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(epsilon)-(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 micromol/mL) and achieved a further slight reduction after 6 months of
therapy (19.48 +/- 1.339 micromol/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 micromol/24 h after 3 months and 27.02 +/- 4.13 micromol/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
angiotensin II receptor antagonist with reductions in plasma and urinary
pentosidine, plasma CML, and urinary
isoprostanes levels. The present study supports an antagonistic role of
valsartan in the production of AGEs precursors through the chelation of transition metals and an
antioxidant activity that scavenges
reactive oxygen species. This property of
valsartan may broaden the scope of newly developed pharmacologic inhibitors of advanced glycoxidation.