TY - JOUR
T1 - Effect of Irbesartan treatment on plasma and urinary markers of protein damage in patients with type 2 diabetes and microalbuminuria
AU - Rabbani, Naila
AU - Adaikalakoteswari, Antonysunil
AU - Rossing, Kasper
AU - Rossing, Peter
AU - Tarnow, Lise
AU - Parving, Hans Henrik
AU - Thornalley, Paul J.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - The aim of this study was to assess the effect of the angiotensin II receptor blocker Irbesartan on protein damage by glycation, oxidation and nitration in patients with type 2 diabetes and microalbuminuria. In a doublemasked randomised crossover trial of 52 hypertensive type 2 diabetic patients, antihypertensive treatment was replaced with bendroflumethiazide. After 2-months washout, patients were treated randomly with Irbesartan 300, 600, and 900 mg o.d., each dose for 2 months in a threeway crossover study. Glycation, oxidation and nitration adduct residues in plasma protein and related urinary free adducts were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Treatment with Irbesartan decreased urinary excretion of advanced glycation endproducts (AGEs)-methylglyoxaland glyoxal-derived hydroimidazolones, MG-H1 and G-H1. Urinary AGEs were decreased by 30-32%. In plasma protein, treatment with Irbesartan increased content of glycation adducts N ε-fructosyl- lysine, AGEs N ε-carboxymethyl- lysine, N ε- carboxyethyl-lysine and pentosidine, and also increased content of oxidation markers N-formylkynurenine and dityrosine. This was attributed to decreased clearance of plasma protein modified by Ne-fructosyl-lysine and oxidative markers through the glomerular filter tightened by Irbesartan treatment. Treatment of patients with type 2 diabetes with Irbesartan decreased urinary excretion of MG-H1, G-H1 and 3-NT, which may result from decreased exposure to these AGEs. This is likely achieved by blocking angiotensin II signalling and related down-regulation of glyoxalase 1 and may contribute to health benefits of Irbesartan therapy.
AB - The aim of this study was to assess the effect of the angiotensin II receptor blocker Irbesartan on protein damage by glycation, oxidation and nitration in patients with type 2 diabetes and microalbuminuria. In a doublemasked randomised crossover trial of 52 hypertensive type 2 diabetic patients, antihypertensive treatment was replaced with bendroflumethiazide. After 2-months washout, patients were treated randomly with Irbesartan 300, 600, and 900 mg o.d., each dose for 2 months in a threeway crossover study. Glycation, oxidation and nitration adduct residues in plasma protein and related urinary free adducts were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Treatment with Irbesartan decreased urinary excretion of advanced glycation endproducts (AGEs)-methylglyoxaland glyoxal-derived hydroimidazolones, MG-H1 and G-H1. Urinary AGEs were decreased by 30-32%. In plasma protein, treatment with Irbesartan increased content of glycation adducts N ε-fructosyl- lysine, AGEs N ε-carboxymethyl- lysine, N ε- carboxyethyl-lysine and pentosidine, and also increased content of oxidation markers N-formylkynurenine and dityrosine. This was attributed to decreased clearance of plasma protein modified by Ne-fructosyl-lysine and oxidative markers through the glomerular filter tightened by Irbesartan treatment. Treatment of patients with type 2 diabetes with Irbesartan decreased urinary excretion of MG-H1, G-H1 and 3-NT, which may result from decreased exposure to these AGEs. This is likely achieved by blocking angiotensin II signalling and related down-regulation of glyoxalase 1 and may contribute to health benefits of Irbesartan therapy.
KW - Angiotensin receptor blocker
KW - Diabetic nephropathy
KW - Glycation
KW - Glycosylation gap
KW - Methylglyoxal
KW - Microalbuminuria
KW - Nitrotyrosine
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84862775521&partnerID=8YFLogxK
U2 - 10.1007/s00726-011-0857-7
DO - 10.1007/s00726-011-0857-7
M3 - Article
C2 - 21384133
AN - SCOPUS:84862775521
SN - 0939-4451
VL - 42
SP - 1627
EP - 1639
JO - Amino Acids
JF - Amino Acids
IS - 5
ER -