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Finecure Update
Lycopherol
A Passi Publication
Oxidative stress causes human diseases
Role of lycopene, alpha-tocopherol, vit. A, vit. C, zinc, and
selenium as anti-oxidant defenses
Oxidative stress in the pathophysiology
of human disorders and diseases
dysfunction can promote vasospasm, thrombosis, vascular
inflammation, and proliferation of the intima.1
Vascular oxidative stress and increased production of reactive
oxygen species contributes to mechanisms of vascular dysfunction
and has been implicated to play an important role in a number of
cardiovascular pathologies, including hypertension, atherosclerosis,
myocardial infarction, ischemia/reperfusion injury, and restenosis
after angioplasty or venous bypass grafting.
The formation of reactive oxygen species is balanced out by
antioxidant defenses, and augmenting this defense by antioxidant
therapies could therefore provide a potential means to treat conditions
in which the formation of reactive oxygen species exceeds the
capability of natural protective mechanisms.2
Oxidative stress is mainly caused by an imbalance between the
activity of endogenous pro–oxidative enzymes (such as NADPH
oxidase, xanthine oxidase or the mitochondrial respiratory chain)
and antioxidant enzymes (such as superoxide dismutase, glutathione
peroxidase, heme oxygenase, thioredoxin peroxidase/peroxiredoxin,
catalase and paraoxonase).
Endogenous reactive intermediates including photoexcited states
of tissue chromophores, reactive oxygen species (ROS), reactive
carbonyl species (RCS), transition metal ions, and Schiff bases have
been implicated in the initiation and progression of diverse human
pathologies including tumorigenesis, atherosclerosis, diabetes, and
neurodegenerative disease. Oxidative stress is also implicated in
the cognitive deterioration associated with normal aging as well as
neurodegenerative disorders such as Alzheimer’s and Parkinson’s
diseases.
immunomodulatory effects of lycopene
There is evidence indicating that regular consumption of tomato
products is associated with favorable immunomodulatory effects. In
addition, tomato extracts have been shown to possess antioxidant,
anticarcinogenic and antithrombotic activity in vitro. The present
work was designed to examine the in vitro effect of lycopene
on cytokine production by peripheral blood mononuclear cells
(PBMC) from 15 healthy subjects. Lycopene is considered to
be a potent antioxidant with benefits in prevention of several
chronic diseases.
Lycopene induced a dose–dependent increase in IL–1beta,
and TNF–alpha production and a decrease in IL–2, IL–10 and
IFN–gamma secretion, whereas IL–6 and IL–1ra was not affected.
Oxidative stress in vascular disease
Endothelial cells control vascular homeostasis by generating
paracrine factors that regulate vascular tone, inhibit platelet function,
prevent adhesion of leukocytes, and limit proliferation of vascular
smooth muscle. The dominant factor responsible for many of those
effects is endothelium–derived nitric oxide (NO).
Endothelial dysfunction characterized by enhanced inactivation
or reduced synthesis of NO, alone or in combination, is seen in
conjunction with risk factors for cardiovascular disease. Endothelial
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Finecure Update
role in the healthy development of the fetus and the newborn, with
lung development and maturation being particularly important.8
The carotenoids, specifically beta–carotene has shown to possess
antioxidant properties. This precursor of vitamin A is considered
the most efficient “quencher” of singlet oxygen.
It was concluded that understanding the role of lycopene in
modulation of the immune system may promote decisions as
for dietary supplementation of lycopene for reducing the risk of
certain diseases.3
Lycopene in the prevention
of prostate cancer
the role of selenium
Selenium functions as a part of proteins known as selenoproteins.
Despite the low selenium content in the body (20–40 mg),
selenoenzymes play an important role in antioxidant defense in
humans. Through these selenoproteins, selenium functions as a
defensive mechanism for oxidative stress, for the regulation of
thyroid hormone activity, and for the redox status of vitamin C
and other molecules.
In several of its roles, selenium functions as a dietary antioxidant
and thus has been studied for its possible role in chronic diseases.9,10
Studies have demonstrated that selenium supplementation reduces
the incidence of cancer, particularly prostate cancer.11
Based on the evidence from epidemiologic, animal, and in vitro
data and human clinical trials, it is evident that lycopene, a non–
provitamin A carotenoid, is a promising agent for prostate cancer
chemoprevention. Based on reviews, there is enough evidence to
warrant use of lycopene in phase I and II clinical trials to examine
its safety and efficacy as a potential chemopreventive agent for
prostate cancer.4
Vitamin E
Vitamin E is a generic term that refers to a family of compounds
that is further divided into two subgroups called tocopherols and
tocotrienols. It comprises eight different isoforms: four tocopherols
(alpha, beta, gamma, and delta) and four tocotrienols (alpha, beta,
gamma, and delta). A wealth of data is available for the preventive
efficacy of alpha–tecopherol. It is an established antioxidant
with an ability to ameliorate the UV–induced skin damage and
chemically–induced inflammation in lungs. alpha–T supplementation
in human subjects and animal models has been shown to be
antioxidant and antiinflammatory in terms of decreasing C–reactive
protein (CRP) and release of proinflammatory cytokines,
the chemokine IL–8 and PAI–1 levels, especially at high doses.5
In patients with moderately severe impairment from Alzheimer’s
disease, treatment with alpha–T slows the progression of
disease. Vitamin E may reduce the risk of developing physically
debilitating disorders, and Vitamin E antioxidants can help
support a strong immune system. Experts also concluded that
in patients with angiographically proven symptomatic coronary
atherosclerosis, alpha–tocopherol treatment substantially reduces
the rate of non–fatal MI, with beneficial effects apparent after 1
year of treatment.6
Effect of vitamin E and selenium
in pulmonary tB patients
Increased production of reactive oxygen species secondary to
phagocyte respiratory burst occurs in pulmonary tuberculosis
(TB). The present study evaluated the efficacy of vitamin
E–selenium on oxidative stress in newly diagnosed patients treated
for pulmonary TB. The intervention group (n = 17) received
vitamin E and selenium (vitamin E: 140 mg alpha–tocopherol and
selenium: 200 microg) and the control group (n = 18) received
placebo. Both groups received standard anti–TB treatment. It
was concluded that a 2–month intervention with vitamin E and
selenium supplementation reduces oxidative stress and enhances
total antioxidant status in patients with pulmonary TB treated with
standard chemotherapy.12
Vitamin C in chronic disease and
effect on clinical conditions
Vitamin C is an essential dietary nutrient required as a co–factor
for many enzymes. The reduced form of the vitamin, ascorbic
acid, is an especially effective antioxidant owing to its high
electron–donating power and ready conversion back to the active
reduced form. The evidence that ascorbic acid acts as an important
antioxidant in many body tissues is convincing.
There is great interest in the clinical roles of vitamin C because
of evidence that oxidative damage is a root cause of, or at least
associated with, many diseases. A large number of randomized
controlled intervention trials document that adequate intakes of
vitamin C ameliorate symptoms and shortens the duration of
respiratory tract infections, including common cold. Furthermore,
vitamin C reduces the incidence and improves outcome of
pneumonia, malaria, and diarrhea infections, especially in children
in developing countries. The new higher Recommended Dietary
Allowance (RDA) for vitamin C of 75 mg for women and 90 mg for
men is, for the first time, based on the vitamin’s role as an antioxidant
as well as protection from deficiency.13,14
Effect of alpha–tocopherol on
antioxidant enzyme status
The relationships between alpha–tocopherol, pro–oxidant and
antioxidant enzyme status, and radiation toxicity were studied in
stage II, III, and IVA oral squamous cell carcinoma patients. It
was seen that alpha–tocopherol played a role in protecting against
the damage caused by irradiation in oral squamous cell carcinoma
patients treated with radiotherapy, by enhancing the antioxidant
enzyme status and reducing the pro–oxidant status.7
VITAMIN A
Vitamin A (retinol), an essential human nutrient, plays an important
role in cellular differentiation, regulation of epidermal cell growth
and normal cell maintenance. Vitamin A also plays an important
role in bone structure and function. Notably during pregnancy and
throughout the breastfeeding period, vitamin A has an important
Drug
Lycopherol
CompositionAdministration
Alphatocopherol Acetate IP 10 mg, Vitamin A Acetate IP 2500 iu, Zinc Sulphate 1 OD
Monohydrate U.S.P. eq to Elemental Zinc 27.45 mg, Lycopene USP 2 mg, Selenium
Dioxide Monohydrate USP 70 mcg, Vitamin C (coated) IP 25 mg
2
Finecure Update
Effects of vitamin e, vitamin
C, and selenium
Dr. Javed Salam MD
Senior Consultant and Head, Department of Medicine,
BJR Hospital, Delhi
Cadmium is a highly toxic metal, having an generation of various
free radiclas. This study was undertaken to examine the effect of
acute cadmium and/or antioxidants on serum lipid metabolism,
tissue glutathione, and lipid peroxidation (LPO) levels, and ghrelin
and metallothionein production in the gastric fundus mucosa.
