Danilo J Xavier1, Paula Takahashi1, Fernanda S Manoel-Caetano2, Maria C Foss-Freitas3, Milton C Foss3, Eduardo A Donadi4, Geraldo A Passos5, Elza T Sakamoto-Hojo6. 1. Department of Genetics, Faculty of Medicine of Ribeirão Preto (FMRP), University of São Paulo-USP, Ribeirão Preto, SP, Brazil. 2. Department of Genetics, Faculty of Medicine of Ribeirão Preto (FMRP), University of São Paulo-USP, Ribeirão Preto, SP, Brazil; Department of Biology, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto (FFCLRP), University of São Paulo-USP, Ribeirão Preto, SP, Brazil. 3. Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto, SP, Brazil. 4. Department of Genetics, Faculty of Medicine of Ribeirão Preto (FMRP), University of São Paulo-USP, Ribeirão Preto, SP, Brazil; Division of Clinical Immunology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto, SP, Brazil. 5. Department of Genetics, Faculty of Medicine of Ribeirão Preto (FMRP), University of São Paulo-USP, Ribeirão Preto, SP, Brazil; Disciplines of Genetics and Molecular Biology, Department of Morphology, Faculty of Dentistry of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto, SP, Brazil. 6. Department of Genetics, Faculty of Medicine of Ribeirão Preto (FMRP), University of São Paulo-USP, Ribeirão Preto, SP, Brazil; Department of Biology, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto (FFCLRP), University of São Paulo-USP, Ribeirão Preto, SP, Brazil. Electronic address: etshojo@usp.br.
Abstract
AIMS: Hyperglycemia leads to increased production of reactive oxygen species (ROS), which reduces cellular antioxidant defenses and induces several DNA lesions. We investigated the effects on DNA damage of a seven-day hospitalization period in patients with type 2 diabetes mellitus (T2DM) to achieve adequate blood glucose levels through dietary intervention and medication treatment, compared with non-diabetic individuals. METHODS: DNA damage levels were evaluated by the alkaline comet assay (with modified and without conventional use of hOGG1 enzyme, which detects oxidized DNA bases) for 10 patients and 16 controls. Real time PCR array method was performed to analyze the transcriptional expression of a set of 84 genes implicated in antioxidant defense and response to oxidative stress in blood samples from T2DM patients (n=6) collected before and after the hospitalization period. RESULTS: The seven-day period was sufficient to improve glycemic control and to significantly decrease (p<0.05) DNA damage levels in T2DM patients, although those levels were slightly higher than those in control subjects. We also found a tendency towards a decrease in the levels of oxidative DNA damage in T2DM patients after the hospitalization period. However, for all genes analyzed, a statistically significant difference in the transcriptional expression levels was not observed. CONCLUSIONS: The study demonstrated that although the transcriptional expression of the genes studied did not show significant alterations, one-week of glycemic control in hospital resulted in a significant reduction in DNA damage levels detected in T2DM patients, highlighting the importance of an adequate glycemic control.
AIMS: Hyperglycemia leads to increased production of reactive oxygen species (ROS), which reduces cellular antioxidant defenses and induces several DNA lesions. We investigated the effects on DNA damage of a seven-day hospitalization period in patients with type 2 diabetes mellitus (T2DM) to achieve adequate blood glucose levels through dietary intervention and medication treatment, compared with non-diabetic individuals. METHODS: DNA damage levels were evaluated by the alkaline comet assay (with modified and without conventional use of hOGG1 enzyme, which detects oxidized DNA bases) for 10 patients and 16 controls. Real time PCR array method was performed to analyze the transcriptional expression of a set of 84 genes implicated in antioxidant defense and response to oxidative stress in blood samples from T2DM patients (n=6) collected before and after the hospitalization period. RESULTS: The seven-day period was sufficient to improve glycemic control and to significantly decrease (p<0.05) DNA damage levels in T2DM patients, although those levels were slightly higher than those in control subjects. We also found a tendency towards a decrease in the levels of oxidative DNA damage in T2DM patients after the hospitalization period. However, for all genes analyzed, a statistically significant difference in the transcriptional expression levels was not observed. CONCLUSIONS: The study demonstrated that although the transcriptional expression of the genes studied did not show significant alterations, one-week of glycemic control in hospital resulted in a significant reduction in DNA damage levels detected in T2DM patients, highlighting the importance of an adequate glycemic control.