Does metformin prevent short-term oxidant-induced dna damage? In vitro study on lymphocytes from aged subjects.
Metformin(1-(diaminomethylidene)-3,3-dimethyl-guanidine), an anti-hyperglycemic agent, also has antioxidant effects. Although the origin is not clearly understood, the antioxidant activity of metformin might result from a direct effect on reactive oxygen species (ROS) or could have an indirect action on the superoxide anions produced by hyperglycemia. The ability of metformin to modulate DNA damage produced by oxidative stress is not known. For this reason, we examined the short term effect of metformin (50 microM, 2 h) on the DNA damage of cumene hydroperoxide (CumOOH)-induced lymphocytes from aged and young control groups (n = 10 each). In this study, DNA damage elicited by CumOOH (1 mM) was detected with the Comet Assay and the ELISA technique. Our results showed a significant increase in apoptotic DNA fragmentation and DNA strand breaks (Comet assay tail factor %) that was detected before and after CumOOH induction in lymphocytes of healthy elderly subjects when compared with healthy young control. Metformin significantly decreased CumOOH-induced apoptotic DNA fragmentation and DNA strand breaks in lymphocytes from aged subjects, although it did not produce a long-term effect. The in vitro results indicate that the short-term effect of metformin can protect against prooxidant stimulus-induced DNA damage in lymphocytes from elderly subjects.
Kanigür-Sultuybek
Gönül
G
Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Turkey.
Ozdas
Sule Beyhan
SB
Curgunlu
Asli
A
Tezcan
Vecdet
V
Onaran
Ilhan
I
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D001555:Benzene Derivatives / Q000633:toxicity; D020552:Comet Assay; D053960:DNA Breaks; D053938:DNA Fragmentation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008214:Lymphocytes; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
D000975:Antioxidants; D001555:Benzene Derivatives; D007004:Hypoglycemic Agents; D008687:Metformin; C007164:cumene hydroperoxide