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Metformin does not prevent DNA damage in lymphocytes despite its antioxidant properties against cumene hydroperoxide-induced oxidative stress.
Mutat Res. 2006 Dec 10; 611(1-2):1-8.MR

Abstract

Metformin (1-(diaminomethylidene)-3,3-dimethyl-guanidine), which is the most commonly prescribed oral antihyperglycaemic drug in the world, was reported to have several antioxidant properties such as the inhibition of advanced glycation end-products. In addition to its use in the treatment of diabetes, it has been suggested that metformin may be a promising anti-aging agent. The present work was aimed at assessing the possible protective effects of metformin against DNA-damage induction by oxidative stress in vitro. The effects of metformin were compared with those of N-acetylcysteine (NAC). For this purpose, peripheral blood lymphocytes from aged (n=10) and young (n=10) individuals were pre-incubated with various concentrations of metformin (10-50microM), followed by incubation with 15microM cumene hydroperoxide (CumOOH) for 48h, under conditions of low oxidant level, which do not induce cell death. Protection against oxidative DNA damage was evaluated by use of the Comet assay and the cytokinesis-block micronucleus technique. Changes in the levels of malondialdehyde+4-hydroxy-alkenals, an index of oxidative stress, were also measured in lymphocytes. At concentrations ranging from 10microM to 50microM, metformin did not protect the lymphocytes from DNA damage, while 50microM NAC possessed an effective protective effect against CumOOH-induced DNA damage. Furthermore, NAC, but not metformin, inhibited DNA fragmentation induced by CumOOH. In contrast to the lack of protection against oxidative damage in lymphocyte cultures, metformin significantly protected the cells from lipid peroxidation in both age groups, although not as effective as NAC in preventing the peroxidative damage at the highest doses. Within the limitations of this study, the results indicate that pharmacological concentrations of metformin are unable to protect against DNA damage induced by a pro-oxidant stimulus in cultured human lymphocytes, despite its antioxidant properties.

Authors+Show Affiliations

Onaran I
Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. ilonaran@istanbul.edu.tr
Guven GS
No affiliation info available
Ozdaş SB
No affiliation info available
Kanigur G
No affiliation info available
Vehid S
No affiliation info available

MeSH

AcetylcysteineAdultAgedAged, 80 and overAntioxidantsBenzene DerivativesCells, CulturedComet AssayDNA DamageDNA FragmentationFemaleHumansHypoglycemic AgentsLipid PeroxidationLymphocytesMaleMalondialdehydeMetforminOxidative Stress

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17000131

Clinical Trial Links

Effect of Melatonin and Metformin on Glycemic Control Genotoxicity and Cytotoxicity Markers in Patients With Prediabetes

Citation

Onaran, Ilhan, et al. "Metformin Does Not Prevent DNA Damage in Lymphocytes Despite Its Antioxidant Properties Against Cumene Hydroperoxide-induced Oxidative Stress." Mutation Research, vol. 611, no. 1-2, 2006, pp. 1-8.
Onaran I, Guven GS, Ozdaş SB, et al. Metformin does not prevent DNA damage in lymphocytes despite its antioxidant properties against cumene hydroperoxide-induced oxidative stress. Mutat Res. 2006;611(1-2):1-8.
Onaran, I., Guven, G. S., Ozdaş, S. B., Kanigur, G., & Vehid, S. (2006). Metformin does not prevent DNA damage in lymphocytes despite its antioxidant properties against cumene hydroperoxide-induced oxidative stress. Mutation Research, 611(1-2), 1-8.
Onaran I, et al. Metformin Does Not Prevent DNA Damage in Lymphocytes Despite Its Antioxidant Properties Against Cumene Hydroperoxide-induced Oxidative Stress. Mutat Res. 2006 Dec 10;611(1-2):1-8. PubMed PMID: 17000131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin does not prevent DNA damage in lymphocytes despite its antioxidant properties against cumene hydroperoxide-induced oxidative stress. AU - Onaran,Ilhan, AU - Guven,Gulgun S, AU - Ozdaş,Sule Beyhan, AU - Kanigur,Gonul, AU - Vehid,Suphi, Y1 - 2006/09/26/ PY - 2005/10/27/received PY - 2006/03/29/revised PY - 2006/06/25/accepted PY - 2006/9/27/pubmed PY - 2007/1/24/medline PY - 2006/9/27/entrez SP - 1 EP - 8 JF - Mutation research JO - Mutat Res VL - 611 IS - 1-2 N2 - Metformin (1-(diaminomethylidene)-3,3-dimethyl-guanidine), which is the most commonly prescribed oral antihyperglycaemic drug in the world, was reported to have several antioxidant properties such as the inhibition of advanced glycation end-products. In addition to its use in the treatment of diabetes, it has been suggested that metformin may be a promising anti-aging agent. The present work was aimed at assessing the possible protective effects of metformin against DNA-damage induction by oxidative stress in vitro. The effects of metformin were compared with those of N-acetylcysteine (NAC). For this purpose, peripheral blood lymphocytes from aged (n=10) and young (n=10) individuals were pre-incubated with various concentrations of metformin (10-50microM), followed by incubation with 15microM cumene hydroperoxide (CumOOH) for 48h, under conditions of low oxidant level, which do not induce cell death. Protection against oxidative DNA damage was evaluated by use of the Comet assay and the cytokinesis-block micronucleus technique. Changes in the levels of malondialdehyde+4-hydroxy-alkenals, an index of oxidative stress, were also measured in lymphocytes. At concentrations ranging from 10microM to 50microM, metformin did not protect the lymphocytes from DNA damage, while 50microM NAC possessed an effective protective effect against CumOOH-induced DNA damage. Furthermore, NAC, but not metformin, inhibited DNA fragmentation induced by CumOOH. In contrast to the lack of protection against oxidative damage in lymphocyte cultures, metformin significantly protected the cells from lipid peroxidation in both age groups, although not as effective as NAC in preventing the peroxidative damage at the highest doses. Within the limitations of this study, the results indicate that pharmacological concentrations of metformin are unable to protect against DNA damage induced by a pro-oxidant stimulus in cultured human lymphocytes, despite its antioxidant properties. SN - 0027-5107 UR - https://www.unboundmedicine.com/medline/citation/17000131/Metformin_does_not_prevent_DNA_damage_in_lymphocytes_despite_its_antioxidant_properties_against_cumene_hydroperoxide_induced_oxidative_stress_ DB - PRIME DP - Unbound Medicine ER -