Role of Antioxidants on Cancer and Neurodegenerative Disorders
Department of Pharmacy, SSJ College of Pharmacy, Hyderabad, Telangana, India
- *Corresponding Author:
- Prashanthi G
Department of Pharmacy
SSJ College of Pharmacy, Vattinagulapally
Rajendranagar Mandal, Hyderabad, Telangana 500075, India.E-mail: email@example.com
Received date 02/08/2016; Accepted date 05/08/2016; Published date 12/08/2016
Visit for more related articles at Research & Reviews: Journal of Medical and Health Sciences
ABSTRACT Antioxidants are the substances which protects cells from damage caused by unstable molecules known as free radicals. Free radical damage may lead to cancer and many neurodegenerative disorders. Reactive oxygen species (ROS) over production will results in oxidative stress which can leads to neuronal damage and results in cancer and Neurodegenerative. An antioxidant defence mechanism involves removal of this reactive oxygen, nitrogen species and their precursors thereby inhibit formation of ROS. Scientific research confirms that free radicals have a major role in the development of cancer, heart disease, cataracts, aging and impairment of the immune system. Nutritional antioxidants might exert some protective activity on Alzimers Disease, Parkinson Disease. This review explains that how might antioxidants help in preventing cancer along with prospective study of antioxidants their mechanism and role in cancer therapy and the biochemical process by which antioxidants can prevent neuronal death occurring in neurodegenerative disorders.
Oxidation, Free radical, Oxidative stress, Reactive oxygen species, Antioxidants, Cancer, Neurodegenerative disorders
An antioxidant is any substance which is capable of preventing the oxidation of other molecule [1-3]. In biological system they protect cells from damage that is caused by unstable molecules known as free radicals [4-6]. Antioxidants interrupt the chain reactions by removing intermediates of free radical, and inhibit other oxidation reactions by being oxidizing themselves. They help in preventing the growth of many chronic diseases. Antioxidants are emerging as prophylactic and therapeutic agents [7-10].
Antioxidants have natural activity of preventing neuronal loss and damage caused due to oxidative stress. Many antioxidants have been observed to cross the blood-brain-barrier (BBB) and have neuroprotective effect in humans as well as in animal models. But the main drawback of antioxidants is their low biological half-life and low bioavailability at the sites reactive oxygen and nitrogen species generation [11-14]. Antioxidants are the substances whose presence in low concentrations inhibits the rate of oxidation significantly.
A process called oxidation causes damage of important molecules in the body and can result in harmful processes like neuronal damage and carcinogenesis [15-18]. Oxidation is a natural process that occurs any time a when substance combines with oxygen. Antioxidants are chemicals that block this process. Scientific research now confirms that free radicals results in the development of cancer, heart disease, cataracts and impairment of the immune system. The use of antioxidants as an adjunct alternative cancer therapy is an area of intense research [19-21].
Cancer is characterized by a population of cells that grow and divide without respect to normal limits they invade and destroy adjacent tissues and have ability to spread to distant anatomic sites through a process called metastasis. Cancer may affect people of all ages. Cancer causes about 13% of all deaths. Many forms of cancer are thought to be the results between free radicals and DNA which leads to adverse effects on the cell cycle and thereby leading to malignancy [22-27].
Antioxidants in the appropriate doses showed that they had relatively good impact in making the tumors more responsive towards the chemotherapy and radiological therapy. They have the ability to inhibit the growth of tumor selectively without affecting the process of normal cells [28-32]. Hence antioxidants have the ability to protect against the toxicity caused due to chemotherapy by inhibiting cell proliferation also antioxidants are proven to have a beneficial role in reducing extraneous oxidative damage, thereby reducing the problems involved in production of ROS and neurodegenerative disorders [33-38].
Effects Of Antioxidants On Free Radicals
A free radical is any chemical substance that has one or more unpaired electrons. Unpaired electrons alter chemical reactivity of an atom or molecule and making it more reactive than the resulting non radical because they act as electron acceptors and essentially accepts electrons from other molecules [39-44]. This loss of electrons is called oxidation, and free radicals are referred to as oxidizing agents because they allow other molecules to donate their electrons (Figure 1).
