The Open Clinical Biochemistry Journal


Formerly: The Open Clinical Chemistry Journal

(Discontinued)

ISSN: 2588-7785 ― Volume 9, 2019
RESEARCH ARTICLE

The Effect of Lycopene Treatment on Oxidative DNA Damage of Experimental Diabetic Rats



F. Karahan1, S. Dede1, *, E. Ceylan2
1 Biochemistry Department, Veterinary Medicine School, Van Yuzuncu Yil University, Van, 65080, Turkey.
2 Internal Disease Department, Veterinary Medicine School, Ankara University, Ankara, Turkey

Abstract

Objective:

Lycopene is a carotenoid with anti-inflammatory and antioxidant properties. The aim of this study was to determine the effects of lycopene on oxidative DNA damage levels in experimental diabetic rats.

Subjects and Methods:

Four experimental groups, each consisting of 7 rats, were prepared as Controls, Diabetes (D), Lycopene-treated diabetes (DL) and Lycopene (L). STZ (45 mg/kg) was administered to the diabetic groups intraperitoneally in a single dose. Lycopene was administered to the L and DL groups (10 mg lycopene/kg/day). The test procedure continued for four weeks. To understand the occurrence of diabetic conditions, serum glucose and HbA1c% in the whole blood were determined. The 8-OHdG levels, a marker of oxidative DNA damage, were determined in the blood serum.

Results:

Blood glucose and HbA1c% were higher in the DL group than in the control group and L group (p <0.05) and lower in the D group (p <0.05). 8-OHdG levels were higher in D group than the other groups (p <0.05) while 8-OHdG levels in DL group were lower than D group (p <0.05) and approximated to the control group.

Conclusion:

It can be suggested that lycopene may be described as a protective agent to prevent oxidative DNA damage originated from diabetes.

Keywords: Oxidative DNA damage, Diabetes, Lycopene, Rats, STZ, Mutagenesis.


Article Information


Identifiers and Pagination:

Year: 2018
Volume: 8
First Page: 1
Last Page: 6
Publisher Id: TOCCHEMJ-8-1
DOI: 10.2174/2588778501808010001

Article History:

Received Date: 13/2/2018
Revision Received Date: 8/3/2018
Acceptance Date: 31/3/2018
Electronic publication date: 30/04/2018
Collection year: 2018

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© 2018 Karahan et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Biochemistry Department, Van Yuzuncu Yil University, Veterinary Medicine School, Van, 65080, Turkey; Tel: +904322251027/1520; Fax: +904322251127; E-mail: sdede@yyu.edu.tr





1. INTRODUCTION

Diabetes mellitus is a widespread disease with high morbidity and early mortality rates leading to vascular, renal, retinal or neuropathic disorders and acute metabolic complications due to prolonged hyperglycemia [1Diagnosis and classification of diabetes mellitus. Diabetes Care 2011; 34(Suppl. 1): S62-9.
[http://dx.doi.org/10.2337/dc11-S062] [PMID: 21193628]
].

All the changes in the molecular integrity of the genetic material with the effect of exogenous or endogenous factors are referred as “DNA damage”. Reactive oxygen species such as superoxide and hydroxyl radicals create various lesions which include 8-oxoguanine. It is known that oxidative stress induces oxidative DNA damage, which may lead to mutagenesis [2Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: Mechanisms, mutation, and disease. FASEB J 2003; 17(10): 1195-214.
[http://dx.doi.org/10.1096/fj.02-0752rev] [PMID: 12832285]
-4Matos HR, Capelozzi VL, Gomes OF, Mascio PD, Medeiros MHG. Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate. Arch Biochem Biophys 2001; 396(2): 171-7.
[http://dx.doi.org/10.1006/abbi.2001.2611] [PMID: 11747294]
].

