Glutamine dipeptide supplementation improves clinical responses in patients with diabetic foot syndrome

ABSTRACT The effect of glutamine dipeptide (GDP) supplementation in patients with diabetic foot syndrome was evaluated. A total of 22 patients took part in the study. GDP was supplied in 10 g sachets, and was dissolved in water immediately before use, with ingestion once a day, after lunch or after dinner (20 g/day) over a period of 30 days. Quantification of foot insensitive areas, oxidative stress, blood cytokines, and biochemical, hematological and toxicological parameters was performed before and after GDP supplementation. We observed an increase in blood levels of interferon-&#945; (P=0.023), interferon-&#947; (P=0.038), interleukin-4 (P=0.003), interleukin-6 (P=0.0025), interleukin-7 (P=0.028), interleukin-12 p40 (P=0.017), interleukin-13 (P=0.001), leukocytes (P=0.037), eosinophils (P=0.049), and typical lymphocytes (P<0.001) due to GDP administration. In addition, we observed a reduced number (P=0.048) of insensitive areas on the foot, and reduction (P=0.047) of fasting hyperglycemia. Patients also showed increased blood high density lipoprotein (P<0.01) and protein thiol groups (P=0.004). These favorable results were associated with the absence of renal and hepatic toxicity. These results are of clinical relevance, since supplementation with GDP over 30 days improved clinical responses in patients with diabetic foot syndrome

Arachidonic acid triggers an oxidative burst in leukocytes

The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid- (AA) stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells), Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 µM (up to 16-fold), whereas in rat cells it varied from 10 to 20 µM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by N-ethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems such as xanthine-xanthine oxidase, cytochromes P-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol