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姜黄素通过调节 PINK1/Parkin 通路和保护线粒体功能减轻鸭骨骼肌砷诱导的损伤。

Curcumin alleviates arsenic-induced injury in duck skeletal muscle via regulating the PINK1/Parkin pathway and protecting mitochondrial function.

机构信息

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

出版信息

Toxicol Appl Pharmacol. 2022 Jan 1;434:115820. doi: 10.1016/j.taap.2021.115820. Epub 2021 Dec 10.

Abstract

Arsenic is a well-known environmental pollutant due to its toxicity, which can do harm to animals and human. Curcumin is a polyphenolic compound derived from turmeric, commonly accepted to have antioxidant properties. However, whether curcumin can ameliorate the damage caused by arsenic trioxide (ATO) in duck skeletal muscle remains largely unknown. Therefore, the present study aims to investigate the potential molecular mechanism of curcumin against ATO-induced skeletal muscle injury. The results showed that treating with curcumin could attenuate body weight loss induced by ATO and reduced arsenic content accumulation in the skeletal muscle of duck. Curcumin was also able to alleviated the oxidative stress triggered by ATO, which was manifested by the increase of T-AOC and SOD, and MDA decrease. Moreover, we observed that curcumin could ease mitochondrial damage and vacuolate degeneration of nucleus. Our further investigation found that ATO disrupted normal mitochondrial fission/fusion (Drp1, OPA1, Mfn1/2) and restrained mitochondrial biogenesis (PGC-1α, Nrf1/2, TFAM), while curcumin could promote mitochondrial fusion and activated PGC-1α pathway. Furthermore, curcumin was found that it could not only reduce the mRNA and protein levels of mitophagy (PINK1, Parkin, LC3, p62) and pro-apoptotic genes (p53, Bax, Caspase-3, Cytc), but also increased the levels of anti-apoptotic genes (Bcl-2). In conclusion, curcumin was able to alleviate ATO-induced skeletal muscle damage by improving mitophagy and preserving mitochondrial function, which can serve as a novel strategy to take precautions against ATO toxicity.

摘要

砷是一种众所周知的环境污染物,因其毒性而对动物和人类造成危害。姜黄素是一种从姜黄中提取的多酚化合物,通常被认为具有抗氧化特性。然而,姜黄素是否能改善三氧化二砷 (ATO) 对鸭骨骼肌造成的损伤在很大程度上尚不清楚。因此,本研究旨在探讨姜黄素对 ATO 诱导的骨骼肌损伤的潜在分子机制。结果表明,用姜黄素处理可减轻 ATO 引起的体重减轻,并减少鸭骨骼肌中砷的积累。姜黄素还能减轻 ATO 引发的氧化应激,表现为 T-AOC 和 SOD 增加,MDA 减少。此外,我们观察到姜黄素能缓解线粒体损伤和核空泡化变性。我们的进一步研究发现,ATO 破坏了正常的线粒体分裂/融合(Drp1、OPA1、Mfn1/2),并抑制了线粒体生物发生(PGC-1α、Nrf1/2、TFAM),而姜黄素能促进线粒体融合并激活 PGC-1α 通路。此外,姜黄素能降低线粒体自噬(PINK1、Parkin、LC3、p62)和促凋亡基因(p53、Bax、Caspase-3、Cytc)的 mRNA 和蛋白水平,增加抗凋亡基因(Bcl-2)的水平。总之,姜黄素通过改善线粒体自噬和维持线粒体功能来减轻 ATO 引起的骨骼肌损伤,这可以作为预防 ATO 毒性的一种新策略。

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