8-OHdG is the most commonly known oxidative DNA damage biomarker formed through free radicals and the direct photodynamic action. The increase in the amount of 8-OHdG depends on several pathological situations including cancer, diabetes and hypertension as well as the aging process. 8-OHdG can be found in tissue, serum, urine and other biological materials [5Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res 1997; 387(3): 147-63.
[http://dx.doi.org/10.1016/S1383-5742(97)00035-5] [PMID: 9439711]
-7Loft S, Deng XS, Tuo J, Wellejus A, Sørensen M, Poulsen HE. Experimental study of oxidative DNA damage. Free Radic Res 1998; 29(6): 525-39.
[http://dx.doi.org/10.1080/10715769800300571] [PMID: 10098457]
]. The emergence of 8-OHdG as a measure of DNA oxidation has resulted in a new follow-up in the evaluation of oxidative DNA damage as frequently observed especially in diabetes, cardiovascular diseases and cancer [8Prabhakar S, Starnes J, Shi S, Lonis B, Tran R. Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production. J Am Soc Nephrol 2007; 18(11): 2945-52.
[http://dx.doi.org/10.1681/ASN.2006080895] [PMID: 17928507]
].

Lipid peroxidation is known to increase in patients with diabetes. Oxidative stress plays an important role in Type 2 diabetes and pathogenesis of its complications. The studies conducted for this purpose reported that 8-OHdG is significant for the measurement of biomarkers such as malondialdehyde (MDA) and determining the status of oxidative stress in organisms [9Piconi L, Quagliaro L, Ceriello A. Oxidative stress in diabetes. Clin Chem Lab Med 2003; 41(9): 1144-9.
[http://dx.doi.org/10.1515/CCLM.2003.177] [PMID: 14598863]
].

Lycopene is thought to have a potential role as an effective antioxidant in the prevention of chronic diseases associated with oxidative stress, and thus attracts a serious scientific interest [10Li ZZ, Lu XZ, Ma CC, Chen L. Serum lycopene levels in patients with diabetic retinopathy. Eur J Ophthalmol 2010; 20(4): 719-23.
[http://dx.doi.org/10.1177/112067211002000412] [PMID: 20099237]
, 11Zhu J, Wang CG, Xu YG. Lycopene attenuates endothelial dysfunction in streptozotocin-induced diabetic rats by reducing oxidative stress. Pharm Biol 2011; 49(11): 1144-9.
[http://dx.doi.org/10.3109/13880209.2011.574707] [PMID: 21517710]
]. Lycopene is a pigment belonging to the carotenoid family found naturally in many fruits and vegetables, especially in tomatoes and tomato products [12Breinholt V, Lauridsen ST, Daneshvar B, et al. Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat. Cancer Lett 2000; 154(2): 201-10.
[http://dx.doi.org/10.1016/S0304-3835(00)00401-8] [PMID: 10806309]
, 13Erhardt JG, Meisner C, Bode JC, Bode C. Lycopene, beta-carotene, and colorectal adenomas. Am J Clin Nutr 2003; 78(6): 1219-24.
[http://dx.doi.org/10.1093/ajcn/78.6.1219] [PMID: 14668286]
]. In patients with Type 2 diabetes, consumption of tomato juice significantly reduced oxidized 'bad' cholesterol and significantly increased plasma lycopene levels [14Coyne T, Ibiebele TI, Baade PD, et al. Diabetes mellitus and serum carotenoids: Findings of a population-based study in Queensland, Australia. Am J Clin Nutr 2005; 82(3): 685-93.
[http://dx.doi.org/10.1093/ajcn/82.3.685] [PMID: 16155284]
].

This study has been designed to investigate the significant role of lycopene implementation on experimental diabetic rats, and the possible role of lycopene in the prevention of the complications of diabetes through observing oxidative DNA damage measurement of 8-OHdG levels.

2. MATERIALS AND METHODS

In this study, 28 male Wistar-Albino male rats weighing 200-250 g were used as materials. Rats were kept in cages in dark/light at a temperature of 22±2°C for 12 hours with permanent food and fresh water throughout the study (4 weeks). Experiments were conducted under the supervision of Van Yuzuncu Yil University Animal Experiments Local Ethics Committee.

The rats were randomly divided to control (C), diabetes (D), diabetes+lycopene (DL) and lycopene (L) groups with each group including 7 rats.

Control group: Only one dose was administered as Physiological serum was administered just one dose (i.p.).

Diabetes group (D): 45 mg/kg single dose STZ (Sigma, USA) prepared in pH 4.5 citrate buffer was applied (i.p.). After 72 hours, blood samples were taken from the tail vein and glucose levels were measured with the PlusMED Accuro (Istanbul, Turkey) brand glucose meter. The rats with a blood glucose of 270 mg/dl and above were considered diabetic and included in the study.