Figure 1: Mechanism of action of antioxidants.
We are exposed to free radicals formed by electromagnetic radiation from both the environment, and man-created by internal biological metabolism. The most common cellular free radicals are hydroxyl radical (OH•), nitric oxide (NO•) and superoxide radical (O2•) [45-48].
Effects Of Antioxidants On Free Radicals
Natural dietary antioxidants are Vitamin A, C, and E, carotenoids, flavonoids, and polyphenols. Ascorbate is well distributed and has good bioavailability; tocopherol incorporates into lipoproteins in liver. Tocopherol is an essential chain-breaking antioxidant that inhibits lipid peroxidation [49-53]. Ascorbate plays vital role in scavenging many reactive species like O2•−, OH • and lipid hydro peroxides and can prevents catecholamine from formation of ROS. Carotenoids can help in scavenging ROS and Free radically in a very potential manner, but there is still little evidence that they contribute significantly to the antioxidant defence system in the nervous system [54-60].
Flavonoids can prevent injury caused by ROS in many ways. One is the scavenging of free radicals directly. Flavonoids get oxidized by free radicals and gives rise to a stable unreactive free radical as shown in below equation [61-63].
Flavonoids (OH) + R• → Flavonoids (O•) +RH
There are many useful health benefits of tea because of its antioxidant effects on ROS, Green tea especially showed patterns of tumour regression. Red wine also contains an antioxidant resveratrol which helps in inhibiting progression of cancer [64-66]. The antioxidant treatment will help in reducing the serum levels of TNF and IL-6 which are triggering agents of cancer. Vitamin E reduces the growth of breast and colorectal cancer cells by programmed cell death (apoptosis) [67-68]. Antioxidants are available abundantly in vegetables and fruits, also in other foods like nuts, and some- grains, meats, fish and poultry [69-72].
Some of the important antioxidants used in cancer and neurodegenerative disorders along with doses are list below:
• Beta-carotene dose: 25,000 to 100,000 IU/D
• Vitamin C dose: 3-10 g/D
• Vitamin E
• Selenium dose: 100-200 mg/D
• Lipoic acid dose: 500-1000 mg/D
• Bioflavanoides: Flavonols, Flavones, Catechins (Tea), Proanthocyanidins (Cherries)
Conclusion & Future Aspects
The study of antioxidants use in cancer treatment is a rapidly evolving area. The importance of antioxidants is underlined by a recent study that estimates 23% of cancer patients take antioxidants and there is a possibility that diets that are rich in antioxidants can reduce the incidence of cancer [73-80]. Potential antioxidant therapy involves natural antioxidant enzymes where antioxidants use may be beneficial in preventing the incidents of chronic processes such as carcinogenesis and atherosclerosis. Further controlled clinical trials of antioxidants are required to establish their efficacy [81-88]. Hence these studies and review show that a there will be gradual reduction in adverse effects caused due to chemotherapy when done along with antioxidants therapy. Since Oxidative Stress has been considered as main reason of neurological, especially neurodegenerative diseases and carcinogenesis [89-93]. Antioxidants have been experimented and trails went on for their effective use as therapeutic agents. Most of the papers hereby reviewed and checked the potency and efficiency of antioxidants in the treating neurodegenerative diseases and cancer therapy [94-100].
- Bhattacharya M and Chakraborty S. Free radicals and naturally occurring antioxidants. RROIJ. 2015.
- Neeti Sharma. Free radicals, antioxidants and disease. Biol Med. 2014;6:214.
- Butnariu M. Action and protection mechanisms of free radicals. J Pharmacogenomics Pharmacoproteomics. 2012;3:e129.
- Charushila YK and Subodhini AA. Evaluation of serum antioxidants during adjuvant chemotherapy of breast cancer- a prospective observational study. Biochem Anal Biochem. 2015;4:171.
