L-arginine metabolism in patients with diabetes mellitus with diabetic polyneuropathy and foot ulcers

The purpose of the study was to investigate the effect of L-arginine metabolism on the development and healing of ulcerative foot defects in patients with diabetes mellitus (DM) concurrent with polyneuropathy of the diabetic foot syndrome.

Seventy patients were examined. These included 25 patients with DM and clinical signs of diabetic polyneuropathy (Group 1), 25 patients with DM and neuropathic ulcerative foot defects (Group 2), and 20 healthy individuals (a control group). High performance liquid chromatography was used to determine plasma nitrites and nitrates. To study the activity of enzymes controlling L-arginine conversion, biopsy was performed from the skin of the dorsum of the foot in control individuals and Group 1 patients and from a portion of the skin from the edges of ulcerative defect and from granulation tissue in Group 2 patients. The activity (inducible and endothelial) of NO syntheses was regarded as the capacity of tissue enzymes to convert 3H-L-arginine into 3H-L-citrullin. The activity of arginase in the biopsy specimens was determined by its ability to convert L-arginine into urea. The concentration of transforming growth factor-/}/ (TGF-B/ was measured by using a BIOTRAK kit (Amersham, UK) after special pretreatment of the specimens. In Group 2 patients, the plasma level of NO was more than twice higher than that in the control group and almost 4 times than that in Group 1 [79.68 (55.41; 95.08), 39.03 (28.04; 41.32), and 20.98 (13.46; 29.79) pmol/l, respectively; p < 0.05]. There was a marked expression of iNO-synthase in the biopsy specimens from patients with trophic ulcers as compared with the controls and in patients without ulcerative defects [5.92 (4.63; 7.97), 3.36 (2.71; 3.9), and 1.59(1.05; 2.74) V/T/mgof protein, respectively; p < 0.05]. There was a reduction in the activity of eNO-synthase in the biopsy specimens from patients with peripheral neuropathy as compared with the controls and in patients without ulcerative defects of foot defects [1.22 (1.04; 2.14), 3.41 (2.36; 4.07), and 3.17(2.9; 4.34) V/T/mg protein, respectively; p < 0.05]. The content of arginase in the skin and granulation tissue biopsy specimens taken from the edge of ulcerative defects was much higher than that in the control group and its level in patients without ulcers did not dijfer from that in healthy individuals [1.96 (1.63; 2.65), 0.28 (0.14; 0.37), and 0.52 (0.35; 0.59) pg/mg of protein, respectively; p < 0.05]. A rather low concentration ofTGF-p, was found in the tissues of DM patients with trophic ulcers than in the control group [0.88 (0.58; 1.33) ng/mg of protein versus 2.48 (2.21; 3.17) ng/mg of protein, p < 0.01].

Thus, metabolism of the amino acid L-arginine and its regulation, TGF-/3, in particular, play an important role during wound healing.

nitric oxide, nitric oxide synthase, transforming growth factor B-1, diabetic foot syndrome

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