Dossier: Influence of alcohol consumption and smoking habits on human healthThe role of carotenoids in the prevention of human pathologies
Introduction
Carotenoids belong to the tetraterpenes family and are represented by more than 600 known natural sructural variants. Carotenoids are synthesized in plants, fungi, bacteria and algae whereas in animals and human they are not and are incorporated from their diet. The formation of the tetraterpene skeleton (phytoene), results from a loss of a proton, generating a double bond in the center of the molecule. Carotenoids are divided in two classes, carotenes containing only carbon and hydrogen atoms and oxocarotenoids (xanthophylls) which carry at least one oxygen atom. According to the number of double bonds, several cis/trans (E/Z) configurations are possible for a given molecule. In bacteria the double bond has trans-configuration whereas in plants and fungi this double bond has the cis-configuration and an additional isomerization step is involved to change the configuration of the central double bond giving eventually lycopene.
Lycopene is an open chain hydrocarbon containing 11 conjugated and 2 non-conjugated double bonds arranged in a linear array (Fig. 1 ). During chemical reactions, light or thermoenergy, these bonds can undergo isomerization from trans to mono or poly-cis isomers and the most commonly identified are all trans, 5-cis, 9-cis, 13-cis and 15-cis isomeric forms of lycopene. α-Carotene has a β-ring at one end of the chain and an ε-type at the other. γ-Carotene, a precursor of β-carotene and δ-carotene, a precursor of α-carotene are carotenoids where only one end of the chain has become cyclized (Fig. 2 ). Xanthophylls, oxygenated, green leaf carotenoids such as zeathanthin, lutein and violaxanthin are also widely distributed (Fig. 3 ). Carotenoids are natural pigments contributing to yellow, orange (yellow and orange fruits and vegetables contain hydrocarbon carotenes with substantial levels of cryptoxanthins and xanthophylls) and red pigmentations to plant tissues (red fruits and vegetables contain mainly lycopene). The green vegetables had high contents of both xanthophylls and hydrocarbon carotenes. Lycopene is a characteristic lipophilic red pigment in ripe tomato fruit (Lycopersicon esculente; Solanaceae). Since it lacks β-ionone ring structure, it lacks provitamin A activity. The orange color of carrots (Daucus carota; Umbelliferae/Apiaceae) is caused by β-carotene, widespread in higher plants and the brilliant red pigment of pepper (Capsicum annuum; Solanaceae) is due to capsanthine. Astaxanthine, is commonly found in marine animals and is responsible for the pink/red coloration of crustaceans. Shellfish and fish such as salmon are unable to synthesize carotenoids; hence, astaxanthin is produced by modification of plant carotenoids obtained in the diet. Carotenoids function along with chlorophylls in photosynthesis and serve as important protectants for plants and algae against photooxidative damage, quenching toxic oxygen species. Some herbicides (bleaching herbicides) act by inhibiting carotenoids biosynthesis and the unprotected plant is subsequently killed by photooxidation.
In animals and human, carotenoids particularly β-carotene and lycopene, play a role in the protection against photooxidative processes by acting as singlet molecular oxygen and peroxyl radicals scavengers and can interact synergistically with other antioxidants. They have been implicated in the inhibition of cancer cells in vitro [1], [2], [3], in animal models [4], [5], [6], [7], [8] and in human, as important dietary phytonutrients having cancer preventive activity for lung, colon, breast and prostate cancer [9], [10], [11].
The A group of vitamins are important metabolites of carotenoids. Vitamin A1 (retinol) has a diterpene structure but it is derived in mammals by oxidative metabolism of tetraterpenoid, mainly β-carotene, taken in the diet. Cleavage occurs in the mucosal cells of the intestine and is catalysed by an O2-dependent dioxygenase, probably via an intermediate peroxide. Vitamin A2 (dehydroretinol) is an analog of retinol containing a cyclohexadiene ring system. Retinol and its derivatives are found only in animal products and these provide some of our dietary need (Fig. 4 ).
Section snippets
Bioavailability of carotenoids
Among the 600 known carotenoids in nature, only about 20 are found in human plasma and tissues. Lycopene is the most predominant carotenoid in human plasma and has a half life of about 2–3 days. Owing to its lipophilic nature, lycopene was found to concentrate in LDL and VLDL fractions and not in HDL fraction of the serum [29]. The strong association with plasma cholesterol is most likely due to the fact that lycopene is predominantly transported in LDL which carries the bulk of cholesterol in
The carotenoid antioxidative effects
Oxidative stress has been widely postulated to be involved in the causation and progression of several chronic diseases. ROS are generated endogenously through normal metabolic activity, life style activities, and diet. They react with critical cellular biomolecules such as lipids, proteins and DNA and initiate events that lead to increased risk of chronic disease such as cancer, cardiovascular disease, and osteoporosis. Consequently, dietary antioxidants which inactivate ROS and provide
Effect on gap junctional communication
Gap junctions are cell-to-cell channels which enable connecting cells to exchange low-molecular weight compounds like nutrients and signaling molecules [96]. One feature of carcinogenesis is the loss of gap junctional communication (GJC) [97]. Induction of intercellular communication via gap junctions can be achieved with carotenoids and retinoids and is correlated with inhibited cell growth of chemically transformed cells [98]. Non-tumorous cells communicate via GJC, whereas most tumor cells
Role of carotenoids in human health
Since carotenoids are highly hydrophobic, their interaction with ROS is expected to occur in a lipophilic environment, such as in cell membranes and lipoprotein components. The carotenoids found in cells and tissues are selectively absorbed by membranes depending on the structural carotenoid features (size, shape and polarity), as well as on membrane characteristics (composition and fluidity) [111]. These properties determine the incorporation yield and the carotenoid’s ability to fit into the
Lycopene effects in alcohol-induced liver injury
Oxidative stress has been implicated in the pathogenesis of alcohol-induced liver injury [115]. Induction of cytochrome P4502E1 (CYP2E1) by ethanol is one of the main mechanisms through which ethanol generate oxidative stress [116]. Several pathways have been shown to contribute to the pathogenesis of alcoholic liver disease [117]. One of these is the induction of CYP2E1 by ethanol with the generation of oxidative stress and lipid peroxidation upon oxidation of ethanol [118]. When rats were fed
Photoprotective potential of carotenoids
Photooxidative processes play a role in the pathobiochemistry of light exposed tissues including the eye and the skin. Age-related macular degeneration which affects the macula lutea of the retina, the area of maximal visual acuity is a major cause for irreversible blindness among the elderly in the Western world [125]. Macular pigments protect against the photooxidative processes which may be related to the antioxidant activities of the macular carotenoids and/or to their light filtering
Carotenoids and cancer
Before malignancy detection, high blood levels of insulin-like growth factor (IGF-1) predicts an increased risk of breast, prostate, colo-rectal and lung cancers [142], [143], [144], [145]. In mammary cancer cells, lycopene treatment markedly reduced IGF-I stimulation of both tyrosine phosphorylation of insulin receptor substrate and DNA binding capacity of the AP-1 transcription factor [146]. These effects were associated with an increase in membrane-associated IGF-binding proteins (IGFBPs).
Carotenoids in the prevention of cardio-vascular diseases
Coronary heart disease is the major cause of morbidity and mortality in the Western world. There is extensive evidence that oxidatively modified low-density lipoproteins (LDL) are involved in the initiation and promotion of atherosclerosis [61]. Cigarette smoking is a well-known risk factor for coronary atherosclerosis [162]. Atherogenesis may be due to foam cell production by the introduction of a source of free radicals that cause LDL oxidation [163]. Thus, protection from LDL oxidation by
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