Diabetes+lycopene group (DL): Blood glucose levels of 270 mg/dl and above were determined with a similar treatment in the diabetes group. Lycopene (redivivoTM 10% FS, DSM, Nutritional Products Ltd., Basel, Switzerland) was dissolved orally in corn oil and administered orally at a dose of 10 mg/kg/day for 28 days.

Lycopene group (L): Lycopene was dissolved in corn oil, administered orally at a dose of 10 mg/kg/day for 28 days.

At the end of the 4-week trial, blood samples were taken from the left ventricle of the heart under ketamine anesthesia. In blood samples taken from the tail vein, glucose levels were determined, and HbA1c levels were determined in a blood serum with a commercial kit (Roche Diagnostics GmbH, D-68298 Mannheim, Germany) and an autoanalyzer (Hitachi-911, Roche Diagnostics, Indianapolis, IN). The oxidative DNA damage marker 8-OHdG was measured by EIA kit (Catalog Number: ADI-EKS-3501, Enzo Life Science) with ELISA (Anthus 20 rt brand, Austria).

The data from control and experimental groups were analyzed with a One-Way Variance analysis and the Post Hoc Tests (equal variances not assumed) was applied for multiple comparisons. Differences were considered significant at p<0.05.

3. RESULTS AND DISCUSSION

The results obtained are summarized in Table 1.

Table 1
The results obtained for this study.


Data were expressed as Mean±SE, Differences were considered significant at P<0.05, There are no differences between groups with same letter.

The highest blood glucose and HbA1c levels were determined in experimental diabetic (D) group (p<0.05), as expected. These diabetic markers in DL group were significantly higher than the control group and lycopene (L) group (p<0.05), but significantly lower than diabetic group (p<0.05). There was a statistically significant difference between control and L groups.

The oxidative DNA damage was the highest (p<0.05) in D group. No statistically significant difference was determined in 8-OHdG in control and L groups. 8-OHdG levels significantly decreased in DL group (following lycopene implementation) compared to the D group, and no significant difference was observed compared to control and L groups (p>0.05).

The increase of the prevalence of diabetes with morbidity and mortality requires additional development of preventive and therapeutic strategies. As an alternative to existing methods, new biomarkers are required to be used in the treatment, control and the determination of the risk. An indicator of intracellular oxidative stress which can be used as a potentially valuable biological marker in diabetes is 8-OHdG, a DNA oxidation product [15Broedbaek K, Weimann A, Stovgaard ES, Poulsen HE. Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine as a biomarker in type 2 diabetes. Free Radic Biol Med 2011; 51(8): 1473-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.07.007] [PMID: 21820047]
].

Experimental and epidemiological studies conducted recently reported that regular consumption of carotenoids (including lycopene) rich in fruits and vegetables has a significant role in the prevention of chronic diseases caused by oxidative stress [10Li ZZ, Lu XZ, Ma CC, Chen L. Serum lycopene levels in patients with diabetic retinopathy. Eur J Ophthalmol 2010; 20(4): 719-23.
[http://dx.doi.org/10.1177/112067211002000412] [PMID: 20099237]
, 13Erhardt JG, Meisner C, Bode JC, Bode C. Lycopene, beta-carotene, and colorectal adenomas. Am J Clin Nutr 2003; 78(6): 1219-24.
[http://dx.doi.org/10.1093/ajcn/78.6.1219] [PMID: 14668286]
, 14Coyne T, Ibiebele TI, Baade PD, et al. Diabetes mellitus and serum carotenoids: Findings of a population-based study in Queensland, Australia. Am J Clin Nutr 2005; 82(3): 685-93.
[http://dx.doi.org/10.1093/ajcn/82.3.685] [PMID: 16155284]
].