- Panja S, et al. Antioxidants from indegenous medicinal plants inhibit proliferation of ascitic cancer cells. J Cancer SciTher. 2014.
- Shrivastava SR, et al. Advocating use of antioxidants in ensuring optimal health. J Food NutrDisor. 2013;2:121.
- Ghareeb DA and Sarhan EME. Role of oxidative stress in male fertility and idiopathic infertility:causes and treatment. J Diagn Tech Biomed Anal. 2014;2:107.
- Naspolini NF, et al. Effects of calorie restriction and soybean and olive oils on oxidative stress in obese. J Food NutrDisor. 2015;4:183.
- Shetty AA, et al. Vegetables as Sources of antioxidants. J Food NutrDisor. 2013;2:104.
- Aljerian K and Haffor A. Effects of hyperoxia exposure on free radicals accumulation in relation to ultrastructural pathological changes of diaphragm. J ClinExpPathol. 2015;5:247.
- Sinha BK. Roles of free radicals in the toxicity of environmental pollutants and toxicants. J Clinic Toxicol. 2013;S13:e001.
- Ramos P, et al. Free radicals in the thermally sterilized aminoglycoside antibiotics. Pharmaceut Anal Acta. 2012;3:193.
- Butnariu M and Samfira I. Free radicals and oxidative stress. J BioequivAvailab. 2012;4:4-6.
- Rathod GB, et al. Hazards of free radicals in various aspects of health – a review. J Forensic ToxicolPharmacol. 2014;3:119.
- Akintunde JK, et al. Sub-chronic treatment of sildernafil citrate (viagra) on some enzymatic and non-enzymatic antioxidants in testes and brain of male rats. J Pharm Drug Deliv Res. 2012;1:105.
- Clifford T, et al. The influence of different sources of polyphenols on sub-maximal cycling and time trial performance. 2013;2:130.
- Skenderi KP, et al. Total antioxidant capacity and phenolic compounds of selected vinegars in the greek market. J Food NutrDisor. 2013;2:112.
- Mohamed EB, et al. Immunomodulatory and antioxidant protective effect of zingiberofficinale, in lead intoxicated rat. Prensa Med Argent. 2015;101:152.
- Shatrova AN, et al. Antioxidant-dependent prevention of h2o2-induced premature senescence in human endometrial stem cells. Cell Biol:ResTher. 2015;4:118.
- Shetty AA, et al. Vegetables as sources of antioxidants. 2013.
- Zidan NS, et al. The protective effect of a novel coumarinic derivative on streptozotocin induced diabetic rats. J Food NutrDisor. 2016;5:195.
- Mishra P and Prasad SM. Mounting insights over human wellness by utilizing plant’s primed defense against precise/mild oxidative stress. J Plant PhysiolPathol. 2016;4:102.
- Mohapatra S and Mittra B. Induction of glutathione, ascorbate and associated enzymes by a low dose cdcl2 pre-treatment alleviate fusarium induced oxidative stress in wheat. J Plant PhysiolPathol. 2016;4:141.
- Yang S, et al. Physical activity and oxidative stress biomarkers in generally healthy women. J Community Med Health Educ. 2015;5:377.
- Jagetia GC and MallikarjunaRao KVN. Hesperidin, a citrus bioflavonoid reduces the oxidative stress in the skin of mouse exposed to partial body γ-radiation.Transcriptomics. 2015;3:111.
- Gupta DK, et al. Moderate uranium disturbs the nutritional status and induces oxidative stress in pisumsativum l. J Plant PhysiolPathol. 2016;4:142.
- Kishida S, et al. Short-term treatment with an angiotensin ii receptor blocker prevents necrotic core formation by inhibiting oxidative stress-mediated apoptosis in macrophages. J Cardiovasc Res. 2016;5:252.
- Pokorný J and Pokorný J. Biophysical pathology in cancer transformation. J ClinExpOncol. 2013;S1:003.
- Djamgoz MB. Biophysics of cancer:cellular excitability (“celex”) hypothesis of metastasis. J ClinExpOncol. 2014;S1:005.
- Al-Amoudi SM. Cancer diagnosis:who has the right to know? J Womens Health, Issues Care. 2013;2:108.
- Mirhafez SR, et al. Increased pro-oxidant–antioxidant balance in patients with diabetes mellitus. Int J Cardiovasc Res. 2015;4:207.
- Guest TC and Rashid S. Anticancer laccases:a review. J ClinExpOncol. 2016;5:153.
- Patel TN, et al. Telomeres in cancer:length, positioning and epigenetics. J Genet Disor Genet Rep. 2016;5:1.
- ElShebiney SA, et al. Cannabis resin extract in parkinson’sdisease:behavioral, neurochemical, and histological evaluation. Cell Biol:ResTher. 2014;3:112.
- Lit KW, et al. Effects of acute cool water immersion on time trial performance and exercised-induced oxidative stress among endurance cyclists in the heat. J Athl Enhancement. 2014;3:163.
- Karabulut AB, et al. Nutri-protection and mediterraneandiet:bitter apricot kernel and amygdalin treatment effects on a battery of oxidative stress and apoptosis biomarkers. J Plant PhysiolPathol. 2014;2:130.
- Sharma S, et al. Ascorbic acid reduces the phytotoxic effects of selenium on rice (oryza sativa L.) by up-regulation of antioxidative and metal-tolerance mechanisms. J Plant PhysiolPathol. 2014;128.
- Srivastava S and Sharma YK Altered growth, photosynthetic machinery and induced oxidative stress in spinach in response to arsenic stress. J Plant PhysiolPathol. 2013;1:113.
- Bonucci M. Integrated cancer therapy:treat the person to cure the cancer. International J Inflam Cancer IntegTherpy. 2016;3:e101.
- Fernández A. Anticancer therapy based on suppression of pathways recruited to cope with metabolic stress. Metabolomics. 2016;6:e144.
- Cohen EP, et al. Evaluation of genomic evidence for oxidative stress in experimental radiation nephropathy. J Genet Disor Genet Rep. 2013;2:101.
- Sinha P, et al. Oxidative stress responsive enzymes and non-enzymatic components in response to excess cadmium in pigeon pea (cajanuscajan mill) cv. upas. J Plant PhysiolPathol. 2013;1:112.
- Jascolka TL, et al. Kefir supplementation improves lipid profile and oxidative stress but does not reduce atherosclerotic lesion in apoe deficient mice. J Food NutrDisor. 2013;2:113.
- Feillet-Coudray C, et al. Xanthine oxidase is variably involved in nutritional and physio-pathologic oxidative stress situations. J PhysiobiochemMetab. 2013;2:104.
- Lawania RD and Mishra A. Anticancer potential of plants and natural products:a review. J Pharmacol Biomed Anal. 2013;1:103.
- Fahim GG, et al. Deferiprone as a potential treatment for neurodegeneration with brain iron accumulation. J Forensic ToxicolPharmacol. 2015;4:138.
- Ma L, et al. Silver sulfide nanoparticles as photothermal transducing agents for cancer treatment. J NanomaterMolNanotechnol. 2016;5:182.
- Coyne CP, et al.Gemcitabine-(c4-amide)-[anti-her2/neu] anti-neoplastic cytotoxicity in dual combination with mebendazole against chemotherapeutic-resistant mammary adenocarcinoma. J ClinExpOncol. 2013;2:109.
- Daniluk U. Probiotics, the new approach for cancer prevention and/or potentialization of anti-cancer treatment? J ClinExpOncol. 2012;1:105.
- Amanullah M, et al. Safety aspects in treatment of cancer by carbamate insecticides as measured by osmotic fragility of erythrocytes. J ClinExpOncol. 2012;2:104.
- Norollahi SE, et al. The role of micrornas in cancer progression. J ClinExpOncol. 2016;5:155.
