Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy

Objective: Great interest is directed to inflammation and oxidative stress involvement in type 2 diabetes pathogenesis. Many researchers suggest they play roles but exactly how is still not clear enough. This encouraged us to investigate relations and potential inter-relationships between them and insulin resistance in type 2 diabetes in its early stage. Whether metformin drug alone, as frequently prescribed, is enough for type 2 diabetes management in this early stage was also an objective.Methods: Blood sugar indices, adiponectin (ADIPOQ), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), nitric oxide (NO), C-reactive protein (CRP), liver and kidney function tests and lipid profile were monitored in non-diabetic volunteers, pre-diabetic and newly diagnosed type 2 diabetic patients before and after metformin drug utilization for 5 mo.Results: MDA, inflammation markers and alanine aminotransferase (ALT) were elevated, and blood sugar indices and lipid profile showed pathological alterations in diabetics compared to non-diabetics; changes were worse in type 2 cases. They were improved to different degrees by metformin treatment except for pancreatic β-cells function and ADIPOQ level showed no significant improvements and it couldn't normalize ALT. Conclusion:Results reflected significant relations and inter-relationships between oxidative stress and inflammation markers in type 2 diabetes in its early stage and indicated that metformin may need to be combined with another drug.

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“…Its level may give information about severity and state of underlying disease process. More production of NO was observed in diabetes [16].…”

Section: Introductionmentioning

confidence: 88%

Malondialdehyde, Adiponectin, Nitric Oxide, C-Reactive Protein, Tumor Necrosis Factor-Alpha and Insulin Resistance Relationships and Inter-Relationships in Type 2 Diabetes Early Stage Is Metformin Alone Adequate in This Stage

Saad

Habib

Refai

et al. 2017

Int J Pharm Pharm Sci

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“…4 Furthermore, reduced glutathione concentration and/or a disproportionate ratio of GSH:GSSG has been associated with a number of diseases, including cancer, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), hepatitis, type 2 diabetes, Parkinson's disease, and cystic fibrosis. 2,[8][9][10][11][12][13][14] Although no experimental research to date has demonstrated disease prevention from GSH supplementation or other strategies to specifically increase GSH, observational research suggests increased dietary glutathione intake has been associated with reduced risk for oral cancer.…”

Section: Introductionmentioning

confidence: 99%

Effects of Oral Glutathione Supplementation on Systemic Oxidative Stress Biomarkers in Human Volunteers

Allen

Bradley

2011

The Journal of Alternative and Complementary Medicine

136

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Background: The tripeptide glutathione (GSH) is the most abundant free radical scavenger synthesized endogenously in humans. Increasing mechanistic, clinical, and epidemiological evidence demonstrates that GSH status is significant in acute and chronic diseases. Despite ease of delivery, little controlled clinical research data exist evaluating the effects of oral GSH supplementation. Objectives: The study objectives were to determine the effect of oral GSH supplementation on biomarkers of systemic oxidative stress in human volunteers. Design: This was a randomized, double-blind, placebo-controlled clinical trial. Setting/location: The study was conducted at Bastyr University Research Institute, Kenmore, WA and the Bastyr Center for Natural Health, Seattle, WA. Subjects: Forty (40) adult volunteers without acute or chronic disease participated in this study. Intervention: Oral GSH supplementation (500 mg twice daily) was given to the volunteers for 4 weeks. Outcome measures: Primary outcome measures included change in creatinine-standardized, urinary F2-isoprostanes (F2-isoP) and urinary 8-hydroxy-2¢-deoxyguanosine (8-OHdG). Changes in erythrocyte GSH concentrations, including total reduced glutathione (GSH), oxidized glutathione (GSSG), and their ratio (GSH:GSSG) were also measured by tandem liquid chromatography/mass spectrometry. Analysis of variance was used to evaluate differences between groups. Results: There were no differences in oxidative stress biomarkers between treatment groups at baseline. Thirtynine (39) participants completed the study per protocol. Changes in creatinine standardized F2-isoP (ng/mg creatinine) (0.0 -0.1 versus 0.0 -0.1, p = 0.38) and 8-OHdG (lg/g creatinine) (-0.2 -3.3 versus 1.0 -3.2, p = 0.27) were nonsignificant between groups at week 4. Total reduced, oxidized, and ratio measures of GSH status were also unchanged. Conclusions: No significant changes were observed in biomarkers of oxidative stress, including glutathione status, in this clinical trial of oral glutathione supplementation in healthy adults.

