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α-生育酚与抗坏血酸联合给药对成年大鼠三氧化二砷诱导的睾丸毒性的影响。

The effect of coadministration of α-tocopherol and ascorbic acid on arsenic trioxide-induced testicular toxicity in adult rats.

作者信息

Mukhopadhyay Prabir Kumar, Dey Avijit, Mukherjee Sanjit, Pradhan Nirmal Kumar

出版信息

J Basic Clin Physiol Pharmacol. 2013;24(4):245-53. doi: 10.1515/jbcpp-2012-0039.

Abstract

BACKGROUND

Arsenic, acting as an endocrine disruptor, causes reproductive malfunctions. Studies have been undertaken to find out whether the co-supplementation of α-tocopherol and ascorbic acid (AT-AA) could reduce the arsenic-induced testicular toxicity caused by oxidative stress and resulting DNA damage.

METHODS

Adult male Wistar rats (120±10 g) were given arsenic trioxide [3 mg/kg body weight (b.wt.) per day] for 30 consecutive days and the supplement group received α-tocopherol (400 mg/kg b.wt. per day) and ascorbic acid (200 mg/kg b.wt. per day). Reproductive functions were evaluated with respect to the histoarchitecture, gametokinetic activity, androgenic potential, glutathione-dependent antioxidant status and DNA damage of the testis.

RESULTS

Arsenic treatment caused marked reduction in the relative weight of the testis (p<0.05) but showed no effect on body weight. The number of germ cells at stage VII of the spermatogenic cycle (p<0.01), the seminiferous tubular diameter (p<0.001) and Leydig cell nuclear area (p<0.01) were significantly reduced. Notable decrease in the activities of testicular Δ5, 3β-HSD (p<0.05) and 17β-HSD (p<0.01) with a concomitant fall in serum testosterone level (p<0.01) along with significant diminution in testicular glutathione S-transferase (p<0.05) activity and reduced glutathione level (p<0.01) were observed. Significant DNA damage (p<0.001) in spermatogenic cells was also noted. All these alterations including DNA strand breakage were seen to be protected with the coadministration of AT-AA.

CONCLUSIONS

The data suggest that the protection of testicular toxicity in arsenic-exposed adult rats is possible with combined coadministration of AT-AA.

摘要

背景

砷作为一种内分泌干扰物,会导致生殖功能障碍。已经开展了多项研究,以确定α-生育酚和抗坏血酸联合补充剂(AT-AA)是否能够减轻由氧化应激和由此导致的DNA损伤所引起的砷诱导的睾丸毒性。

方法

将成年雄性Wistar大鼠(120±10克)连续30天给予三氧化二砷[3毫克/千克体重(b.wt.)/天],补充剂组则接受α-生育酚(400毫克/千克体重/天)和抗坏血酸(200毫克/千克体重/天)。从睾丸的组织结构、配子发生活动、雄激素生成潜力、谷胱甘肽依赖性抗氧化状态以及DNA损伤方面对生殖功能进行评估。

结果

砷处理导致睾丸相对重量显著降低(p<0.05),但对体重没有影响。生精周期第VII阶段的生殖细胞数量(p<0.01)、曲细精管直径(p<0.001)和睾丸间质细胞核面积(p<0.01)均显著减少。观察到睾丸Δ5, 3β-羟类固醇脱氢酶(p<0.05)和17β-羟类固醇脱氢酶(p<0.01)的活性显著降低,同时血清睾酮水平下降(p<0.01),睾丸谷胱甘肽S-转移酶活性显著降低(p<0.05),谷胱甘肽水平降低(p<0.01)。还注意到生精细胞存在显著的DNA损伤(p<0.001)。所有这些改变包括DNA链断裂在联合给予AT-AA后均得到了保护。

结论

数据表明,联合给予AT-AA有可能保护成年砷暴露大鼠的睾丸毒性。

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