- Mendes F, et al. Radiotherapy effects on immune system of patients with solid and hematopoietic tumors. Cell Biol:Res Ther. 2016;5:124.
- Oleksyszyn J. Spontaneous regression of cancer, an ever actual inspiration for the new cancer treatment. Cell Biol:ResTher. 2016;5:113.
- Sköld MK, et al. Spinal intraduralextramedullary prostate cancer metastasis - report of two patients and review of the literature. J Spine Neurosurg. 2016;5:220.
- Lydia J, Sudarsanam D. Anticarcinogenic effects of selected alkaloids identified from cyperusrotundus:an in silico perspective. J ApplBioinformComput Biol. 2016;5:122.
- Del Follo-Martinez A, et al. Polyphenolics from black spanish red wine (vitis ‘aestivalis’) have cytotoxic activity in colon cancer cells and repress pro-oncogenic microrna-27a. J Food NutrDisor. 2015;4:169.
- Goodman BA. Can coffee ameliorate the cancer risks associated with low-moderate alcohol consumption in men? J Food NutrDisord. 2014;3:159.
- Çetin B, et al. Peroxidation products and antioxidant enzyme activities in multinodular goiter and papillary thyroid cancer patients. J ClinExpOncol. 2014;3:127.
- de LeBlanc. The administration of probiotics and fermented products containing lactic acid bacteria exert beneficial effects against intestinal and non-intestinal cancers. J Food NutrDisor. 2014; S1-005.
- Albrecht AM, et al. Combinational treatment for pancreatic cancer:where are we standing? J ClinExpOncol. 2012;1:e103.
- Yoshihara S, et al. Laryngeal cancer in a patient with amyotrophic lateral sclerosis. 2014;3:154.
- Menaa F, et al. Dietary intake of (-)-epigallocatechin-3-gallate against aging and cancers:nanoencapsulation of multi-rings still requires new rounds! J NanomaterMolNanotechnol. 2013;2:131.
- Omabe M, et al. Metabolic basis of treatment failures; autophagy and malignant cancer progression. J ClinExpOncol. 2013; 2:111.
- Vieira A. A perspective on nutrition and cancer. J Food NutrDisor. 2012;1:e108.
- Gerber LE. Physiobiochemical significance of vitamin e and other tocopherols in the U.S.diet:cancer promoters or preventers? J PhysiobiochemMetab. 2012;1:e101.
- Lucas A. Atherosclerosis, cancer, wound healing, and inflammation - shared or parallel evolution. Int J Cardiovasc Res. 2012;1:e101.
- Azza AA, et al. The potential effect of caffeine and nicotine co-administration against aluminuminducedalzheimer’s disease in rats. J Alzheimers Dis Parkinsonism. 2016;6:236.
- Manna E and Maiti S. Cardio-protecting effect of natural bioactive compound (polyphenol) by inhibiting ldl oxidation with the scavenging of reactive oxygen species (ros). J ClinExpCardiolog. 2016;7:453.
- Nwozo SO, et al. Vitamin B and antioxidants in relation to treatment duration in cervical cancer patients in ibadan. Intern Med. 2013;3:127.
- Shing WL. Colourful antioxidants for environmental toxicity assessment. J Biomol Res Ther. 2013;2:e114.
- Aliev G, et al. Mitochondria specific antioxidants and their derivatives in the context of the drug development for neurodegeneration and cancer. Drug Des. 2013;2:103.
- Goh J, et al. Are exercise and mitochondrial antioxidants compatible in the treatment of invasive breast cancer? Bioenerg Open Access. 2012;1:101.
- efferth t and shan l. natural products for cancer therapy – is economic success reachable?. Med Aromat Plants. 2016;5:e174.
- Udugamasooriya G. Peptoids:an emerging class of peptidomimetics for cancer therapy and diagnostics. J Biomol Res Ther. 2013;3:e121.
- Rodríguez ML, et al. Natural polyphenols and apoptosis induction in cancer therapy. J CarcinogeneMutagene. 2013;S6:004.
