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南极磷虾肽()通过激活 Nrf2/HO-1 通路改善四氯化碳诱导的小鼠急性肝损伤。

Peptides from Antarctic krill () ameliorate acute liver injury in mice induced by carbon tetrachloride activating the Nrf2/HO-1 pathway.

机构信息

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003 Shangdong, China.

出版信息

Food Funct. 2023 Apr 24;14(8):3526-3537. doi: 10.1039/d2fo03269d.

DOI:10.1039/d2fo03269d
PMID:37014333
Abstract

This study aimed to evaluate the hepatoprotective effects of peptides from Antarctic krill (AKP) on carbon tetrachloride (CCl)-induced acute liver injury (ALI) in mice and the underlying molecular mechanisms. ICR mice were pretreated with AKP (500 mg kg, i.g.) and silybin (30 mg kg, i.g.) for 15 days before CCl (0.25 mL per kg BW, i.p.) injection. To assess hepatocellular damage and molecular indices, the serum and liver tissue were evaluated at harvest. The results showed that AKP pretreatment remarkably attenuated CCl-induced liver injury, which was identified by the decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviation of hepatocyte necrosis, and inhibition of the levels of the pro-inflammatory factors TNF-α and IL-1β compared to those for silymarin. AKP pretreatment also enhanced the redox balance by reducing the concentrations of MDA and 8-iso-PG and increasing the activities of SOD, GSH and GSH-PX in the liver of mice. In addition, AKP upregulated oxidative stress-related mRNA expressions of Nrf2, Keap1, HO-1, and NQO1 and further activated the protein expression on the Nrf2/HO-1 singling pathway. In summary, AKP might be a promising hepatoprotective nutraceutical against ALI and its underlying mechanisms are associated with activation of the Nrf2/HO-1 pathway.

摘要

本研究旨在评估南极磷虾肽(AKP)对四氯化碳(CCl)诱导的急性肝损伤(ALI)小鼠的保肝作用及其潜在的分子机制。ICR 小鼠在 CCl(0.25 mL 每 kg BW,腹腔注射)注射前用 AKP(500 mg kg,口服)和水飞蓟宾(30 mg kg,口服)预处理 15 天。为了评估肝细胞损伤和分子指标,在收获时评估血清和肝组织。结果表明,AKP 预处理可显著减轻 CCl 诱导的肝损伤,血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平降低、肝细胞坏死减轻、促炎因子 TNF-α和 IL-1β水平降低表明其效果优于水飞蓟宾。AKP 预处理还通过降低 MDA 和 8-iso-PG 的浓度以及增加 SOD、GSH 和 GSH-PX 在小鼠肝脏中的活性来增强氧化还原平衡。此外,AKP 上调了与氧化应激相关的 Nrf2、Keap1、HO-1 和 NQO1 的 mRNA 表达,并进一步激活了 Nrf2/HO-1 信号通路的蛋白表达。总之,AKP 可能是一种有前途的保肝营养保健品,可用于治疗 ALI,其潜在机制与激活 Nrf2/HO-1 通路有关。

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