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REVIEW ARTICLE

Lycopene as an antioxidant and its medicinal uses

Sahana. K

I BDS, Saveetha Dental College, Chennai

*Corresponding Author E-mail: Sahanakriti@gmail.com

ABSTRACT:

An antioxidant molecule inhibits the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicle, which can start chain reactions. When this reaction occurs in cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents. The antioxidant effect include a considerable reactive oxygen species scavenging activity, which allows lycopene to prevent lipid per oxidation and DNA damage. It also induces enzymes of the cellular antioxidant defense systems by activating the antioxidant response element transcription system. The tetra terpene structure of lycopene with two unconjugated bonds is easily attacked by electrophilic reagents resulting in extreme poverty reactivity towards oxygen and free radicals. Lycopene is a bright red carotene and carotenoids pigment found in tomatoes, carrots, watermelons, papayas and other red fruits and vegetables. It reduces the risk of cancers of many organs, retards growth of tumors and also has a chemopreventive effect against diseases like cardiovascular disease, osteoporosis, male infertility, protection against damage caused by ionizing radiation and reduces negative effect on cancer radiotherapy.

KEY WORDS: Lycopene, antioxidant, carotenoid, oxidation.

INTRODUCTION:

Group of molecules which are highly reactive towards biomolecules and are derivatives of oxygen are called reactive oxygen species (ROS). Oxidizing agents can be those which contain free radical in an atom or molecule which contain one or more unpaired electrons and are more reactive than non-radicals. These ROS can react with lipid, proteins and nucleic acid causing oxidative stress and damage leading to pathogenesis of age related and chronic diseases [1]. Defense from the damaging effect of ROS is provided by the antioxidant which convert the oxidants into less reactive species [2] Lycopene which is an acyclic isomer of beta carotene present in red pigmented fruits like tomatoes, watermelons, pink grapes, apricots, pink guavas and papayas is a strong antioxidant that decreases free radical attack on biomolecules [3].

Received on 15.05.2015 Modified on 24.06.2015

Accepted on 20.07.2015 © RJPT All right reserved

Research J. Pharm. and Tech. 8(8): August, 2015; Page 1043-1047

DOI: 10.5958/0974-360X.2015.00178.X

It prevents generation of ROS and effectively combats oxidative damage. It doesn’t have any vitamin A activity even though it is a carotene. lycopene is an important intermediate substance in the biosynthesis of many carotenoids, including beta carotene, which is responsible for yellow, orange, or red pigmentation, photosynthesis, photo-protection and food colouring.

Lycopene – Biochemistry:

Absorption of carotenoids in human serum and tissue takes place but the intake of tomato and tomato based food products. Tomatoes contain a red pigmented carotenoid – lycopene. Lycopene is an acyclic isomer of beta- carotene. It is a highly unsaturated hydrocarbon containing 11 conjugated bonds and 2 unconjugated double bonds. It is a potent antioxidant with single- oxygen- quenching ability [4] and when compared with beta- carotene it is twice more potent and 10 times more potent than alpha- tocophenol. Its molecular weight is 536.89 and molecular formula is C40H56 with 89.45% carbon and 10.51% hydrogen. It is abundantly found in plants or autotrophic bacteria. Fruits and vegetables containing red pigments like watermelons, pink grapes, apricots, pink guavas and papayas also contains lycopene [5]. Absorption of lycopene in its natural trans form is very poor [6]. Hence it undergoes isomerization to cis form. This cis-trans isomerization can be induced through light, thermal and chemical reactions [7]. Its absorption takes place in the GI tract and transportation takes place from the intestinal mucosa through the lymphatic system [9]. Lycopene is the most predominant carotenoid in human plasma, adrenal gland, testes, liver and prostrate [8]. It does not get involved in the synthesis mechanism of vitamin A when compared with beta- carotene and alpha- tocophenol, as it lacks beta-ionone ring structure [5]. Due to its high lipophilic nature it is commonly located within the cell membrane and other lipid components. Lycopene is insoluble in water, and can be dissolved only in organic solvents and oils. Due to its non polarity it stains porous materials easily and during oxidation, it eliminates chromophore. In plants and microorganisms it serves as an accessory light gathering pigment and provides protection against the toxic effect of oxygen and light [9].