Serum carotenoids including lycopene are closely related to Type 2 diabetes and decrease linearly in conditions that impair glucose metabolism [14Coyne T, Ibiebele TI, Baade PD, et al. Diabetes mellitus and serum carotenoids: Findings of a population-based study in Queensland, Australia. Am J Clin Nutr 2005; 82(3): 685-93.
[http://dx.doi.org/10.1093/ajcn/82.3.685] [PMID: 16155284]
]. In a study of serum lycopene levels in diabetic patients, Li et al. [10Li ZZ, Lu XZ, Ma CC, Chen L. Serum lycopene levels in patients with diabetic retinopathy. Eur J Ophthalmol 2010; 20(4): 719-23.
[http://dx.doi.org/10.1177/112067211002000412] [PMID: 20099237]
] reported lower lycopene levels in a diabetic group than the control group and a negative correlation between HbA1c and serum lycopene levels. Some researchers report that the beneficial effect of lycopene in the treatment and prophylaxis of diabetic complications is achieved by increasing the antioxidant capacity [10Li ZZ, Lu XZ, Ma CC, Chen L. Serum lycopene levels in patients with diabetic retinopathy. Eur J Ophthalmol 2010; 20(4): 719-23.
[http://dx.doi.org/10.1177/112067211002000412] [PMID: 20099237]
, 14Coyne T, Ibiebele TI, Baade PD, et al. Diabetes mellitus and serum carotenoids: Findings of a population-based study in Queensland, Australia. Am J Clin Nutr 2005; 82(3): 685-93.
[http://dx.doi.org/10.1093/ajcn/82.3.685] [PMID: 16155284]
]. In a study on STZ-induced experimental diabetic rats, Ali and Agha [16Ali MM, Agha FG. Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene. Scand J Clin Lab Invest 2009; 69(3): 371-9.
[http://dx.doi.org/10.1080/00365510802658473] [PMID: 19148834]
] reported hypoglycemic, hypolipidemic and antioxidant effects of lycopene at different doses. Kuhad and Chopra [17Kuhad A, Chopra K. Lycopene ameliorates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rat. Indian J Exp Biol 2008; 46(2): 108-11.
[PMID: 18335808]
] identified the significance of lycopene administration in experimental diabetic rats as adjuvant therapy in the treatment of diabetic neuropathy. In our laboratory, a project on the effects of lycopene on pro-oxidant/total antioxidant status in diabetic rats using the same experimental method [18Yüztaş E. The effects of lycopene on prooxidant/total antioxidant status and vitamin levels in experimental diabetic rats 2001.], lipid peroxidation increased in the diabetic group and total antioxidant status decreased compared to the control and lycopene groups (p<0,001). In the present study, blood glucose and HbA1c% levels were the highest (p<0.05) in experimental diabetic group and decreased significantly in diabetes+lycopene group (p<0.05), however, were still higher (p<0.05) compared to control and lycopene-treated groups. There was no statistically significant difference between control and lycopene groups.

The data obtained from the evaluation of the blood glucose and HbA1c% levels prove that lycopene implementation in experimental diabetic rats may have beneficial effects on impaired glucose metabolism. In fact, the data suggesting that lycopene implementation in the treatment and prophylaxis of diabetic complications is effective by increasing the antioxidant capacity supports this idea [10Li ZZ, Lu XZ, Ma CC, Chen L. Serum lycopene levels in patients with diabetic retinopathy. Eur J Ophthalmol 2010; 20(4): 719-23.
[http://dx.doi.org/10.1177/112067211002000412] [PMID: 20099237]
, 16Ali MM, Agha FG. Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene. Scand J Clin Lab Invest 2009; 69(3): 371-9.
[http://dx.doi.org/10.1080/00365510802658473] [PMID: 19148834]
].

As a result of the statistical evaluation of 8-OHdG levels obtained in this study, oxidative DNA damage was observed the highest (p<0.05) in the experimental diabetic group. There was no statistically significant difference in 8-OHdG in control and lycopene groups. 8-OHdG levels in diabetes+lycopene group significantly (p<0.05) decreased following the lycopene implementation compared to diabetic group and approximated to control and lycopene-treated groups.

