Pathogenesis of diabetic nephropathy, which belongs to most serious microangiopathic complications of diabetes, is still not completely clear. Thromboxan A2 and increased oxidation stress are new factors apparently associated with pathogenesis of diabetic nephropathy. It was the aim of the contribution to verify the participation of thromboxan A2 and oxidation stress in the pathogenesis of diabetic nephropathy, as well as to follow the effects of treatment with vitamin E on its progression. In 19 diabetic subjects with microalbuminemia (MA) (age 55.2 +/- 7.6 years), 10 diabetic subjects with normoalbuminemia (NA) (age 54.4 +/- 6.1 years) and in 10 healthy subjects (age 53.6 +/- 9.4) the authors examined the level of malondialdehyde (MLDA) in serum, metabolites of thromboxan A2 (thromboxan B2-TXB2) and prostacyclin PGI2 (6-keto-PGF1 alpha) in urine by means of an RIA method (Isotop, Hungary). The diabetic patients with microalbuminemia were subsequently administered natural vitamin E (EVIT, Rodisna, FRG) at the daily dose of 1200 IU for the period of four months. After two and four months, respectively, MA, MLDA, TXB2 and 6-keto-PGF1 alpha) were examined. The age of the subjects in the two groups was not significantly different. In diabetic subjects with MA, the authors observed significantly higher MLDA levels in serum than in the control individuals (0.55 +/- 0.26 vs. 0.22 +/- 0.02 mumol/l, P < 0.001) and a significant difference occurred also in TBX2 in urine (134.7 +/- 113.8 vs. 27.7 +/- 10.1 ng/12 h, P < 0.001). Increased levels of TXB2 in urine were already present in diabetic subjects with NA as compared with healthy individuals (69.1 +/- 38.8 vs. 27.7 +/- 10.1 ng/12 h, P < 0.05). The treatment with vitamin E caused a significant decrease of MA (93.8 +/- 45.6 vs. 67.95 +/- 28.4 micrograms/min, P < 0.05), MLDA in serum (0.55 +/- 0.26 vs. 0.32 +/- 0.16 mumol/l, P < 0.001). On the basis of our results it is possible to suppose the role of oxidation stress and increased level of thromboxan A2 in the pathogenesis of diabetic nephropathy. The authors also confirmed that the treatment with vitamin E favorably decreases microalbuminemia, while the nephroprotective effect is apparently mediated not only by the antioxidant action, but also the decrease of thromboxan A2 production.

Keywords: Albuminuria; Antioxidants /therapeutic use/; Diabetic Nephropathies /metabolism/; Disease Progression; Humans; Middle Aged; Oxidative Stress; Vitamin E /therapeutic use/