Antioxidants such as vitamin E, vitamin C, and selenium were
important for preventing the damage caused by reactive oxygen
species.15
Doctor opines...
Premature aging and many life-style diseases
are being seen in earlier than expected age
groups as a result of oxidative stress. I
personally regularly prescribe antioxidants
to patients who I feel need them. I believe lycopherol is a
wholesome and complete package of antioxidants that is effective
in many ways. My patients now have adequate protection from
the increased number of free radicals they are faced with.
effect of selenium, ascorbic acid, beta–
carotene, and alpha–tocopherol
The aim of this study was to investigate the role of selenium, ascorbic
acid, beta–carotene, and alpha–tocopherol on D–Galactosamine
(D–GaLN) induced liver injury. D–GaLN is a highly selective
hepatotoxin that causes liver injury similar to human viral
hepatitis via depletion of uridine nucleotides, which subsequently
diminishes synthesis of RNA and proteins. The results suggested
that supplementation with the combination of selenium, ascorbic
acid, beta–carotene, and alpha–tocopherol may help prevent the
development of liver injury.16
of synaptic pool of zinc in the hippocampus. Clinical observations
demonstrated serum hypozincemia in depression, which was
normalized by effective antidepressant treatment. Moreover,
preliminary clinical study demonstrate the benefit of zinc
supplementation in antidepressant therapy.20
references
1. Förstermann U. Oxidative stress in vascular disease: causes, defense mechanisms and
potential therapies. Nat Clin Pract Cardiovasc Med. 2008 May 6.
2. Levonen AL, Vähäkangas E, Koponen JK, Ylä–Herttuala S. Antioxidant gene
therapy for cardiovascular disease: current status and future perspectives.
Circulation. 2008 Apr 22; 117(16): 2142–50.
3. Bessler H, Salman H, Bergman M, Alcalay Y, Djaldetti M. In vitro effect of lycopene
on cytokine production by human peripheral blood mononuclear cells. Immunol Invest.
2008; 37(3): 183–90.
4. Dahan K, Fennal M, Kumar NB. Lycopene in the prevention of prostate cancer. J Soc
Integr Oncol. 2008 Winter; 6(1): 29–36.
5. Singh U, Devaraj S. Vitamin E: inflammation and atherosclerosis. Vitam Horm. 2007;
76: 519–49.
6. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ.
Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge
Heart Antioxidant Study (CHAOS). Lancet. 1996 Mar 23; 347(9004): 781–6.
7. Chitra S, Shyamala Devi CS. Effect of alpha–tocopherol on pro–oxidant and antioxidant
enzyme status in radiation–treated oral squamous cell carcinoma. Indian J Med Sci.
2008 Apr; 62(4): 141–8.
8. Strobel M, Tinz J, Biesalski HK. The importance of beta–carotene as a source of vitamin
A with special regard to pregnant and breastfeeding women. Eur J Nutr. 2007 Jul; 46
Suppl 1: I1–20.