Structure of LYCOPENE

Lycopene- Antioxidant:

Lycopene has an extensive ability to scavenge free radicals in cell culture and in animal models [10]. By trapping the ROS, OH, NO2, it leads to the oxidative breakdown of the lycopene molecule that protects against in vivo oxidation of lipids, proteins and DNA [11]. It enhances cellular antioxidant defense system by regenerating the non enzymatic antioxidants for further action [12]. In a lipophilic environment it has maximum scavenging effect on ROS and prevents its generation. In in vitro conitions lycopene can inhibit oxidation of LDL [13]. In vitro evidence indicates that lycopene reduces cellular proliferation which are potent mitogens in various cancer cell lines [14]. Its inhibitory action on cell cycle progresses from the Go/G1 to S phase [9]. Activation of phase II detoxifying enzymes to modulate cell cycle and induction of apoptosis on cancer cells at the transcriptional level [12]. Increased time of tumor development and survival time was observed with pretreatment of lycopene. It was noted that lycopene had the capacity to inhibit breast cancer cell proliferation and, endometrial, lung cancer cell growth, arrest the cell cycle at different phases, and apoptosis in cell cultures. Protection to the intestinal toxicity is done by reducing lipid peroxidation and increased antioxidant enzyme activity. By its antioxidative property it gives protection against toxicity caused by chemotherapeutic drugs that also have cytotoxic effect similar to radiation [15]. There is a strong protection provided against DNA based oxidative damage by neutralizing ROS and reducing susceptibility of lymphocytic DNA to the same based on antioxidative status of lycopene [16]. Its effect can be seen on DNA oxidative damage which is either directly induced with the help of hydrogen peroxide H2O2 or indirectly by n-nitrosodiethylamine (DEN) on models used for identifying anti-mutagens. It was shown that it prevented DEN- induced neoplasia as it prevented primary damage of DNA due to the exposure of DEN and inhibits mutagenic and genotoxic effects due to exposure of H2O2 [12]. It decreases benign prostate hyperplasia by increasing the apoptic cell death [17]. Anti-proliferative and pro-apoptotic activity of the lycopene has been observed in malignant T-lymphoblast cells. Exhibiton of anti-metastic activity by the expression of metastasis suppressor gene in a hepatocarcinoma cell line. Its action is via the mevalonte pathways [12]. It also acts as a hypocholesterolenic agent by inhibiting HMG-CoA reductase pathway [18]. Gap junctions are useful for the communication between the neighbouring cells and are formed by connexin proteins. This communication are very important for the cell growth and loss of the gap junction communication leads to carcinogenesis. Evidences prove that this communication is chemically restored by lycopene and inhibits carcinogenesis [12].

Figure 1. Schematic overview of the anti-oxidant, anti-proliferative and anti-metastatic activities of lycopene and its cellular targets as well as signaling pathways affected by this compound.

Figure 2: oxidative stress

Figure 3: antioxidative pathways

Figure4: action on DNA

Figure 5: Cellular damage.

Lycopene- Medicinal Uses:

Lycopene gave protection against myocardial infarction risk in non-smokers [19] and also with a higher plasma concentration it was associated to reduce the risk of cardio-vascular disease in women [20]. Hypothesis of lycopene improving endothelial fuction in patiets with preexisting cardio-vascular disease [21]. By treating the cardio-vascular patients with lycopene, reduction of blood pressure and improvement in Ach responses could be observed [21]. Lower plasma concentrations were linked with increase in the risk of atherosclerotic lesions. Studies show that there is an extensive impact on the male infertility. Impotent males genetically produce high levels of free radicals. By consuming 8mg/day of lycopene supplements it was shown that in 50 volunteers with low sperm count, 70% showed improved sperm count, 60% showed functional sperm concentrations, 54% showed improved sperm motility, 46% had improved sperm motility index, and 38% had improved sperm morphology [22]. Dietary intake of carotenoids provide protection from UV-induced erythema in humans [23]. According to the results of author [24] it is shown that lycopene provides protection against methylmercury (MeHG) which is a neurotoxin and also plays a role in preventing mitochondrial dysfunction. Serum lycopene level showed inverse relation with the risk of cervical intraepithelial neoplasia [25] as well as bladder cancer [26]. Low lycopene concentrations in the skin is said to provide protection against UV light stress but at higher concentrations it showed pro-oxidative effect [12]. Lycopene is said to show some beneficial effects in the treatment of oral diseases like oral cancer and precancerous lesions [9]. Oral submucous fibrosis (OSMF) is a premalignant condition characterized by progressive fibrosis of the oral mucosa [21]. The curative effect of lycopene which is due to inhibition of abnormal fibroblasts, regulates the lymphocyte resistance to stress and suppression of inflammatory response. Leukoplakia is is the most common precancerous lesion in the oral cavity with a recognizable risk for malignant transformation. Tobacco usage generates increased reactive free radicals and active oxygen species, which mediate phenotypic and genotypic alterations and lead mutations to carcinogenesis. The serum levels of lycopene and B carotene among men with oral leukoplakia were significantly lower than those of controls. Tumor suppressor gene is p53, and mutations of this gene have been observed in various sites of premalignant leukoplakia and carcinoma in the same oral cavity. A reduction in tumor suppressor activity by the gene and the development of mutations in p53 are associated with smoking and an increased risk for oral carcinoma development. Lycopene has been reported to increase p53 protein levels in cancer cells [21].

Figure 6: Free radical oxidative stress

LYCOPENE- ANIMAL TESTING:

Over the period of time there has been a lot of animal models used to analyse the absorption, tissue distribution and effect of lycopene. Concentration of lycopene is observed highest in liver,spleen and prostrate and lowest in the brain of rats in a demonstration by Jain et al.[27]. To enhance the immune response in mice, increase in T helper cells and normalizing intrathymic T cell differentiation caused by tumor genesis was observed [28]. Small doses of lycopene reduced N-methylnitrosourea (MNU) induced development of aberrant crypt foci in the Sprague-Dawley rats was seen by the author [29]. In vitro study of bone marrow prepared from rat femurs demonstrated that in the presence or absence of parathyroid hormone (PTH) lycopene inhibited osteoclastc activity of mineral resorption and formation of tartrate resistant acid phosphatase (TRAP) [30]. Laboratory demonstrations of protection against azoxymethane (AOM) induced by colonic preneoplastic lesions was noted [26]. Gluthatione oxidation was seen in adult rats due to its effect on Sertoli cells [31]. The expression of NQO1 in rats which increased mRNA and protein levels was seen due to the administration of lycopene. This subsequently was able to improve nephrotoxic phenotype which occurred due to chemotherapeutic treatment for solid tumors [12].

CONCLUSION:

Lycopene being an very effective and strong antioxidant helps not only in free radical scavenging but also plays a major role in reducing the risk of cancers of various organs. The availability of it is abundant in nature and hence the dietary supplementation of it is vast. Its influence can be observed even over other diseases such as the cardiovascular disease, osteoporosis male infertility, mitochondrial dysfunction. At low concentrations it even provides protection against UV induced erythema. By its supplementation for cancer radiotherapy, the side effects can be reduced due the chemopreventive property of it. There were a lot of trails done on the effect of lycopene on various conditions stimulated in the animal. The restoration of gap junction communication helps in the prevention of carcinogenesis. Its anti-inflammatory property also remarkably constitutes to the anti- cancer potential and age-related muscular degeneration.

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