Protective effect of Pyripyropene A on H₂O₂-induced DNA oxidative damage in L02 cells.

IF 2.7 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2025-09-24 DOI:10.1080/15376516.2025.2561734

Lan Yang, Yewen Lin, Wenping Xu, Yang Zhang

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引用次数: 0

Abstract

Reactive oxygen species (ROS)-induced DNA oxidative damage is a significant manifestation of oxidative stress in the body and is closely associated with the onset and progression of various diseases. Although Pyripyropene A (PPPA) exhibits anti-tumor and anti-inflammatory activities, its antioxidant and protective effects against DNA oxidative injury remain unclear. In this study, using a hydrogen peroxide-induced oxidative injury model of L02 cells, it was found that PPPA could significantly reduce intracellular ROS and malondialdehyde (MDA) levels, enhance the activities of catalase (CAT) and reduced glutathione (GSH), and increase the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) clearance rate, confirming its antioxidant effect. Comet assay showed a reduction in DNA breakage, and down-regulation of phosphorylated histone (γ-H2AX) and 8-hydroxydeoxyguanosine (8-oxodG), indicating that it effectively alleviates DNA oxidative injury. Meanwhile, the upregulated expression of poly ADP-ribose polymerase (PARP) suggests that PPPA may promote repair by activating the DNA damage response (DDR). This study systematically clarify for the first time that PPPA exerts a protective effect by synergistically antioxidizing, reducing DNA injury, and potentially activating repair pathways, providing a theoretical basis for its application in neoplasm and oxidative stress-related diseases.

查看原文本刊更多论文

pyripyropena对h2o2诱导的L02细胞DNA氧化损伤的保护作用。

活性氧（Reactive oxygen species， ROS）诱导的DNA氧化损伤是机体氧化应激的重要表现，与多种疾病的发生和发展密切相关。虽然pyripyropena （PPPA）具有抗肿瘤和抗炎活性，但其抗氧化和保护DNA氧化损伤的作用尚不清楚。本研究通过过氧化氢诱导的L02细胞氧化损伤模型，发现PPPA能显著降低细胞内ROS和丙二醛（MDA）水平，增强过氧化氢酶（CAT）和还原性谷胱甘肽（GSH）活性，提高2,2-二苯基-1-picrylhydrazyl （DPPH）清除率，证实其抗氧化作用。彗星分析显示，DNA断裂减少，磷酸化组蛋白（γ-H2AX）和8-羟基脱氧鸟苷（8-oxodG）下调，表明其有效缓解了DNA氧化损伤。同时，聚adp核糖聚合酶（PARP）的表达上调表明PPPA可能通过激活DNA损伤反应（DDR）来促进修复。本研究首次系统阐明PPPA通过协同抗氧化、减少DNA损伤和潜在激活修复途径发挥保护作用，为其在肿瘤和氧化应激相关疾病中的应用提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.