Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

*** Oxidative stress in patients with type 2 diabetes mellitus treated with metformin ***AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up.METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients’ questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson’s correlation and Spearman’s correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and end of the study was evaluated using Student’s t-test or Wilcoxon U test. The significance level was set at 5%.RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2, who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient.CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.

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Two Novel Approaches Providing Cardiac Protection Against Oxidative Stress

Novel Strategies in Ischemic Heart Disease ◽

10.5772/31890 ◽

2012 ◽

Author(s):

Howard Prentice ◽

Herbert Weissbach

Keyword(s):

Oxidative Stress ◽

Cardiac Protection ◽

Novel Approaches

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Oxidative-stress-induced epigenetic changes in chronic diabetic complications

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2012-0251 ◽

2013 ◽

Vol 91 (3) ◽

pp. 213-220 ◽

Cited By ~ 36

Author(s):

Biao Feng ◽

Michael Anthony Ruiz ◽

Subrata Chakrabarti

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Protein Kinase ◽

Diabetic Complications ◽

Histone Deacetylases ◽

Excision Repair ◽

Mitogen Activated Protein Kinase ◽

Signal Pathways ◽

Epigenetic Changes ◽

Class Iii

Oxidative stress plays an important role in the development and progression of chronic diabetic complications. Diabetes causes mitochondrial superoxide overproduction in the endothelial cells of both large and small vessels. This increased superoxide production causes the activation of several signal pathways involved in the pathogenesis of chronic complications. In particular, endothelial cells are major targets of glucose-induced oxidative damage in the target organs. Oxidative stress activates cellular signaling pathways and transcription factors in endothelial cells including protein kinase C (PKC), c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), forkhead box O (FOXO), and nuclear factor kappa-B (NF-κB). Oxidative stress also causes DNA damage and activates DNA nucleotide excision repair enzymes including the excision repair cross complimenting 1(ERCC1), ERCC4, and poly(ADP-ribose) polymerase (PARP). Augmented production of histone acetyltransferase p300, and alterations of histone deacetylases, including class III deacetylases sirtuins, are also involved in this process. Recent research has found that small noncoding RNAs, like microRNA, are a new kind of regulator associated with chronic diabetic complications. There are extensive and complicated interactions and among these molecules. The purpose of this review is to demonstrate the role of oxidative stress in the development of diabetic complications in relation to epigenetic changes such as acetylation and microRNA alterations.

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Novel Approaches for Diagnosing and Management of Cardiovascular Disorders Mediated by Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7096727 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3

Author(s):

Adrian Doroszko ◽

Aneta Radziwon-Balicka ◽

Robert Skomro

Keyword(s):

Oxidative Stress ◽

Cardiovascular Disorders ◽

Novel Approaches

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Efficacy of Composite Extract from Leaves and Fruits of Medicinal Plants Used in Traditional Diabetic Therapy against Oxidative Stress in Alloxan-Induced Diabetic Rats

ISRN Pharmacology ◽

10.1155/2014/608590 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

Brahm Kumar Tiwari ◽

Dileep Kumar ◽

A. B. Abidi ◽

Syed Ibrahim Rizvi

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Diabetic Complications ◽

Small Dose ◽

Diabetic Rats ◽

Vital Role ◽

Special Focus ◽

Wistar Strain ◽

Glucose Plasma

Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on composite extract (CE) and making small dose of naturally occurring antidiabetic plants leaf and fruits. The aim of the present study was to evaluate the beneficial role of CE against alloxan- (ALX-) induced diabetes of Wistar strain rats. A dose-dependent study for CE (25, 50, and 100 mg/kg body weight) was carried out to find the effective dose of the composite compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, plasma advanced oxidation product (AOPP), sialic acid demonstrating disturbed antioxidant status.CE at a dose of 100 mg/kg body weight restored/minimised these alterations towards normal values. In conclusion, small dose of CE possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications.

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Targeting Oxidative Stress in Diabetic Complications: New Insights

Journal of Diabetes Research ◽

10.1155/2018/1909675 ◽

2018 ◽

Vol 2018 ◽

pp. 1-2 ◽

Cited By ~ 2

Author(s):

Hao Wu ◽

Lu Cai ◽

Judy B. de Haan ◽

Robertina Giacconi

Keyword(s):

Oxidative Stress ◽

Diabetic Complications

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Comparative Study of the Antioxidant Effects of Metformin, Glibenclamide, and Repaglinide in Alloxan-Induced Diabetic Rats

Journal of Diabetes Research ◽

10.1155/2016/1635361 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 28

Author(s):

Bonaventure Chukwunonso Obi ◽

Theophine Chinwuba Okoye ◽

Victor Eshu Okpashi ◽

Christiana Nonye Igwe ◽

Edwin Olisah Alumanah

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Diabetic Complications ◽

Significant Proportion ◽

Diabetic Control ◽

Diabetic Rats ◽

Control Group ◽

Diabetic Control Group ◽

Antioxidant Effects ◽

And Oxidative Stress

Diabetes mellitus is one of the serious global health problems affecting a significant proportion of both developed and developing countries. Overproduction of free radicals and oxidative stress has been associated with the development of diabetic complications. In the present study, the antioxidant effects of metformin (MET), glibenclamide (GLI), and repaglinide (REP) were evaluated in alloxan-induced diabetic rats. The findings from this study may possibly help in understanding the efficacy of these standard drugs in managing the complications arising from diabetes mellitus (DM). Alloxan (130 mg/kg BW) was administered as a single dose to induce diabetes. Four (4) groups of rats (n=6) were used; group 1 served as diabetic control while groups 2, 3, and 4 were the diabetic test groups that received MET (25 mg/kg), GLI (2.5 mg/kg), and REP (0.5 mg/kg), respectively. The result of the study showed significant (p<0.05) improvement in the altered antioxidant enzymes (SOD, CAT) and GSH concentration in diabetic treated rats compared with the diabetic control group. MET and REP produced significant effect on the MDA concentration while GLI showed insignificant reduction in the MDA concentration compared with the diabetic control. Findings from this study suggest that the administration of MET, GLI, and REP exerts significant antioxidant effects in alloxan-induced diabetic rats, thus contributing to the protective effect against oxidative stress-induced damage during diabetic complications.

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