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Background: Hyperglycaemia-induced depletion of reduced glutathione (GSH) causes erythrocyte oxidative stress (EOS), which leads to vascular events including exacerbation of thrombotic events evidenced by changes in D-dimer level. It would, therefore, appear that there is a complex link between GSH and D-dimer, which are part of an emerging array of biomarkers associated with diabetes. The objective of this study was to investigate evidence of correlation between levels of plasma D-dimer and erythrocyte GSH in diabetes disease progression. Subjects and methods: A cohort of 69 subjects were selected based on medical history plus clinical findings and equally divided into control, prediabetes and diabetes groups, matched for age and sex. Plasma D-dimer and erythrocyte reduced glutathione (GSH) were determined and separated into quartiles as a means of indicating disease severity. Statistical analysis was by Pearson's correlation coefficient. Results: Of the three groups, only the diabetes group showed any correlation between GSH and D-dimer. Of importance is that for increasing GSH, the second quartile range of GSH (x ± SD = 45 ± 22 mg/100ml) showed a statistically significant negative correlation for ranked D-dimer (x ± SD = 1055 ± 828 μg/l; r = -0.88; P < 0.02). The fourth quartile GSH range (x ± SD = 79 ± 40 mg/100 ml) showed a statistically significant positive correlation with D-dimer (x ± SD = 1055 ± 828 μg/l; r = 0.91; P < 0.02). Thus, within the diabetes group only, the increasing level of oxidative stress as measured by GSH first indicates a reduction in D-dimer followed by a rise in D-dimer, which led to the proposal of a two-part process of atherosclerosis that reconciles previous contradictory findings. Conclusions: This study provides not only evidence of a correlation between oxidative stress level and fibrinolysis in diabetes, but also an explanation of why previous studies have found both hypoor hyperfibrinolysis associated with diabetes. [ABSTRACT FROM AUTHOR]

Summary: In studies of vitamin E effectiveness in diabetes, there are still controversies surrounding negative observational and positive experimental results. However, there is no controversy that antioxidant vitamin E is regenerated from its pro-oxidant tocopheroxyl radical by a network of interacting co-antioxidants. The network of interacting co-antioxidants has only been studied individually. The hypothesis we propose is that a vitamin E regeneration system (VERS) model based on the complex interactions of the co-antioxidants provides a rationale for vitamin E supplementation as a therapeutic adjunct in diabetes. Furthermore, the factors considered prior to the use of Vitamin E as a supplement in diabetes research and therapy, the effectiveness of vitamin E supplementation and the limitations have been identified in the literature. There is no single study of vitamin E supplementation or efficacy that has determined vitamin E levels in combination with all of the co-antioxidants that interact to regenerate oxidised vitamin E. Therefore, there is a lack of good evidence for or against vitamin E being unilaterally depleted in the antioxidant network. There is also lack of rationale for choice of co-antioxidant supplementation. In essence, the normal conditions for effective antioxidant activity of vitamin E supplementation have yet to be fully explored. We propose a coherent model of VERS, and recommend that VERS status needs to be assessed, as part of evidence-based clinical practice to determine whether vitamin E should be recommended for the diabetic patient. We also propose an algorithm, based on the antioxidant activity and confounding factors, to guide the formulation of a credible hypothesis for clinical trials in assessing the function of vitamin E and treatment outcomes. The proposed model hinges on pertinent questions that have to be addressed to avoid organising a clinical trial that has been identified as biased. [Copyright &y& Elsevier]