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“…Increased activity of aldolase reductase pathway in patients with DN consumes NADPH, resulting in impaired the activity of GR. Thus, decreased GPx antioxidant enzyme was seen in patients with DN [33]. A several authors reported a decreased activity of GPx in DN patients [2,34].…”

Section: Nagarajrao and Alharbimentioning

confidence: 96%

Relationship Between Oxidant and Antioxidant Enzymes Status in Type 2 Diabetic Patients With Nephropathy in Saudi Population.

Nagarajrao

Alharbi

2018

Asian J Pharm Clin Res

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Objective: Oxidative stress has crucial role in pathogenesis of diabetic complications. Diabetic nephropathy (DN) is an important microvascular complication of diabetes and is widely recognized as the most common cause of the end-stage renal disease (ESRD) seen in clinical practice. Chemically, oxidative stress occurs as a result of increased levels of lipid peroxides and free radical intermediates, as well as a decrease in the total antioxidant capacity. This study analyzed the relationships between oxidant and antioxidant markers of DN in patients with type 2 diabetes mellitus (T2DM).Methods: A descriptive study was taken during the period from November 2016 to August 2017. The present study included 53 patients suffering from T2DM without nephropathy and 51 patients T2DM with nephropathy along with 69 age-and sex-matched healthy controls. Various biochemical parameters, antioxidant enzymes, and malondialdehyde (MDA) levels were measured and compared. Results:The glycosylated hemoglobin (HbA1c), urea, creatinine, microalbuminuria, and MDA levels were significantly increased (p<0.001), and antioxidant enzyme activities such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CTL) were significantly decreased (p<0.001) in T2DM with nephropathy patients followed by T2DM without nephropathy and control groups. There were a good negative correlations of HbA1c and GPx (r=−0.79), SOD (r=−0.61) and CTL (r=−0.74) (p≤0.05), whereas there was an excellent positive correlation of MDA concentration (r=0.85, p≤0.05) with HbA1c levels in diabetes with nephropathy. Conclusion:The study illustrated that, in diabetic patients, there is an increased concentration of lipid peroxides which may contribute to decreased levels of cellular antioxidant enzymes, further leading to T2DM with nephropathy. Hence, monitoring of these antioxidant enzymes and microalbuminuria parameters in the early stage of diabetic patients could be vital importance in possible preventing further development of complications. We suggest potential and new multiproperty antioxidants therapy as one of the most important treatment strategies for diabetic patients without nephropathy for the prevention and slowing of diabetic with nephropathy before reaching to ESRD.

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Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy

Cited by 193 publications

References 33 publications

Malondialdehyde, Adiponectin, Nitric Oxide, C-Reactive Protein, Tumor Necrosis Factor-Alpha and Insulin Resistance Relationships and Inter-Relationships in Type 2 Diabetes Early Stage Is Metformin Alone Adequate in This Stage

Malondialdehyde, Adiponectin, Nitric Oxide, C-Reactive Protein, Tumor Necrosis Factor-Alpha and Insulin Resistance Relationships and Inter-Relationships in Type 2 Diabetes Early Stage Is Metformin Alone Adequate in This Stage

Effects of Oral Glutathione Supplementation on Systemic Oxidative Stress Biomarkers in Human Volunteers

Relationship Between Oxidant and Antioxidant Enzymes Status in Type 2 Diabetic Patients With Nephropathy in Saudi Population.

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