The protective mechanisms of glycyrrhizic acid for deoxynivalenol-induced toxicity in rabbit corneal stroma

IF 2.7 3区 医学 Q3 TOXICOLOGY
Chunlan Liang , Xuewei Xiong , Qi Shi , Qingqing Li , Guocheng Yu , Jingxiang Zhong , Lian Liu
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Abstract

Objectives

This study aimed to investigate the effects and mechanisms of deoxynivalenol (DON) on rabbit corneal stroma cell culture and observe the protective effect of glycyrrhizic acid (GA) against DON-induced damage.

Methods

Rabbit corneal stromal cells (RCSCs) were isolated and divided into groups: control group (CON), 0.5 mmol/L GA (GA group), 400 ng/mL DON (DON group), and 0.5 mmol/L GA + 400 ng/mL DON (GAD). The effect of GA on RCSCs induced by DON was evaluated using various assays, including CCK-8 assay, Flow cytometry, qPCR, and Western blot.

Results

DON inhibited RCSCs proliferation, increased apoptosis, and raised the proportion of cells in the S and G2/M phase. It raised reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential (MMP). Additionally, DON upregulated Bax, Caspase-3, inflammatory factors (IL-1α, IL-1β, TNF-α), and matrix metalloproteinases (MMP-1/8), while downregulating tissue inhibitors of matrix metalloproteinases (TIMP-1) and type I collagen. In contrast, GA partially restored RCSCs proliferation and reduced apoptosis, inflammation, and collagen degradation.

Conclusions

DON can induce toxicity in RCSCs, promoting the expression of inflammatory factors, disrupting the balance between MMP-1/8 and TIMP-1, and promoting type I collagen degradation. Conversely, GA reduces the oxidative stress damage, cell apoptosis, and inflammatory reaction of RCSCs induced by DON, and reduces the degradation of type I collagen.

Abstract Image

甘草酸对脱氧雪腐镰刀醇致兔角膜基质毒性的保护机制。
目的:研究脱氧雪腐镰刀菌醇(DON)对兔角膜基质细胞培养的影响及其机制,并观察甘草酸(GA)对DON损伤的保护作用。方法:分离兔角膜基质细胞(RCSCs),分为对照组(CON)、0.5 mmol/L GA组(GA组)、400 ng/mL DON组(DON组)、0.5 mmol/L GA + 400 ng/mL DON (GAD)。采用CCK-8、流式细胞术、qPCR、Western blot等多种检测方法评价GA对DON诱导的RCSCs的影响。结果:DON抑制RCSCs增殖,增加凋亡,提高S期和G2/M期细胞比例。升高活性氧(ROS)水平,降低线粒体膜电位(MMP)。此外,DON上调Bax、Caspase-3、炎症因子(IL-1α、IL-1β、TNF-α)和基质金属蛋白酶(MMP-1/8),下调基质金属蛋白酶(TIMP-1)和I型胶原的组织抑制剂。相反,GA可以部分恢复RCSCs的增殖,减少细胞凋亡、炎症和胶原降解。结论:DON可诱导RCSCs毒性,促进炎症因子的表达,破坏MMP-1/8与TIMP-1之间的平衡,促进I型胶原降解。相反,GA可减轻DON诱导的RCSCs氧化应激损伤、细胞凋亡和炎症反应,减少I型胶原的降解。
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来源期刊
Toxicology in Vitro
Toxicology in Vitro 医学-毒理学
CiteScore
6.50
自引率
3.10%
发文量
181
审稿时长
65 days
期刊介绍: Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.
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