Antioxidant Potential of Gallic Acid Prevents Di-2-ethyhexyl Phthalate-induced Inhibition of Osteogenic Differentiation.

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current drug metabolism Pub Date : 2025-04-28 DOI:10.2174/0113892002338014250416100651

Abnosi Mohammad Hussein, Parvaz Mahrokh

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引用次数: 0

Abstract

Objective: Di-2-ethylhexylphthalate (DEHP) is utilized as a plasticizer in polyvinylchloride products (PVC). When medical devices like blood bags, tubes, and syringes are employed, DEHP leaches out of the PVC polymers and enters biological fluids through non-covalent binding. The presence of DEHP in peripheral blood leads to contamination of bone marrow. Previous research has demonstrated that this chemical induces oxidative stress, which adversely affects the viability and osteo-differentiation of bone marrow mesenchymal stem cells (BMSCs). Hence, our current study aims to utilize gallic acid (GA), a natural antioxidant, to alleviate the inhibitory effects of DEHP on BMSCs' osteogenic differentiation.

Materials and methods: In osteogenic media, BMSCs extracted from Wistar rats were treated with 0.25 μM of GA and 100 μM of DEHP individually and in combination for 20 days. Then viability, total protein, malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD), alkaline phosphatase activity, production of collagen1A1 protein as well as expression of Bmp2 and 7, Smad1, Runx2, Oc, Alp, Col-1a1 genes were investigated.

Results: The viability and differentiation ability of BMSCs was significantly (p<0.0001) decreased by DEHP, while GA significantly (P<0.0001) ameliorated the effect of DEHP. DEHP caused a significant decrease (P<0.0001) in the total protein and collagen-1A1 concentration, TAC and activity of antioxidant enzymes, but significantly (P<0.001) increased MDA level. In addition, DEHP caused a significant decrease in the expression of osteo-related genes. In the co-treatment group, GA mitigated the toxic effects of DEHP compared to the control group by inhibiting DEHP-induced oxidative stress and enhancing cell viability and osteo-differ-entiation properties.

Conclusion: These results confirm that GA reduces the negative effects of DEHP on the osteo-differentiation of BMSCs at the cellular level. However, further studies are necessary to validate these findings.

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没食子酸的抗氧化潜能阻止邻苯二甲酸二乙己酯诱导的成骨分化抑制。

目的：邻苯二甲酸二乙己酯（DEHP）用作聚氯乙烯产品（PVC）的增塑剂。当使用血袋、血管和注射器等医疗设备时，DEHP从PVC聚合物中浸出，并通过非共价结合进入生物流体。DEHP在外周血中的存在导致骨髓污染。先前的研究表明，这种化学物质诱导氧化应激，从而对骨髓间充质干细胞（BMSCs）的活力和骨分化产生不利影响。因此，本研究旨在利用天然抗氧化剂没食子酸（GA）减轻DEHP对骨髓间充质干细胞成骨分化的抑制作用。材料和方法：在成骨培养基中，提取Wistar大鼠骨髓间充质干细胞，分别用0.25 μM GA和100 μM DEHP处理，并联合处理20 d。然后检测细胞活力、总蛋白、丙二醛（MDA）、总抗氧化能力（TAC）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）、碱性磷酸酶活性、胶原1a1蛋白的生成以及Bmp2和7、Smad1、Runx2、Oc、Alp、Col-1a1基因的表达。结果：骨髓间充质干细胞的活力和分化能力显著提高(p)。结论：这些结果证实GA在细胞水平上减轻了DEHP对骨髓间充质干细胞成骨分化的负面影响。然而，需要进一步的研究来验证这些发现。

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

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.