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Anti-inflammatory and Antioxidant Effect of Poly-gallic Acid (PGAL) in an In Vitro Model of Synovitis Induced by Monosodium Urate Crystals

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Abstract

Gout is a chronic and degenerative disease that affects the joints and soft tissues because of the crystalline deposit of monosodium urate. The interaction between monosodium urate crystals (MSU) and synoviocytes generates oxidative and inflammatory states. These physiological characteristics have promoted the study of poly-gallic acid (PGAL), a poly-oxidized form of gallic acid reported to be effective in in vitro models of inflammation. The effect of PGAL in an in vitro model of oxidation and synovial inflammation induced by MSU was evaluated after 24 h of stimulation through the morphological changes, the determination of oxidative stress (OS), IL-1β, and the phagocytosis of the MSU. A 20% reduction in synovial viability and the generation of vesicles were observed when they were exposed to MSU. When PGAL was used at 100 and 200 µg/ml, cell death was reduced by 30% and 17%, respectively. PGAL both doses reduce the vesicles generated by MSU. OS generation in synoviocytes exposed to 100 µg/ml and 200 µg/ml PGAL decreased by 1.28 and 1.46 arbitrary fluorescence units (AFU), respectively, compared to the OS in synoviocytes exposed to MSU (1.9 AFU). PGAL at 200 µg/ml inhibited IL-1β by 100%, while PGAL at 100 µg/ml inhibited IL-1β by 66%. The intracellular MSU decreased in synoviocytes stimulated with 100 µg/ml PGAL. The PGAL has a cytoprotective effect against damage caused by MSU in synoviocytes and can counteract the oxidative and inflammatory response induced by the crystals probably because it exerts actions at the membrane level that prevent phagocytosis of the crystals.

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Funding

We would like to thank Consejo Nacional de Ciencia y Tecnología (CONACYT) for the funding: SEP-BASICA FSSEP02-C-2018–2 #A1-S-16109.

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YZC, RSS, and MG contributed to the conception and design, data collection, analysis, and interpretation, and writing and critical revision of the article. VML, IALJ, NMA, KFM, and JFT contributed to data analysis and interpretation as well as writing and critical revision of the article.

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Correspondence to Miquel Gimeno or Roberto Sánchez-Sánchez.

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The protocol was reviewed and accepted by the research committee of INR-LGII, number 27/20.

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Zamudio-Cuevas, Y., Martínez-López, V., Luján-Juárez, I.A. et al. Anti-inflammatory and Antioxidant Effect of Poly-gallic Acid (PGAL) in an In Vitro Model of Synovitis Induced by Monosodium Urate Crystals. Inflammation 45, 2066–2077 (2022). https://doi.org/10.1007/s10753-022-01676-3

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