Brilliant Blue Dyes in Daily Food: How Could Purinergic System Be Affected?

Hindawi Publishing Corporation International Journal of Food Science Volume 2016, Article ID 7548498, 13 pages http://dx.doi.org/10.1155/2016/7548498 Review Article Brilliant Blue Dyes in Daily Food: How Could Purinergic System Be Affected? Leonardo Gomes Braga Ferreira,1 Robson Xavier Faria,2 Natiele Carla da Silva Ferreira,3 and Rômulo José Soares-Bezerra3 1 Laboratory of Inflammation, Oswaldo Cruz Foundation, Av. Brazil, 4365 Rio de Janeiro, RJ, Brazil Laboratory of Toxoplasmosis, Oswaldo Cruz Foundation, Av. Brazil, 4365 Rio de Janeiro, RJ, Brazil 3 Laboratory of Cellular Communication, Oswaldo Cruz Foundation, Av. Brazil, 4365 Rio de Janeiro, RJ, Brazil 2 Correspondence should be addressed to Robson Xavier Faria; Received 31 May 2016; Accepted 28 August 2016 Academic Editor: Rosana G. Moreira Copyright © 2016 Leonardo Gomes Braga Ferreira et al. This 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. Dyes were first obtained from the extraction of plant sources in the Neolithic period to produce dyed clothes. At the beginning of the 19th century, synthetic dyes were produced to color clothes on a large scale. Other applications for synthetic dyes include the pharmaceutical and food industries, which are important interference factors in our lives and health. Herein, we analyzed the possible implications of some dyes that are already described as antagonists of purinergic receptors, including special Brilliant Blue G and its derivative FD&C Blue No. 1. Purinergic receptor family is widely expressed in the body and is critical to relate to much cellular homeostasis maintenance as well as inflammation and cell death. In this review, we discuss previous studies and show purinergic signaling as an important issue to be aware of in food additives development and their correlations with the physiological functions. 1. Introduction The purinergic receptor superfamily has ionotropic and metabotropic receptors. These receptors are widely expressed in the body and shows distinct pharmacological properties and activation pathways [1, 2]. The G protein-coupled P2Y receptor subtypes are activated by adenosine triphosphate (ATP), uridine triphosphate (UTP), and metabolites, such as adenosine diphosphate (ADP) and uridine diphosphate (UDP). There are eight mammalian subtypes: P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Depending on the type of G protein coupled to the P2Y receptors, its activation triggers different signaling cascades. In general, these events lead to phospholipase C recruitment, inositol 3-phosphate formation, and intracellular Ca2+ release from intracellular stores, as well as modulating adenylyl cyclase-related signaling [3, 4]. On the other hand, the mammalian ATP-gated ion channels, namely, P2X, are composed of the following 7 subtypes: P2X1R, P2X2R, P2X3R, P2X4R, P2X5R, P2X6R, and P2X7R [4]. Following their activation, the P2X receptors lead to rapid mobilization of monovalent and divalent cations, such as K+ , Na+ , and Ca2+ , which depolarize plasma membrane and trigger several intracellular events. Nevertheless, because of the lack of selective agonists, synthetic ATP analogues were designed, such as 3󸀠 -O-(4-benzoyl)benzoyl-ATP and adenosine 5󸀠 -[𝛾thio]triphosphate, for pharmacological experiments. Conversely, P2YR subtypes have distinct agonist preferences. There are receptors preferentially activated by ATP, such as P2Y11R; those preferentially activated by ADP, such as P2Y1R, P2Y12R, P2Y13R; those preferentially activated by UDP, such as P2Y6R; and those preferentially activated by UTP, such as P2Y2R and P2Y4R. Yet, antagonists development has been highly prolific. There are many categories of blockers that have been properly described and used against both P2Y and P2X receptors [1, 5–8]. It is noteworthy that many diseases display purinergic signaling involvement, in which several researchers have focused on new pharmacological strategies targeting P2 receptors [5]. Indeed, Gum and colleagues have stated in 2012 some challenges in development of orally 2 International Journal of Food Science Trypan blue Brilliant Blue G O Na+ O O− S O N N H Na+ − O O S O N O S O O + Na − N H O H O S O O− + Na O Brilliant Blue FCF Na+ − O O S O O− O S O N+ N H N N H H O O S O− Na+ N N H O S − O O Na+ Reactive blue 2 O O H H N O O S H O N H O S O O− H O N O N N N O S OH O H N Phenol red H O S O O H + N Cl H O S O O Figure 1: Structure of the dyes, which are P2 receptors antagonists. purinergic receptors specific drugs and achieving suitable bioavailability [9]. Curiously, many available P2 receptor antagonists have biological and industrial uses. Brilliant Blue G (BBG) [10], reactive Blue 2 (RB-2) [11], phenolphthalein (Phenol red) [12], and trypan blue [13], shown in Figure 1, are widely used. Among these first compounds mentioned as purinergic inhibitors, they lack pharmacological selectivity, which, in turn, might inhibit one or more subtypes of P2 receptors and unexpectedly modulate some organ/tissue functions (via P2 receptor inhibition). Nevertheless, only BBG (P2X7 antagonist) was assessed in vivo (and in humans) and it has utility in the clothing and food industries. Therefore, as P2X7 has critical roles under both physiological and pathological circumstances as inflammation, infection, and tissue injury [5], this review comes up with warnings about such compound ordinary uses and purinergic signaling. 2. Industrial Uses of Brilliant Blue G and Its Derivative The Brilliant Blue dye family has several members in which BBG and FD&C Blue No. 1 have wide uses in health sciences and industrial issues. The synthetic dye Brilliant Blue G, also known as Coomassie Brilliant Blue, was first synthesized from coal tar dye. It has a reasonable stability when exposed to light, heat, and acidic conditions, whereas it has low oxidative stability. On the other hand, FD&C Blue No. 1 (also known as the Brilliant Blue FCF or E133 in the European numbering system) (Figure 1) is one of the most common dyes used in food and cosmetic preparations and medicines. FD&C Blue No. 1 was approved in various countries to be used as a food additive in dairy products, candies, cereals, cheese, toppings, jellies, liquors, and soft drinks. This dye is also used in cosmetics such as shampoos, nail polishes, lip gloss, and lip sticks and in the textile sector [14]. The uses of this dye are justified due to its high cost-benefits as blue is not a color currently found in secretions in the body [15]. It is noteworthy that FD&C Blue No. 1 is also found in green shaded food and drinks as a mixture with yellow dyes. It has a low gastrointestinal absorption, and the amount absorbed is highly excreted by biliary vesicles and urinary routes [16]. However, FD&C Blue No. 1 utilization (...truncated)