Assessment of Dna Strand Breaks and Total Antioxidant Status in Type 2 Diabetic Patients With and Without Complications- A Case-Control Study

Nithya, K.; Isabel, W.; Angeline, T.; As, Priscilla; Asirvatham, AJ

doi:10.22159/ajpcr.2017.v10i4.17020

Cited by 3 publications

(3 citation statements)

References 23 publications

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“…Again, we can refer the previous diabetic microvascular complications to the oxidative damage that happens when the ROS level overpowers defensive mechanisms, leading to a cellular imbalance between pro-and antioxidant factors [32]. Elevated levels of oxidation markers such as 8-oxodG most likely prompt to strand breaks and oxidative base changes; and multiple signaling pathways that may likewise add to the unfavorable impacts of glucotoxicity on cellular functions [33,34].…”

Section: Discussionmentioning

confidence: 99%

Urinary Markers of Oxidative Dna Damage in Type 1 Diabetic Children: Relation to Microvascular Complications

Wakeel¹,

Abou-El-Asrar²,

El-Kassas³

et al. 2017

Asian J Pharm Clin Res

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Objective: Type 1 diabetes mellitus (T1DM) is a widespread metabolic disease, which frequently carries with it a significant impact on human health. Oxidative damage and tissue inflammation have been claimed to be a typical pathogenic component for the progression of diabetic complications. We aim in this study to explore the relation of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) (as a marker of nucleic acid oxidation) to microvascular complications in T1DM.Methods: A case–control study, enrolling 45 T1DM children and an equivalent number of healthy subjects, was performed. Full clinical examination and anthropometric measurement were performed to all subjects. Urinary assessment for 8-oxodG and albumin was done in addition to blood sampling for lipid profile and glycated Hb (HbA1c) assay. Complete ocular examination for assessment of diabetic retinopathy (DR) was also done.Results: Levels of urinary 8-oxodG, serum cholesterol, triglycerides, and low-density lipoprotein in cases were significantly higher than non-diabetics; these levels were likewise higher in uncontrolled T1DM patients in comparison with well-controlled T1DM subjects. Urinary 8-oxodG and HbA1c were significantly higher in diabetic patients with albuminuria and DR compared to patients without complications. Significant positive correlation was found between 8-oxodG with HbA1c (r=0.8, p<0.01), diastolic blood pressure (DBP) (r=0.4, p=0.02), and cholesterol (r=0.4, p=0.05).Conclusion: Urinary 8-oxodG was found to be a reliable marker for assessing oxidative DNA damage in T1DM and can be used in the determination of microvascular complications related to diabetes.

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Section: Discussionmentioning

confidence: 99%

Urinary Markers of Oxidative Dna Damage in Type 1 Diabetic Children: Relation to Microvascular Complications

Wakeel¹,

Abou-El-Asrar²,

El-Kassas³

et al. 2017

Asian J Pharm Clin Res

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“…This may be due to hyperglycemia, which has a direct effect on TAS in T2DM patients. The previous finding also suggests that hyperglycemia contributes to increased oxidative stress and decreased TAS, which would lead to further increase in DNA damage in patients with diabetes and its complications [33].…”

Section: Association Of Mthfr Gene Polymorphism Dna Damage and Tasmentioning

confidence: 91%

Association of MTHFR A1298c Gene Variant, Dna Damage, and Total Antioxidant Status With the Risk of Type 2 Diabetes Mellitus and Its Complications

