Rutin Alleviates Oxidative Stress in Chicken Hepatocytes by Inhibiting Ribotoxic Stress Response
基本信息
- 作者：Cangning Zhang; Tao Li; Chengfeng Zhao; Liqin Zhao; Duniesky Rodriguez Acosta; Osmany Chacon Chacon; Liumei Sun; Weiguo Zhao; Liang Qu; Manman Shen
- DOI：10.3390/ani16111654
- 原文链接：https://doi.org/10.3390/ani16111654
- 数据来源：crossref:crossref-animals
- 抓取时间：2026-05-30T18:53:30+00:00
- Markdown 文件：/root/worksplace/paper-tracker/exports/obsidian/2026-05-28-rutin-alleviates-oxidative-stress-in-chicken-hepatocytes-by-inhibiting-ribotoxic-stress-response.md
摘要
Oxidative stress (OS) significantly impairs poultry production; however, the protective mechanisms of rutin in the chicken liver remain unclear. In this study, we investigated the regulatory effects of rutin on oxidative stress and lipid metabolism using H2O2-exposed primary hepatocytes derived from chicken embryos. Specifically, we focused on antioxidant indicators, the Nrf2/Keap1 signaling pathway, and the ZAKα-mediated ribotoxic stress response (RSR). Results showed that pretreatment with 800 μmol/L rutin significantly alleviated oxidative damage by increasing superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, while decreasing malondialdehyde (MDA) and reactive oxygen species (ROS) levels. This protective effect was mediated by activation of the Nrf2/Keap1 signaling pathway and its downstream effectors, HO-1 and SOD2. Concurrently, rutin suppressed lipid accumulation, as evidenced by reduced levels of triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C), along with the downregulation of SREBP1 expression. Mechanistically, we found that rutin inhibited ZAKα and its downstream signaling, the p38/JNK pathway, which is associated with RSR. Crucially, co-treatment with ZAKα overexpression significantly attenuated the protective effects of rutin on both antioxidant defense and lipid regulation, confirming that rutin functions by inhibiting ZAKα-mediated signaling to restore Nrf2 activity. Molecular docking revealed a binding energy of −8.6 kcal/mol between rutin and ZAKα, verifying that ZAKα serves as a potential target for rutin. Collectively, these findings elucidate a novel mechanism whereby rutin enhances antioxidant defense and inhibits lipid deposition via the ZAKα-p38/JNK-Nrf2 signaling pathway, providing a theoretical basis for the application of rutin as a targeted regulator in poultry health.
中文整理
基础摘要（未启用或未成功调用大模型）：Oxidative stress (OS) significantly impairs poultry production; however, the protective mechanisms of rutin in the chicken liver remain unclear. In this study, we investigated the regulatory effects of rutin on oxidative stress and lipid metabolism using H2O2-exposed primary hepatocytes derived from chicken embryos. Specifically, we focused on antioxidant indicators, the Nrf2/Keap1 signaling pathway, and the ZAKα-mediated ribotoxic stress response (RSR). Results showed that pretreatment with 800 μmol/L rutin significantly alleviated oxidative damage by increasing superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, while decreasing malondialdehyde (MDA) and reactive
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命中 行为识别 关键词：activity