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黄连木通过 Ubc13/p53 信号通路缓解双酚 A 诱导的毒性。

Pistacia integerrima alleviated Bisphenol A induced toxicity through Ubc13/p53 signalling.

机构信息

Signal Transduction Lab, Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.

Department of Biological Sciences, National University of Medical Sciences, C/O MH, Rawalpindi, 46000, Pakistan.

出版信息

Mol Biol Rep. 2020 Sep;47(9):6545-6559. doi: 10.1007/s11033-020-05706-x. Epub 2020 Aug 8.

DOI:10.1007/s11033-020-05706-x
PMID:32770526
Abstract

Exposure to environmental toxicants such as Bisphenol A (BPA) has raised serious health issues globally particularly in developing countries. It is ubiquitously used in the manufacturing of canned food and feeding bottles. BPA generated reactive oxygen species can lead to several diseases including cardiotoxicity. However, the endpoints stimulated in BPA cardiotoxicity yet need to be investigated. The current study was aimed to investigate the underlying molecular pathways which may contribute in revealing the protective effects of Pistacia integerrima against BPA induced oxidative stress. The dose of 100 µg/kg BW of BPA, 200 mg/kg BW P. integerrima, and 4 mg/kg BW melatonin was administered to Sprague Dawley rats. Present results of western blotting and qRT-PCR showed the increased expression of p53, PUMA and Drp1, while downregulation of Ubc13 in heart tissues of BPA treated group whereas the levels were reversed upon treatment with P. integerrima. The role of BPA in heart tissue apoptosis was further confirmed by the increased level of P-p53, cytochrome C and disrupted cellular architecture whereas the P. integerrima has shown its ameliorative potential by mitigating the adverse effects of BPA. Moreover, the oxidant, antioxidant, lipid, and liver markers profile has also revealed the therapeutic potential of P. integerrima by maintaining the levels in the normal range. However, melatonin has also manifested the normalized expression of apoptotic markers, biochemical markers, and tissue architecture. Conclusively, the data suggest that P. integerrima may be a potential candidate for the treatment of BPA induced toxicity by neutralizing the oxidative stress through Ubc13/p53 pathway.

摘要

暴露于环境毒物,如双酚 A(BPA),在全球范围内引起了严重的健康问题,尤其是在发展中国家。它广泛用于罐头食品和奶瓶的制造。BPA 产生的活性氧可以导致几种疾病,包括心脏毒性。然而,BPA 心脏毒性的终点仍需进一步研究。本研究旨在探讨潜在的分子途径,这些途径可能有助于揭示开心果对 BPA 诱导的氧化应激的保护作用。BPA 的剂量为 100μg/kg BW,开心果的剂量为 200mg/kg BW,褪黑素的剂量为 4mg/kg BW,给予 Sprague Dawley 大鼠。Western blot 和 qRT-PCR 的结果显示,BPA 处理组心脏组织中 p53、PUMA 和 Drp1 的表达增加,而 Ubc13 的表达下调,而用开心果治疗后水平则逆转。BPA 对心脏组织凋亡的作用进一步通过增加 P-p53、细胞色素 C 和破坏的细胞结构水平得到证实,而开心果通过减轻 BPA 的不良反应显示出其改善潜力。此外,氧化应激、抗氧化、脂质和肝脏标志物谱也揭示了开心果的治疗潜力,通过将水平维持在正常范围内。然而,褪黑素也表现出了凋亡标志物、生化标志物和组织形态的正常表达。总之,数据表明,开心果可能是通过 Ubc13/p53 途径中和氧化应激来治疗 BPA 诱导的毒性的潜在候选药物。

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