This study aims to evaluate the significance of the changes of erythrocyte reduced glutathione (GSH) in the course of diabetes mellitus including the pre-diabetes stage and cardiovascular disease co-morbidity. A total of 222 participants (female:male, 107:115) were selected and their erythrocyte GSH levels were measured. The participants were divided into four groups: (i) control; (ii) those with blood glucose level ≥5.6 mmol/l but < 6.9 mmol/l as pre-diabetes mellitus with no other pathology; (iii) diabetes without co-morbidity; and (iv) those with diabetes mellitus and cardiovascular disease. Statistical analysis was by ANOVA followed by a Fisher's LSD post hoc test. We observed that GSH concentration was significantly different between groups (P < 0.04). The Fisher's post hoc test indicated significant differences in erythrocyte GSH levels between the pre-diabetes mellitus and diabetes mellitus groups compared to control (P < 0.005 and P < 0.05, respectively). A statistically significant change (P < 0.001) involving an initial fall followed by a rise in erythrocyte GSH levels was observed when diabetes mellitus and diabetes mellitus+cardiovascular disease groups were combined and assessed with respect to period of diabetes. We conclude that oxidative stress is already present in the pre-diabetes stage as determined by the fall in GSH, representing the initial phase of oxidative stress in diabetes mellitus progression. This finding provides evidence that antioxidant markers such as GSH could be a useful tool for pre-diabetes mellitus screening. [ABSTRACT FROM AUTHOR]

Phragmites karka (Retz.) of family Poaceae is a pristine tropical plant that is well known to the local healers for ailments of diabetes, fever, diarrhea and CNS depression but lacks the scientific evidence behind its traditional usage. Hence, we explicated this plant to find the scientific basis of its traditional utilization. The current study aims to find out the antidiabetic potential, toxicity after oral administration and in vitro cytotoxic activity of aerial parts of the plant on HeLa cells. The plant was extracted with methanol by maceration and the crude extract was then subjected to solvent partitioning with modified Kupchan method for preparing several fractions. Phytochemical screening and total phenolic content of the plant was first determined through established procedures. Acute toxicity of the plant was studied by orally administering a single high dose (5000 mg/kg) of drug. Cytotoxicity of the methanolic plant extract was determined by measuring the percentage of cell viability on human cervical cancer cell lines, HeLa. In vitro antidiabetic activity was determined through iodine starch and DNSA (3,5-dinitrosalicylic acid) method of α-amylase inhibition. Finally, in vivo oral glucose tolerance test and alloxan induced antidiabetic activity test was performed at 150 and 300 mg/kg body weight doses of plant extract to confirm the in vivo antidiabetic activity. No mortality was demonstrated by Phragmites karka in the acute toxicity test. However, signs of cellular toxicity was observed and histopathological studies on major organs exhibited necrosis in liver and kidney. In vitro cytotoxicity assay revealed the death of HeLa cells by DCM (dichloromethane) and n-hexane fractions of plant extract at 100 and 10 μg/mL concentrations. The IC 50 value of the fractions were later evaluated by MTT assay (316.1 and 96.7 μg/mL for n-hexane and DCM fractions, respectively). In the iodine starch and DNSA method of α-amylase enzyme inhibitory activity test, substantial inhibition of enzyme was observed with the IC 50 values of 2.05 and 2.08 mg/mL, respectively. In the in vivo antidiabetic activity test, considerable reduction in blood glucose level of diabetic mice was detected in both oral glucose tolerance test and alloxan induced antidiabetic activity test. In addition, the microscopic examination of pancreas showed noticeable recovery of pancreatic β cells and the blood lipid profile analysis represented a significant (p < 0.05) reduction of total cholesterol, LDL (low density lipoprotein) and triglyceride level in plant extract treated mice. Results of this study reveals that the Phragmites karka extract is toxic at cellular level after oral administration and cytotoxic when tested on HeLa cells. The plant also evidenced hypoglycemic property, possibly through the inhibition of α-amylase enzyme and recovered the pancreatic beta cells along with the improvement of lipid profile of diabetic mice. However, robust studies on this plant is required to isolate the bioactive compounds, elucidate structures and evaluate their mechanism of actions in support of our findings. Toxicology and Safety, Quality Traditional Medicine. Image 1 [ABSTRACT FROM AUTHOR]