Brazil.

出版信息

J Appl Toxicol. 2019 Feb;39(2):305-321. doi: 10.1002/jat.3720. Epub 2018 Sep 21.

Abstract

Dyslipidemias are occurring earlier in the population due to the augmentation of obesity. Rosuvastatin reduces cholesterol and triglycerides; however, previous studies have shown that it may affect male reproduction. Ascorbic acid (AA), an antioxidant compound, plays a protective role in the male reproductive system. This study aimed to evaluate whether pre-pubertal exposure to rosuvastatin may impair testicular structure and antioxidant status in male rats and if supplementation with AA may alleviate these damages. Male rats were randomly divided into six experimental groups (n = 10) on postnatal day (PND) 23 and received the different treatments by gavage from PND 23 to 53. The experimental groups received vehicle (saline solution 0.9%), 3 or 10 mg/kg/day of rosuvastatin diluted in saline solution 0.9%, supplementation with 150 mg/day of AA, 3 mg/kg/day of rosuvastatin in association with 150 mg/day of AA or 10 mg/kg/day of rosuvastatin associated with 150 mg/day of AA. Testicular parameters were assessed on PND 53 and 110. There were diminished androgen receptors staining in the Sertoli cells and increased germ cell death in rosuvastatin-exposed groups, in both periods. Spermatids showed lower estrogen alpha-receptors staining in the group exposed to 10 mg of statin at adulthood. There were androgen depletion and increased lipid peroxidation and catalase activity in statin-exposed groups. Rosuvastatin exposure during pre-puberty impaired testicular structure, steroid receptor distribution and increased oxidative stress; however, AA was able to ameliorate the impairment provoked by statin exposure.

摘要

由于肥胖的增加,血脂异常在人群中出现得更早。瑞舒伐他汀可降低胆固醇和甘油三酯;然而,先前的研究表明,它可能会影响男性生殖。抗坏血酸(AA)是一种抗氧化化合物,在男性生殖系统中发挥保护作用。本研究旨在评估在青春期前暴露于瑞舒伐他汀是否会损害雄性大鼠的睾丸结构和抗氧化状态,以及补充 AA 是否可以减轻这些损害。雄性大鼠在出生后第 23 天(PND)随机分为六组(n=10),并通过灌胃从 PND 23 至 53 天接受不同的处理。实验组接受载体(生理盐水 0.9%)、3 或 10mg/kg/天的瑞舒伐他汀溶于生理盐水 0.9%、150mg/天的 AA 补充剂、3mg/kg/天的瑞舒伐他汀与 150mg/天的 AA 联合使用或 10mg/kg/天的瑞舒伐他汀与 150mg/天的 AA 联合使用。在 PND 53 和 110 天评估睾丸参数。在瑞舒伐他汀暴露组中,Sertoli 细胞中的雄激素受体染色减少,生殖细胞死亡增加,在两个时期均如此。在成年期暴露于 10mg 他汀类药物的组中,精子细胞的雌激素α受体染色较低。雄激素耗竭、脂质过氧化和过氧化氢酶活性增加均见于他汀类药物暴露组。青春期前暴露于瑞舒伐他汀会损害睾丸结构、甾体受体分布并增加氧化应激;然而,AA 能够改善他汀类药物暴露引起的损害。

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