| Summary: |
Carotenoids are fat-soluble bioactive compounds found in plants, animals and in some microorganisms, which the ingestion has been associated with the decrease of the risk of developing various chronic degenerative diseases, such as cancer, inflammation, cardiovascular disease, cataracts, macular degeneration and others [1]. One of the responsible mechanisms for reducing the risk of developing these conditions involves the reduction or inhibition of oxidation reactions by scavenging reactive oxygen (ROS) and nitrogen species (RNS) [2-5].
However, there are controversial studies indicating that supplementation with β-carotene and retinol (apocarotenoid derived from the oxidative cleavage of β-carotene after absorption) exhibit pro-oxidant effects and may be associated with the increase of the incidence of diseases, such as cancer, and also with deleterious effects on important biomolecules to physiological system [6-10]. Thus, some hypothesis have been rose to explain the pro-oxidant behaviour of carotenoids: the interference of carotenoids in metabolic processes initiated by the catabolism of retinoic acid, the high concentration of carotenoid supplementation and the high oxygen pressure present in the intervention studies (eg smoking lung in studies with lung cancer) [8, 11]; and one hypothesis not yet explored is the antioxidant/pro-oxidant behaviour and also the biological effects of carotenoid oxidation products formed after the reaction with ROS/RNS.
β-carotene is the most known and studied carotenoid in relation to the formation of carotenoid oxidation products after the reaction with ROS, and the singlet oxygen and peroxyl radical are the most studied ROS due to recognized antioxidant capacity of carotenoids in scavenging these kind of species [3, 12, 13]. Additionally, some in vitro chemical oxidation studies of β-carotene and lycopene with potassium permanganate (oxidative cleavage) and meta-chloroperbenzoic acid (epoxidation) ar  |
Summary
Carotenoids are fat-soluble bioactive compounds found in plants, animals and in some microorganisms, which the ingestion has been associated with the decrease of the risk of developing various chronic degenerative diseases, such as cancer, inflammation, cardiovascular disease, cataracts, macular degeneration and others [1]. One of the responsible mechanisms for reducing the risk of developing these conditions involves the reduction or inhibition of oxidation reactions by scavenging reactive oxygen (ROS) and nitrogen species (RNS) [2-5].
However, there are controversial studies indicating that supplementation with β-carotene and retinol (apocarotenoid derived from the oxidative cleavage of β-carotene after absorption) exhibit pro-oxidant effects and may be associated with the increase of the incidence of diseases, such as cancer, and also with deleterious effects on important biomolecules to physiological system [6-10]. Thus, some hypothesis have been rose to explain the pro-oxidant behaviour of carotenoids: the interference of carotenoids in metabolic processes initiated by the catabolism of retinoic acid, the high concentration of carotenoid supplementation and the high oxygen pressure present in the intervention studies (eg smoking lung in studies with lung cancer) [8, 11]; and one hypothesis not yet explored is the antioxidant/pro-oxidant behaviour and also the biological effects of carotenoid oxidation products formed after the reaction with ROS/RNS.
β-carotene is the most known and studied carotenoid in relation to the formation of carotenoid oxidation products after the reaction with ROS, and the singlet oxygen and peroxyl radical are the most studied ROS due to recognized antioxidant capacity of carotenoids in scavenging these kind of species [3, 12, 13]. Additionally, some in vitro chemical oxidation studies of β-carotene and lycopene with potassium permanganate (oxidative cleavage) and meta-chloroperbenzoic acid (epoxidation) are available in the literature with the aim to identify the derived oxidation products of these compounds [14, 15]. However, excepting for the case of daily supplementation with high concentration of β-carotene (in mg levels) [8-10], there is no conclusive evidence to support the possible pro-oxidant effect of carotenoids and their oxidation products. Moreover, β-carotene and lycopene are not the only carotenoids ingested during feeding, but other compounds are also often consumed, such as lutein, zeaxanthin, β-cryptoxanthin and astaxanthin; however, the study of the redox potential of such compounds and their oxidation products are neglected. Additionally, there are other ROS/RNS with high biological importance, namely hypochlorous acid (HOCl), superoxide anion radical (O2●-), nitric oxide (●NO) and peroxynitrite anion (ONOO-), whose interaction with carotenoids have not been approached in order to evaluate the reactivity of the final products.
Considering that there are many gaps and inconsistent data regarding the potential pro-oxidant effect of carotenoid oxidation products; in this project, a multidisciplinary approach which covers the study of the identification of such oxidation products, followed by the isolation (high purity) to evaluate the redox behaviour and also the biological effects in two different cellular systems: humans erythrocytes (model to study the oxidative damage in cell membranes) and human neutrophils (model to assess the inflammatory or anti-inflammatory potential).
Thus, the expected result for this project is to provide scientific support for the elucidation of a scientific controversy topic concerning the antioxidant/pro-oxidant behaviour of carotenoids in physiological systems. Furthermore, the identification of the carotenoid oxidation products represents a great advance in understanding the chemical mechanism by which carotenoids scavenge HOCl, O2●-, ●NO and ONOO- at that moment they play antioxidant action. The research group at Faculty of Pharmacy, University of Porto has developed a special interest in the antioxidant properties of carotenoids due to the stimulus created by the productive partnership [2-5, 16] with Prof. PhD. Adriana Mercadante from UNICAMP (University of Campinas, Brazil), Full Professor in Chemistry of Organic Compounds, current member of the council of the International Society of Carotenoids, and she has international recognition in the study of structural identification of carotenoids and its degradation products, as well as in the chemistry related to the antioxidant behaviour of these compounds [15-18]. For these reasons, the involved teams dominate areas and complementary knowledge, tools and methodologies needed to provide visibility, productivity and promising results for this project. |