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雨生红球藻虾青素通过 Keap1/Nrf2/HO-1 通路改善化疗药物(多柔比星)诱导的小鼠肝损伤。

Astaxanthin from Haematococcus pluvialis ameliorates the chemotherapeutic drug (doxorubicin) induced liver injury through the Keap1/Nrf2/HO-1 pathway in mice.

机构信息

Institute of Molecular Agriculture and Bioenergy, Shanxi Agricultural University, Taigu 030801, China.

出版信息

Food Funct. 2020 May 1;11(5):4659-4671. doi: 10.1039/c9fo02429h. Epub 2020 May 14.

DOI:10.1039/c9fo02429h
PMID:32405635
Abstract

The aim of this study is to probe a new function of astaxanthin (AST) from Haematococcus pluvialis on chemotherapeutic drug induced liver injury in mice. Doxorubicin-induced liver injury was treated with different doses of AST, and the body weight, food intake, urinalysis, liver function, and oxidative stress indexes were examined. The hepatocyte apoptosis level, pathological sections of liver tissue and the expression of antioxidant related genes were also determined. This study found that DOX could induce serious liver injury through cytotoxicity. AST treatment could decrease the level of liver function indexes (ALT, GOT, ALP and TBil), reduce the concentration of MDA and ROS, and increase the activities of SOD, CAT and GPX in the liver. AST could also repair the damaged hepatocyte in mice with liver injury and reduce the degree of the cellular apoptosis. In addition, AST could interfere with the expression of some related genes in the Keap1/Nrf2 signaling pathway by downregulating the expression of Keap1 and activating the transcription factor Nrf2 via enhancing the level of ERK, which upregulates downstream peroxiredoxins. The present research found and illustrated a new food function of AST, indicating that AST could be used in the therapy of chemotherapy induced side effects.

摘要

本研究旨在探讨雨生红球藻虾青素(AST)在小鼠化疗药物诱导肝损伤中的新功能。用不同剂量的 AST 处理多柔比星诱导的肝损伤,检测体重、摄食量、尿液分析、肝功能和氧化应激指标。还测定了肝细胞凋亡水平、肝组织病理切片和抗氧化相关基因的表达。本研究发现,DOX 通过细胞毒性诱导严重的肝损伤。AST 处理可降低肝功能指标(ALT、GOT、ALP 和 TBil)的水平,降低 MDA 和 ROS 的浓度,增加肝脏中 SOD、CAT 和 GPX 的活性。AST 还可以修复肝损伤小鼠受损的肝细胞,降低细胞凋亡程度。此外,AST 通过下调 Keap1 表达和通过增强 ERK 水平激活转录因子 Nrf2,干扰 Keap1/Nrf2 信号通路中的一些相关基因的表达,上调下游过氧化物酶。本研究发现并说明了 AST 的一个新的食品功能,表明 AST 可用于化疗引起的副作用的治疗。

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