Paradoxical impact of antioxidants on post-Amadori glycoxidation: Counterintuitive increase in the yields of pentosidine and Nepsilon-carboxymethyllysine using a novel multifunctional pyridoxamine derivative.

The inhibition of post-Amadori advanced glycation end product (AGE) formation by three different classes of AGE inhibitors, carbonyl group traps, chelators, and radical-trapping antioxidants, challenge the current paradigms that: 1) AGE inhibitors will not increase the formation of any AGE product, 2) transition metal ions are required for oxidative formation of AGE, and 3) screening AGE inhibitors only in systems containing transition metal ions represents a valid estimate of potential in vivo mechanisms. This work also introduces a novel multifunctional AGE inhibitor, 6-dimethylaminopyridoxamine (dmaPM), designed to function as a combined carbonyl trap, metal ion chelator, and radical-trapping antioxidant. Other AGE inhibitors including pyridoxamine, aminoguanidine, o-phenylenediamine, dipyridoxylamine, and diethylenetriaminepentaacetic acid were also examined.

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.

[structure: see text] Pyridoxamine is known to be an effective inhibitor of both advanced glycation (AGE) and advanced lipoxidation (ALE) end products. The synthesis of a novel multifunctional AGE and ALE inhibitor, 6-dimethylaminopyridoxamine (dmaPM, 11) is described. The 6-dimethylamino substituent increases the radical trapping ability of pyridoxamine's phenolic group.

Determination of the alpha-tocopherol inhibition rate constant for peroxidation in low-density lipoprotein.

This work reports an estimate of the inhibition rate constant (k(inh)) for alpha-tocopherol (alpha-TOH) in low-density lipoproteins (LDL) based on cholesteryl linoleate hydroperoxide products formed during autoxidation of intact lipoproteins. The ratio of cis,trans/trans,trans product hydroperoxides was determined during the consumption of the antioxidant. For a reasonable determination of k(inh) in LDL, the pro-oxidant behavior of alpha-TOH was minimized by oxidizing LDL with an unsymmetrical amphiphilic azo initiator which significantly reduces phase-transfer mediated pro-oxidant effects of alpha-TOH.