Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage

被引:147
作者
Voziyan, PA [1 ]
Hudson, BG [1 ]
机构
[1] Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN 37232 USA
关键词
pyridoxamine; AGE; reactive oxygen species; reactive carbonyl compounds; diabetes; kidney stones; atherosclerosis; ageing;
D O I
10.1007/s00018-005-5082-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The discovery that pyridoxamine (PM) can inhibit glycation reactions and the formation of advanced glycation end products (AGEs) stimulated new interest in this B-6 vitamer as a prospective pharmacological agent for treatment of complications of diabetes. The mechanism of action of PM includes: (i) inhibition of AGE formation by blocking oxidative degradation of the Amadori intermediate of the Maillard reaction; (ii) scavenging of toxic carbonyl products of glucose and lipid degradation; and (iii) trapping of reactive oxygen species. The combination of these multiple activities along with PM safety posture it as a promising drug candidate for treatment of diabetic complications as well as other multifactorial chronic conditions in which oxidative reactions and carbonyl compounds confer pathogenicity.
引用
收藏
页码:1671 / 1681
页数:11
相关论文
共 102 条
[21]   Pyridoxamine lowers kidney crystals in experimental hyperoxaluria: A potential therapy for primary hyperoxaluria [J].
Chetyrkin, SV ;
Kim, D ;
Belmont, JM ;
Scheinman, JI ;
Hudson, BG ;
Voziyan, PA .
KIDNEY INTERNATIONAL, 2005, 67 (01) :53-60
[22]  
Cohen PP, 1940, J BIOL CHEM, V136, P565
[23]   GLYCATION - A PATHOLOGICAL MODIFICATION IN NEUROPATHIES - A HYPOTHESIS [J].
COLACO, CALS ;
HARRINGTON, CR .
NEUROREPORT, 1994, 5 (08) :859-861
[24]   Paradoxical impact of antioxidants on post-Amadori glycoxidation -: Counterintuitive increase in the yields of pentosidine and Nε-carboxymethyllysine using a novel multifunctional pyridoxamine derivative [J].
Culbertson, SM ;
Vassilenko, EI ;
Morrison, LD ;
Ingold, KU .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (40) :38384-38394
[25]   Synthesis of a novel radical trapping and carbonyl group trapping anti-AGE agent: A pyridoxamine analogue for inhibiting advanced glycation (AGE) and lipoxidation (ALE) end products [J].
Culbertson, SM ;
Enright, GD ;
Ingold, KU .
ORGANIC LETTERS, 2003, 5 (15) :2659-2662
[26]   Chlorination of pyridinium compounds -: Possible role of hypochlorite, N-chloramines, and chlorine in the oxidation of pyridinoline cross-links of articular cartilage collagen type II during acute inflammation [J].
Daumer, KM ;
Khan, AU ;
Steinbeck, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (44) :34681-34692
[27]  
DAWSON RMC, 1986, DATA BIOMEDICAL RES, P412
[28]   Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat [J].
Degenhardt, TP ;
Alderson, NL ;
Arrington, DD ;
Beattie, RJ ;
Basgen, JM ;
Steffes, MW ;
Thorpe, SR ;
Baynes, JW .
KIDNEY INTERNATIONAL, 2002, 61 (03) :939-950
[29]  
Degenhardt TR, 2002, J AM SOC NEPHROL, V13, p652A
[30]   AGES in brain ageing:: AGE-inhibitors as neuroprotective and anti-dementia drugs? [J].
Dukic-Stefanovic, S ;
Schinzel, R ;
Riederer, P ;
Münch, G .
BIOGERONTOLOGY, 2001, 2 (01) :19-34