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BC99通过Nrf2/SKN-1途径和肝脏代谢调节减轻急性酒精性肝损伤诱导的氧化应激。

BC99 Attenuates Oxidative Stress Induced by Acute Alcoholic Liver Injury via Nrf2/SKN-1 Pathway and Liver Metabolism Regulation.

作者信息

Wu Ying, Li Cheng, Gao Yinyin, Zhang Jie, Dong Yao, Zhao Lina, Li Yuwan, Gu Shaobin

机构信息

College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China.

Henan Engineering Research Center of Food Microbiology, Luoyang 471000, China.

出版信息

Antioxidants (Basel). 2025 Jan 20;14(1):117. doi: 10.3390/antiox14010117.

DOI:10.3390/antiox14010117
PMID:39857451
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11760874/
Abstract

Acute alcoholic liver injury (AALI) remains a significant global health concern, primarily driven by oxidative stress. This study investigated the protective mechanisms of BC99 against alcohol-induced oxidative stress using a dual model in rats and Caenorhabditis elegans. In rats, excessive alcohol was predominantly metabolized via the CYP2E1 pathway, leading to severe oxidative stress. However, intervention with BC99 suppressed CYP2E1 expression and enhanced antioxidant enzyme activities through the Nrf2/SKN-1 pathway, thereby alleviating oxidative stress. Additionally, BC99 treatment elevated glutamate and aspartate levels while reducing glycerate and glucose, which collectively increased glutathione levels and mitigated oxidative stress triggered by glucose metabolism disorders. In C. elegans, BC99 reduced excessive ROS by upregulating /, , and their downstream antioxidant genes, consequently alleviating the biotoxicity associated with alcohol-induced oxidative damage. The protective effects of BC99 were markedly diminished in the mutant (GR2245) and mutant (CF1038), further confirming the pivotal roles of SKN-1 and DAF-16 pathways in BC99-mediated antioxidant protection. Taken together, these findings reveal that BC99 mitigates alcohol-induced oxidative stress by activating the Nrf2/SKN-1 pathway and regulating liver metabolites to eliminate excess ROS, thereby providing a theoretical basis for the application of probiotics in preventing acute alcoholic liver injury.

摘要

急性酒精性肝损伤（AALI）仍然是一个重大的全球健康问题，主要由氧化应激驱动。本研究使用大鼠和秀丽隐杆线虫的双模型研究了BC99对酒精诱导的氧化应激的保护机制。在大鼠中，过量酒精主要通过CYP2E1途径代谢，导致严重的氧化应激。然而，BC99干预通过Nrf2/SKN-1途径抑制CYP2E1表达并增强抗氧化酶活性，从而减轻氧化应激。此外，BC99处理提高了谷氨酸和天冬氨酸水平，同时降低了甘油酸和葡萄糖水平，这些共同增加了谷胱甘肽水平并减轻了由葡萄糖代谢紊乱引发的氧化应激。在秀丽隐杆线虫中，BC99通过上调/、和它们的下游抗氧化基因减少过量的活性氧，从而减轻与酒精诱导的氧化损伤相关的生物毒性。在SKN-1突变体（GR2245）和DAF-16突变体（CF1038）中，BC99的保护作用明显减弱，进一步证实了SKN-1和DAF-16途径在BC99介导的抗氧化保护中的关键作用。综上所述，这些发现表明，BC99通过激活Nrf2/SKN-1途径和调节肝脏代谢产物以消除过量的活性氧来减轻酒精诱导的氧化应激，从而为益生菌在预防急性酒精性肝损伤中的应用提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/20c0c4916a44/antioxidants-14-00117-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/b609c2af485d/antioxidants-14-00117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/a4b78fc91523/antioxidants-14-00117-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/5e4bf93b9978/antioxidants-14-00117-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/58345dd3efc7/antioxidants-14-00117-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/54b163fc47d8/antioxidants-14-00117-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/9b20a43889f6/antioxidants-14-00117-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/20047c45f48c/antioxidants-14-00117-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/20c0c4916a44/antioxidants-14-00117-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/b609c2af485d/antioxidants-14-00117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/a4b78fc91523/antioxidants-14-00117-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/5e4bf93b9978/antioxidants-14-00117-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/58345dd3efc7/antioxidants-14-00117-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/54b163fc47d8/antioxidants-14-00117-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/9b20a43889f6/antioxidants-14-00117-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/20047c45f48c/antioxidants-14-00117-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb6/11760874/20c0c4916a44/antioxidants-14-00117-g008.jpg

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2
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Nutrients. 2024 Nov 29;16(23):4142. doi: 10.3390/nu16234142.
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Glucosamine attenuates alcohol-induced acute liver injury via inhibiting oxidative stress and inflammation.
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Curr Res Food Sci. 2024 Feb 16;8:100699. doi: 10.1016/j.crfs.2024.100699. eCollection 2024.
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Hydrogen gas alleviates acute ethanol-induced hepatotoxicity in mice via modulating TLR4/9 innate immune signaling and pyroptosis.氢气通过调节 TLR4/9 先天免疫信号和细胞焦亡缓解小鼠急性乙醇诱导的肝毒性。
Int Immunopharmacol. 2024 Jan 25;127:111399. doi: 10.1016/j.intimp.2023.111399. Epub 2023 Dec 23.
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