According to some researchers, DNA damage in diabetic individuals increases almost three times compared to the controls [19Kasznicki J, Kosmalski M, Sliwinska A, et al. Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy. Mol Biol Rep 2012; 39(9): 8669-78.
[http://dx.doi.org/10.1007/s11033-012-1722-9] [PMID: 22718504]
, 20Park KS, Kim JH, Kim MS, et al. Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats. Diabetes 2001; 50(12): 2837-41.
[http://dx.doi.org/10.2337/diabetes.50.12.2837] [PMID: 11723068]
]. In our study, significantly higher 8-OHdG levels in diabetes group than the other experimental groups were consistent with the literature. Lycopene as an antioxidant increases the total antioxidant potential and decreases oxidative damage by catching reactive oxygen species. Furthermore, supplemental lycopene regulates gene functions and intracellular communication, stimulates hormones and the immune response or regulates the metabolism, thus reduces the risk of chronic disease [21Neyestani TR, Shariatzadeh N, Gharavi A, Kalayi A, Khalaji N. Physiological dose of lycopene suppressed oxidative stress and enhanced serum levels of immunoglobulin M in patients with Type 2 diabetes mellitus: A possible role in the prevention of long-term complications. J Endocrinol Invest 2007; 30(10): 833-8.
[http://dx.doi.org/10.1007/BF03349224] [PMID: 18075285]
, 22Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP. Lycopene as a natural protector against gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes in vitro. Biochim Biophys Acta 2007; 1770(4): 659-65.
[http://dx.doi.org/10.1016/j.bbagen.2006.11.008] [PMID: 17189673]
].

Many studies investigating the effects of lycopene implementation on the oxidative DNA damage reported that there were positive effects of lycopene on DNA damage [23Watters JL, Satia JA, Kupper LL, Swenberg JA, Schroeder JC, Switzer BR. Associations of antioxidant nutrients and oxidative DNA damage in healthy African-American and white adults. Cancer Epidemiol Biomarkers Prev 2007; 16(7): 1428-36.
[http://dx.doi.org/10.1158/1055-9965.EPI-06-1030] [PMID: 17627008]
]. Carotenoids can inhibit DNA damage in experimental animals and humans, which is closely related to the dosing [24Azqueta A, Collins AR. Carotenoids and DNA damage. Mutat Res 2012; 733(1-2): 4-13.
[http://dx.doi.org/10.1016/j.mrfmmm.2012.03.005] [PMID: 22465157]
, 25Scolastici C, Alves de Lima RO, Barbisan LF, Ferreira AL, Ribeiro DA, Salvadori DM. Lycopene activity against chemically induced DNA damage in Chinese hamster ovary cells. Toxicol In Vitro 2007; 21(5): 840-5.
[http://dx.doi.org/10.1016/j.tiv.2007.01.020] [PMID: 17350795]
]. Lycopene implementation has been determined to decrease oxidative DNA degradation and urinary 8-OHdG levels [26Devaraj S, Mathur S, Basu A, et al. A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr 2008; 27(2): 267-73.
[http://dx.doi.org/10.1080/07315724.2008.10719699] [PMID: 18689558]
], as by both completely inhibiting the creation of Comet and reducing 8-OHdG levels [27Huang CS, Hu ML. Lycopene inhibits DNA damage and reduces hMTH1 mRNA expression in the liver of Mongolian gerbils treated with ferric nitrilotriacetate. Food Chem Toxicol 2011; 49(6): 1381-6.
[http://dx.doi.org/10.1016/j.fct.2011.03.023] [PMID: 21421019]
]. Moreover, in this study, although 8-OHdG levels in the diabetic group have increased substantially than all other experimental groups (p<0.05), it has been determined that 8-OHdG levels in DL group were considerably lower than diabetes. 8-OHdG levels being significantly lower in lycopene-treated diabetic group (DL) and being close to the control and lycopene groups was regarded as a data supporting the positive effects of lycopene reducing the DNA damage. As a result, although blood glucose and HbA1c% levels in lycopene-treated diabetic group (DL) have increased compared to the control and lycopene-treated groups, it was determined significantly lower than the diabetic group. The decrease in glucose and HbA1 levels after lycopene treatment may be an evidence for restoring the islet cells damaged by streptozotocin, and likewise, 8-OHdG levels can be an indicator for prevention by lycopene.

CONCLUSION

Although 8-OHdG levels significantly increased in diabetic group than in the other experimental groups, lycopene implementation has beneficial effect on this level to the control and lycopene groups. It is thought to have beneficial effects for the protection of genetic material in diabetic individuals and hence for the treatment and prevention of complications due to diabetes. 8-OHdG levels in the lycopene group and the control group were considered as a benchmark supporting the fact that the lycopene dose used is within reliable limits for this study. This study can be considered as a preliminary study for future studies for different doses, times and other oxidation parameters can be used to explore the possible role of carotenoids in the pathogenesis, treatment and protection of insulin resistance and diabetes.

