DNA protective effects of melatonin on oxidative stress in streptozotocin - induced diabetic rats.
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1
Adnan Menderes University Faculty of Veterinary Medicine, Pharmacology and Toxicology, Türkiye
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2
Adnan Menderes University Faculty of Medicine, Anatomy, Türkiye
Diabetes mellitus is a chronic disease characterized by elevated blood sugar levels resulting from either a lack of insulin production or resistance to insulin. As the prevalence of diabetes has risen to epidemic proportions worldwide, complications of diabetes have now become one of the most challenging health problems. Radicals derived from oxygen (ROS) and nitrogen (RNS) are the largest class of radical species generated in living systems. ROS and RNS are products of normal cell metabolism and have either beneficial or deleterious effects, depending on the concentration reached in the tissues (1). In diabetic patients, oxidative stress induced by the presence of excessive ROS and RNS is closely associated with chronic inflammation leading to potential tissue damage. The role of oxidative stress in the development of diabetic endothelial dysfunction is underlined by a number of studies. The development of inhibitors against the main sources of ROS generation could be an alternative approach to conventional antioxidant therapies. One of the main challenges of research in recent years has been finding ways to attenuate oxidative stress in order to improve diabetes. Therefore, it seems reasonable that antioxidants can play an important role in the improvement of diabetes. There are many reports on effects of antioxidants in the management of diabetes. Melatonin (MEL) (N-acetyl-5-methoxytryptamine) is a compound synthesized by the pineal gland in the human brain. MEL is also produced in the retina, thymus, bone marrow, respiratory epithelium, skin, lens, intestine and in other sites. MEL has been characterized as an effective synchronizing agent in several physiological and pathological conditions. MEL is a major scavenger of both ROS and RNS reactive molecules. MEL provokes this effect at both physiological and pharmacological concentrations. Several of its metabolites can also detoxify free radicals and derivatives. With regards to the enzymes of the antioxidant system, MEL regulates the expression of several genes such as those of superoxide dismutase (SOD) and glutathione peroxidase (2-4).
The aim of this study was to research the effects of MEL on oxidative stress and DNA protective effects in streptozotocin-induced diabetic rats. A total of 32 rats were equally divided into 4 experimental groups as Control, Melatonin, Diabetic, and Diabetic + Melatonin. A pancreatic beta-cell cytotoxic agent, single dose streptozotocin (60 mg/kg) was given by intraperitoneal route to induce experimental diabetes in rats. Rats with ≥200mg/dL blood glucose level were established as Diabetic and Diabetic + Melatonin groups. MEL (10 mg/kg per day) and sodium citrate solution were administrated to rats by intraperitoneal route for 6 weeks. With the termination of the experiment, tissue and blood samples were obtained for further analysis. SOD, catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in rat liver, renal, brain and pancreas tissues. Body weight, plasma glucose, and %HbA1c levels were studied. DNA damage was analyzed with the comet assay in rat lymphocytes; %Tail DNA and Mean Tail Moment parameters were evaluated (5).
Antioxidant and oxidant enzyme levels were similar in the Control and Melatonin groups, although there were significant differences between the Diabetic and Diabetic + Melatonin groups. SOD levels in brain and liver tissues were higher (P<0,001), and CAT activities in renal tissue (P<0,001), GSH levels in pancreas tissue (P<0,01) as well as MDA levels in liver (P<0,001), renal (P<0,001) and brain (P<0,01) tissues were higher in the Diabetic + Melatonin group compared with the Diabetic group. Body weight changes and blood glucose levels of the rats were evaluated during the 6 weeks. The effect of MEL on the body weights of Control and Melatonin as well as Diabetic and Diabetic + Melatonin group rats were similar. MEL had no effect on body weight and the diabetic rats were lighter (P<0,001). Also, MEL did not affect blood glucose level and the diabetic rats glucose levels were higher (P<0,001). Blood %HbA1c level was also higher in the diabetic rats (P<0,001) and MEL had no effect on %HbA1c levels. DNA damage was higher in Diabetic group rats (P<0,001), although %Tail DNA and Mean Tail Moment parameters were better in the MEL administered groups than the Diabetic group rats (P<0,001). These results indicate that administration of 10 mg/kg intraperitoneal MEL for 6 weeks may cause amelioration in oxidative stress parameters associated with diabetes, with beneficial effects seen on %Tail DNA and Mean Tail Moment parameters in rat lymphocytes.
Acknowledgements
Adnan Menderes University Scientific Research Projects
References
1.Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem. 2006;52(4):601-23.
2.Carpentieri A, de Barboza GD, Areco V, López MP, de Talamoni NT. New perspectives in melatonin uses. Pharmacol Res. 2012;65(4):437-44.
3.Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother. 2005;59(7):365-73.
4.Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta. 2014;1840(9):2709-29.
5.Collins AR, Azqueta A. DNA repair as a biomarker in human biomonitoring studies; further applications of the comet assay. Mutat Res. 2012;736(1-2):122-9.
Keywords:
Comet Assay,
Oxidative Stress,
Melatonin,
Streptozotocin,
DNA Damage,
Diabetes Mellitus,
Glucose,
HbA1c,
Superoxide Dismutase,
Catalase,
GSH response,
MDA level,
Tail moment,
% Tail DNA,
DNA Repair
Conference:
ICAW 2015 - 11th International Comet Assay Workshop, Antwerpen, Belgium, 1 Sep - 4 Sep, 2015.
Presentation Type:
Oral Presentation
Topic:
Clinical applications of the comet assay
Citation:
Sekkin
S,
İpek
ED,
Boyacioglu
M,
Kum
C,
Karademir
U,
Yalinkilinc
HS,
Ak
MO and
Basaloglu
H
(2015). DNA protective effects of melatonin on oxidative stress in streptozotocin - induced diabetic rats..
Front. Genet.
Conference Abstract:
ICAW 2015 - 11th International Comet Assay Workshop.
doi: 10.3389/conf.fgene.2015.01.00024
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Received:
02 Jun 2015;
Published Online:
23 Jun 2015.
*
Correspondence:
PhD. Selim Sekkin, Adnan Menderes University Faculty of Veterinary Medicine, Pharmacology and Toxicology, Aydin, 09016, Türkiye, ssekkin@gmail.com