Effects of succinates on the inflammatory response: a review

Abstract

INTRODUCTION: Endogenous succinate functions as a pro-inflammatory factor, while exogenous succinate — as an anti-inflammatory factor. The mechanisms of effect of succinates on the inflammatory response are not fully understood. OBJECTIVE: Generalization of the current scientific knowledge on the use of exogenous succinate in inhibition of the inflammatory response. MATERIALS AND METHODS: The PubMed, Web of Science, Google Scholar, Scopus, and eLibrary international databases were used to search for relevant articles. The search keywords were: “succinic acid”, “amber acid”, “inflammation”, “meglumine sodium/solution”. The search was limited to articles published between 2012 and December 2022. The inclusion criteria were: 1) research focused on the cellular energy supply in inflammation; 2) effects of succinate on the inflammatory response intensity due to changes in the cellular energy supply; 3) correlation of the cellular energy supply with clinical and laboratory inflammatory indicators when succinate-containing drugs are used; 4) original studies. RESULTS: The initial identification analysis included over 200 published studies. After the screening, 84 full-text articles meeting the selection criteria were included in the final review: 31 literature reviews, 24 of which are dedicated to the pro-inflammatory effects of endogenous succinate, and 7 — to the anti-inflammatory effect of exogenous succinate in succinate-containing agents; and 53 original scientific articles: 27 articles are dedicated to the research of molecular mechanisms of endogenous succinate, and 26 articles are dedicated to the study of the clinical use of succinate-containing drugs. CONCLUSIONS: Endogenous succinate is defined as the most important pro-inflammatory factor. Exogenous succinate has a pronounced anti-inflammatory effect mediated by normalization of the immune cell energy supply in hypoxia. No studies have been found on the differences in the mechanism of action of endogenous and exogenous succinate.