Nithya

Isabel

Angeline

et al. 2018

Asian J Pharm Clin Res

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Objectives:We have examined the association of methylenetetrahydrofolate reductase (MTHFR) gene A1298C variant, DNA damage, and total antioxidant status (TAS) in patients with type 2 diabetes mellitus (T2DM) with and without complications and in healthy controls.Methods: A total of 300 subjects including 100 patients with complications, 100 patients without complications, and 100 controls were included. TAS was assessed by ferric reducing ability of plasma assay. DNA damage was analyzed in lymphocytes using the comet assay. Polymerase chain reactionrestriction fragment length polymorphism analysis was performed to study the MTHFR A1298C gene polymorphism among the study subjects. Results:The results revealed that the MTHFR 1298 AC+CC genotypes were associated with increased risk (2 fold) for diabetes and its complications. When the effect of DNA damage was analyzed, significant differences between individuals with mutant and normal genotype among the diabetic patients (with and without complications) was observed (p≤0.001). In contrary, no significant difference was found between TAS and 1298 genotypes (AA versus AC+CC) in type 2 diabetic patients (with and without complications), p=0.338. We also found a significant difference between the genotypes of the MTHFR A1298C and DNA damage, TAS in T2DM patients (with and without complications) when compared to controls, p<0.001. Conclusions:Our findings suggest that the MTHFR A1298C gene polymorphism is considered as a risk factor for the development of diabetes and its complications among south Indians. Therefore, increased DNA damage and decreased TAS along with the occurrence of a mutant genotype in an individual with diabetes may be at an increased risk for the development of chronic complications.

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“…Those 6-TG-resistant mutants with both PCR sequences intact are mostly likely to carry point mutations in the gpt structural gene. Loss or alteration of one or both bands suggests more complex chromosomal deletions [27] and/or rearrangements involving gpt [28][29]. fig.…”

Section: Deletion Screening Of As52 Gpt Mutantsmentioning

confidence: 99%

Mutational Specificity of 2, 6-Dimethylaniline With in Vitro Human S9 Metabolic Activation in the GPT Gene of As52 Cells

Moon¹,

Kim²

2018

Int J Pharm Pharm Sci

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Objective: The purpose of the current work was to characterize mechanisms of cytotoxicity and mutagenesis of a potential human bladder carcinogen 2,6-dimethylaniline (2,6-DMA).Methods: Chinese hamster ovary (CHO) AS52 cells were exposed to either human S9 activated 2,6-DMA for 6 h or its N-hydroxylamine and aminophenol metabolites for 1 h in serum-free medium. Cell survival determined by trypan blue exclusion 24 h after treatment, and 6-thioguanineresistant mutants at the xanthine-guanine phosphoribosyltransferase (gpt) gene locus were assessed with doses of which relative survival is 30% or more. Nested PCR-based deletion analysis was also performed.Results: AS52 cells exhibited a dose-dependent increase in cytotoxicity and mutant fraction upon treatment of 2,6-DMA and its metabolites, but showing considerable variation in potency with aminophenol metabolites having the highest potency and parent compound at least; at the highest 2,6-dimethyaminophenol dose (10 μM), the mutant fraction in AS52 cells was 8 fold (13.2×10 -5 ) greater than the spontaneous fraction of 1.62×10 -5 Conclusion:These findings indicate the mutagenicity of 2,6-DMA at the gpt gene, which is mediated through hydroxylamine and aminophenol metabolites, and contribute to the elucidation of mechanisms through which 2,6-DMA may exert its effects in vivo.. Total deletion of the gpt gene sequences was found in 1 (4%) of spontaneous and 2 (6%) of the 6-thioguanine mutants generated by N-hydroxy-2,6-DMA.

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Assessment of Dna Strand Breaks and Total Antioxidant Status in Type 2 Diabetic Patients With and Without Complications- A Case-Control Study

Cited by 3 publications

References 23 publications

Urinary Markers of Oxidative Dna Damage in Type 1 Diabetic Children: Relation to Microvascular Complications

Urinary Markers of Oxidative Dna Damage in Type 1 Diabetic Children: Relation to Microvascular Complications

Association of MTHFR A1298c Gene Variant, Dna Damage, and Total Antioxidant Status With the Risk of Type 2 Diabetes Mellitus and Its Complications

Mutational Specificity of 2, 6-Dimethylaniline With in Vitro Human S9 Metabolic Activation in the GPT Gene of As52 Cells

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