Modulation activity of heat-treated and untreated lactoferrin on the TLR-4 pathway in anoxia cell model and cerebral ischemia reperfusion mouse model.
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| Abstract |
This study aimed to investigate the modulation activity of heated and nonheated lactoferrins in an inflammatory pathway in anoxia and reoxygenation cell and cerebral ischemic reperfusion mouse models. Rat pheochromocytoma 12 (PC-12) cells were subjected to oxygen and glucose deprivation in vitro to construct an anoxia and reoxygenation cell model, and Institute for Cancer Research (ICR) mice were given carotid artery "ligation-relaxation" in vivo to construct a cerebral ischemic reperfusion mouse model. The protein levels of toll-like receptor 4 (TLR-4) and downstream inflammatory proteins including nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and IL-1β were detected. Meanwhile, metabonomic detection of overall metabolites of PC-12 cells was performed to screen out the specific changed metabolite affected by lactoferrin at the condition of anoxia and reoxygenation. The results showed that lactoferrin could inhibit the TLR-4-related pathway triggered by anoxia and reoxygenation and ischemic reperfusion. A total of 41 significantly changed metabolites were identified by metabonomic analysis, and glutathione was seen as a metabolite of interest in suppressing TLR-4-related pathway in anoxia and reoxygenation cell models. However, heated lactoferrin lost the ability of attenuating the TLR-4-related pathway. The loss of modulation activity of heated lactoferrin might be due to its protein aggregation, which was evidenced by larger average particle diameter than the unheated lactoferrin. This study is the first to investigate the effect of heat treatment on the modulation activity of lactoferrin in the TLR-4-related pathway in anoxia and reoxygenation cell and cerebral ischemic reperfusion mouse models, and indicate that lactoferrin may serve as a dietary intervention for cerebral ischemia.
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| Authors | Huai-Gu Yang, Hui-Ying Li, Peng Li, Xiao-Yu Bao, Guo-Xin Huang, Lei Xing, Nan Zheng, Jia-Qi Wang |
| Journal | Journal of dairy science (J Dairy Sci) Vol. 103 Issue 2 Pg. 1151-1163 (Feb 2020) ISSN: 1525-3198 [Electronic] United States |
| PMID | 31837800 (Publication Type: Journal Article) |
| Copyright | Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved. |
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