9. Vincent JL, Forceville X. Critically elucidating the role of selenium. Curr Opin Anaesthesiol. 2008 Apr; 21(2): 148–54.
10. Boosalis MG. The role of selenium in chronic disease. Nutr Clin Pract. 2008 Apr; 23(2):
152–60.
11. Xiang N, Zhao R, Zhong W. Sodium selenite induces apoptosis by generation of superoxide via the mitochondrial–dependent pathway in human prostate cancer cells. Cancer
Chemother Pharmacol. 2008 Apr 1.
12. Seyedrezazadeh E, Ostadrahimi A, Mahboob S, Assadi Y, Ghaemmagami J, Pourmogaddam M. Effect of vitamin E and selenium supplementation on oxidative stress
status in pulmonary tuberculosis patients. Respirology. 2008 Mar; 13(2): 294–8.
13. Wintergerst ES, Maggini S, Hornig DH. Immune–enhancing role of vitamin C and zinc
and effect on clinical conditions. Ann Nutr Metab. 2006; 50(2): 85–94.
14. Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin
Care. 2002 Mar–Apr; 5(2): 66–74.
15. Bolkent S, Sacan O, Yanardag R, Bolkent S. Effects of vitamin e, vitamin C, and selenium on gastric fundus in cadmium toxicity in male rats. Int J Toxicol. 2008 Mar–Apr;
27(2): 217–22.
16. Catal T, Bolkent S. Combination of selenium and three naturally occurring antioxidants
administration protects d: –galactosamine–induced liver injury in rats. Biol Trace Elem
Res. 2008 May; 122(2): 127–36.
17. Stéphan F, Revuz J. [Zinc salts in dermatology] Ann Dermatol Venereol. 2004 May;
131(5): 455–60.
18. Salvatore S, Luini C, Arrigo S, Salmaso M, Morando L, Nespoli L, Vandenplas Y. [Probiotics, prebiotics and zinc in the therapy and prevention of acute infectious diarrhoea in
children: state of the art] Minerva Pediatr. 2007 Dec; 59(6): 775–86.
19. Eter N, Krohne TU, Holz FG. New pharmacologic approaches to therapy for age–related
macular degeneration. BioDrugs. 2006; 20(3): 167–79.
20. Nowak G, Szewczyk B, Pilc A. Zinc and depression. An update. Pharmacol Rep. 2005
Nov–Dec; 57(6): 713–8.
Zinc
Zinc is an essential trace element for the human organism. It
acts like cofactor for the metalloenzymes involved in many
cellular processes.17 In developing countries zinc supplementation
demonstrated a significant reduction of fecal excretion, duration,
severity and persistency of diarrhoea. Moreover, zinc may improve
immune status, intestinal permeability, epithelial and enzymatic
functions, and transport of electrolytes.18
The combination of vitamins C and E, beta–carotene, and zinc
as used in the AREDS (Age–Related Eye Disease Study) reduces
risk for conversion from early– to late–stage disease in patients with
high–risk features, at least to some extent.19
Similar to antidepressants, zinc induces brain derived
neurotrophic factor (BDNF) gene expression and increases level
highlights
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Lycopene, a non-provitamin A carotenoid, is a promising
antioxidant agent for its benefits in prevention of several
chronic diseases
Major studies report that high levels of antioxidant vitamin
E may contribute to overall health
Vitamin A plays an important role in the normal functioning
of the visual system, epithelial cell integrity and growth,
immunity, and reproduction
Beta–carotene has shown to possess antioxidant properties and
is considered the most efficient “quencher” of singlet oxygen
The combination of selenium, ascorbic acid, beta-carotene,
and alpha-tocopherol may help prevent the development of
liver injury
A high-dose of an orally administered combination of the
antioxidants ascorbic acid (vitamin C), tocopherol (vitamin E)
and beta-carotene, in addition to copper and zinc, is the only
widely accepted preventive therapy for age-related macular
degeneration.
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