Effects of valsartan therapy on protein glycoxidation

Several lines of evidence suggest that both advanced glycation end products (AGEs) and oxidation processes play key roles in the physiology of aging and age-related pathologies, leading to irreversible proteins modifications in both tissues and the extracellular matrix. Such an accelerated accumulation of these modifications has been reported to be present in several age-related chronic diseases, such as atherosclerosis, diabetes, arthritis, and neurodegenerative diseases. The current literature reveals that the specific inhibition of AGEs may constitute an innovative therapeutic goal. In experimental animals, the use of sartans significantly reduces blood pressure and kidney pentosidine content, improving both histologic renal damage and proteinuria. In this study, 12 subjects who were affected by diabetes mellitus and hypertension were subjected to oral antihypertensive therapy with valsartan (class of sartans) with timed sampling of plasma and urine pentosidine, N ε -(carboxymethyl)lysine (CML), malondialdehyde, and isoprostanes levels, respectively, at baseline and after both 3 and 6 months, with parallel ongoing evaluation of glycemic control and blood pressure levels. Valsartan elicited a good antihypertensive effect with a 30% decrease in plasma pentosidine levels ( P < .05) after 3 months of therapy, followed by a slight increase after 6 months. Urinary pentosidine concentrations exhibited a 40% decrease after 3 months (215 ± 19 vs 129 ± 23 nmol/24 h) and a further significant reduction after 6 months of therapy (105 ± 24 nmol/24 h). Plasma CML levels showed a progressive decrease after 3 months (23.15 ± 3.215 vs 19.88 ± 1.684 μmol/mL) and achieved a further slight reduction after 6 months of therapy (19.48 ± 1.339 μmol/mL); for urinary CML, a statistically significant reduction was gained after the sixth month of therapy (48.51 ± 5.70 vs 30.30 ± 2.77 μmol/24 h after 3 months and 27.02 ± 4.13 μmol/24 h after 6 months; F = 7.62, P < .005). Plasma and urinary concentrations of malondialdehyde were slightly modified by valsartan treatment; the mean levels after both 3 and 6 months did not significantly differ from baseline. Urinary 15-F2t-isoprostanes (2.96 ± 0.45 ng/24 h) levels displayed a progressive decrease after both 3 (2.27 ± 0.31 ng/24 h) and 6 months (1.70 ± 0.23 ng/24 h) with statistical significance achieved only at the end of the study ( P < .05). The present data suggest interesting in vivo antiglycation and antioxidation effects of this