Research Article Xanthine-Catechin Mixture Enhances Lithium-Induced Anti-Inflammatory Response in Activated Macrophages In Vitro Fernanda Barbisan, 1 Verônica Farina Azzolin, 1 Cibele Ferreira Teixeira, 1 Moisés Henrique Mastella, 2 Euler Esteves Ribeiro, 3 Pedro Antonio Schmidt do Prado-Lima, 4 Raquel de Souza Praia, 2 Marta Maria Medeiros Frescura Duarte, 5 and Ivana Beatrice Mânica da Cruz 1,2 1 Postgraduate Program of Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil 2 Postgraduate Program of Gerontology, Federal University of Santa Maria, Santa Maria, RS, Brazil 3 Open University of the Tird Age, State University of Amazonas, Manaus, AM, Brazil 4 Brain Institute, Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil 5 Lutheran University of Brazil, Santa Maria, RS, Brazil Correspondence should be addressed to Ivana Beatrice Mˆ anica da Cruz; ivana.ufsm@gmail.com Received 14 July 2017; Revised 19 September 2017; Accepted 11 October 2017; Published 8 November 2017 Academic Editor: Gjumrakch Aliev Copyright © 2017 Fernanda Barbisan et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Lithium (Li) is a chemical element used for treating and preventing bipolar disorder (BD) and exerts positive efects such as anti- infammatory efects as well as undesirable side efects. Tese efects of Li can be infuenced by interaction with some nutritional elements. Terefore, we investigated the potential efects of xanthine (cafeine and theobromine) and catechin molecules present in some food beverages broadly consumed worldwide, such as cofee and tea, on Li-induced anti-infammatory efects. In the present study, we concomitantly exposed RAW 264.7 macrophages to Li, isolated xanthine and catechin molecules, and a xanthine-catechin mixture (XC mixture). We evaluated the efects of these treatments on cell proliferation, cell cycle progression, oxidative and antioxidant marker expression, cytokine levels, gene expression, and GSK-3 enzyme expression. Treatment with the XC mixture potentialized Li-induced anti-infammatory efects by intensifcation of the following: GSK-3 inhibitory action, lowering efect on proinfammatory cytokines (IL-1, IL-6, and TNF), and increase in the levels of IL-10 that is an anti-infammatory cytokine. Despite the controversial nature of cafeine consumption by BD patients, these results suggested that consumption of cafeine, in low concentrations, mixed with other bioactive molecules along with Li may be safe. 1. Introduction Lithium (Li) is a chemical element that naturally occurs in soil and water (mostly at low concentrations) and enters the food chain. Low levels of Li are suggested to exert benefcial efects, and high levels of Li are suggested to exert toxic efects in living organisms [1]. Li has been used for treating psychiatric disorders for over 50 years and continues to be a frst-line drug for treating and preventing the symptoms of bipolar disorder (BD) [2]. Pharmacologically, Li exerts diferent efects, including anti-infammatory efects, on various biological and bio- chemical pathways, unlike conventional drugs that interact with specifc molecular targets. Li inhibits the expression of glycogen synthase kinase 3 (GSK3), a proinfammatory enzyme that is directly implicated in the pathogenesis of mood disorders such as BD (Luca et al. [3]). Despite its recognized efcacy, Li has a poor safety profle because of its narrow therapeutic window. Terefore, Li concentrations and clinical symptoms of patients treated with psychiatric drugs should be monitored regularly [4]. Com- mon side efects of Li include gastrointestinal disturbances such as nausea and diarrhea; excessive urination; thirst (polyuria and polydipsia); tremor, primarily of the hands; weight gain; cognitive impairment; and sexual dysfunction, Hindawi BioMed Research International Volume 2017, Article ID 4151594, 10 pages https://doi.org/10.1155/2017/4151594