FUNDING

This work was supported by Yuzuncu Yil University Scientific Research Projects Fund (grant number: 925 2010-SBE-YL 164).

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Experiments were conducted under the supervision of Van Yuzuncu Yil University Animal Experiments Local Ethics Committee.

HUMAN AND ANIMAL RIGHTS

No humans were involved in this study. The reported experiments were in accordance with the standards set forth in the 8th Edition of Guide for the Care and Use of Laboratory Animals (http:// grants.nih.gov/grants/olaw/Guide-for-thecare-and-use-of-laboratory-animals.pdf).

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

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[3] Kulaksız G, Sancar A. Nukleotid eksizyon onarımı ve kanser. Turk J Biochem 2007; 32(3): 104-11.
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[http://dx.doi.org/10.1006/abbi.2001.2611] [PMID: 11747294]
[5] Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res 1997; 387(3): 147-63.
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[http://dx.doi.org/10.1515/CCLM.2003.177] [PMID: 14598863]
[10] Li ZZ, Lu XZ, Ma CC, Chen L. Serum lycopene levels in patients with diabetic retinopathy. Eur J Ophthalmol 2010; 20(4): 719-23.
[http://dx.doi.org/10.1177/112067211002000412] [PMID: 20099237]
[11] Zhu J, Wang CG, Xu YG. Lycopene attenuates endothelial dysfunction in streptozotocin-induced diabetic rats by reducing oxidative stress. Pharm Biol 2011; 49(11): 1144-9.
[http://dx.doi.org/10.3109/13880209.2011.574707] [PMID: 21517710]
[12] Breinholt V, Lauridsen ST, Daneshvar B, et al. Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat. Cancer Lett 2000; 154(2): 201-10.
[http://dx.doi.org/10.1016/S0304-3835(00)00401-8] [PMID: 10806309]
[13] Erhardt JG, Meisner C, Bode JC, Bode C. Lycopene, beta-carotene, and colorectal adenomas. Am J Clin Nutr 2003; 78(6): 1219-24.
[http://dx.doi.org/10.1093/ajcn/78.6.1219] [PMID: 14668286]
[14] Coyne T, Ibiebele TI, Baade PD, et al. Diabetes mellitus and serum carotenoids: Findings of a population-based study in Queensland, Australia. Am J Clin Nutr 2005; 82(3): 685-93.
[http://dx.doi.org/10.1093/ajcn/82.3.685] [PMID: 16155284]
[15] Broedbaek K, Weimann A, Stovgaard ES, Poulsen HE. Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine as a biomarker in type 2 diabetes. Free Radic Biol Med 2011; 51(8): 1473-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.07.007] [PMID: 21820047]
[16] Ali MM, Agha FG. Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene. Scand J Clin Lab Invest 2009; 69(3): 371-9.
[http://dx.doi.org/10.1080/00365510802658473] [PMID: 19148834]
[17] Kuhad A, Chopra K. Lycopene ameliorates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rat. Indian J Exp Biol 2008; 46(2): 108-11.
[PMID: 18335808]
[18] Yüztaş E. The effects of lycopene on prooxidant/total antioxidant status and vitamin levels in experimental diabetic rats 2001.
[19] Kasznicki J, Kosmalski M, Sliwinska A, et al. Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy. Mol Biol Rep 2012; 39(9): 8669-78.
[http://dx.doi.org/10.1007/s11033-012-1722-9] [PMID: 22718504]
[20] Park KS, Kim JH, Kim MS, et al. Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats. Diabetes 2001; 50(12): 2837-41.
[http://dx.doi.org/10.2337/diabetes.50.12.2837] [PMID: 11723068]
[21] Neyestani TR, Shariatzadeh N, Gharavi A, Kalayi A, Khalaji N. Physiological dose of lycopene suppressed oxidative stress and enhanced serum levels of immunoglobulin M in patients with Type 2 diabetes mellitus: A possible role in the prevention of long-term complications. J Endocrinol Invest 2007; 30(10): 833-8.
[http://dx.doi.org/10.1007/BF03349224] [PMID: 18075285]
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Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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