- Bagchi A, et al. Tea polyphenolics and their effect on neurodegenerative disorders- a review. Research &Reviews:Journal of Medicinal & Organic Chemistry. 2015.
- Machado S. Transcranial direct current stimulation for neurodegenerative disorders. Int J Neurorehabilitation. 2016;3:e118.
- Rao G, et al. Ubiquitin-proteasome system in neurodegenerative disorders. J Drug MetabToxicol. 2015;6:187.
- Bachurin S. Contemporary approaches for pharmacological intervention of abundant neurodegenerative disorders. J NanomedineBiotherapeuticDiscov. 2015;5:e137.
- Luo JJ and Dun NJ. Neurodegenerative disorders and prionopathies. J NeurolNeurophysiol. 2013;4:e113.
- Lyubchenko YL. Nanoimaging for molecular pharmaceutics of alzheimer’s and other neurodegenerative disorders. J Mol Pharm Org Process Res. 2013;1:e107.
- Yadav R, et al. Rise and fall of reactive oxygen species (ros):implications in aging and neurodegenerative disorders. Cell Dev Biol. 2013;2:e122.
- Tsamopoulos NG, et al. Venous neurovascular pathways to neuroinflammation in neurodegenerative disorders. Microinflammation. 2014;1:112.
- Surajit S. Protein aggregation in neurodegenerative disorders:a cause or consequence? Adv Tech Biol Med. 2014;2:e105.
- Archer T. Amelioration of symptoms and biomarkers of alzheimers disease by physical exercise. Open access. 2016;2:e105.
- Woods JJ, et al. Cigarette smoking:a causal factor for alzheimers disease? JGerontolGeriatr Res. 2016;5:286.
- Allen HB, Morales D, Jones K, Joshi S (2016) Alzheimer’s disease:a novel hypothesis integrating spirochetes, biofilm, and the immune system. J Neuroinfect Dis 7:200.
- Juma KK (2015) A current understanding of alzheimer’s disease and the prospects of phytopharmacological intervention as a management strategy. J NeurolDisord 3:244.
- Abd El-Rahman HSM. The effect of olive leaf extract and α-tocopherol on nephroprotective activity in rats. J Nutr Food Sci. 2016;6:479.
- Rosa LS, et al. Anticancer properties of phenolic acids in colon cancer – a review. J Nutr Food Sci. 2016;6:468.
- Lee SJ. A different role of metallothionein-3 (mt3) in oxidative stress and neurodegeneration of brain. J Neuroinfect Dis. 2016;7:221.
- Banerjee S, et al. Drug metabolism and oxidative stress:cellular mechanism and new therapeutic insights. Biochem Anal Biochem. 2016;5:255.
- Wei H, et al Anti-oxidative stress and anti-apoptosis effects of heyinganxin-formula. J Pharmacogn Nat Prod. 2016;2:115.
- Cemile MS and Çigdem E. The effects of oxidative stress and some of the popular antioxidants on reproductive system:a mini review. J Nutr Food Sci. 2016;6:464.
- Sadhukhan P, et al. Targeting oxidative stress:a novel approach in mitigating cancer. Biochem Anal Biochem. 2015;4:236.
- Hatem E and Azzi S. Oxidative stress in carcinogenesis and therapy. J Cell Signal. 2015;1:102.
- Meher S, et al. Pathophysiology of oxidative stress and antioxidant therapy in acute pancreatitis. J MolBiomarkDiagn. 2015;6:257.
- Dada R, et al. Yoga and meditation as a therapeutic intervention in oxidative stress and oxidative dna damage to paternal genome. J Yoga PhysTher. 2015;5:217.
- Hamma SA, et al.Oxidative stress in algerian adults obesity. J Metabolic Synd. 2015;4:188.
- Avilés-Plaza F, et al. Biomarkers of oxidative stress in syndrome metabolic patients, a case control study. J Metabolic Synd. 2015;4:187.