Unexpected elevation of pentosidine formation in collagen incubated with glucose by low concentrations of the AGE-inhibitor aminoguanidine

Grigorova-Borsos, Anne-Marie; Sternberg, M.

doi:10.1007/s00125-004-1399-2

Cited by 3 publications

(1 citation statement)

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“…There is both chemical and biological precedence for the possibility that antioxidants can paradoxically increase AGE levels. Glycation reactions that are carried out in the presence of antioxidants or aminoguanidine can increase pentosidine and CML formation (19,20). Similarly, salicylates have been shown to increase mitochondrial hydrogen peroxide formation (21), i.e., a mechanism that could explain increased ascorbate oxidation and pentosidine formation.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Salsalate Treatment on Serum Levels of Advanced Glycation End Products in Type 2 Diabetes

et al. 2014

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OBJECTIVESalsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications.RESEARCH DESIGN AND METHODSParticipants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine [measured as furosine]) and AGE levels (glyoxal and methylglyoxal hydroimidazolones [G-1H, MG-1H], carboxymethyllysine [CML], carboxyethyllysine [CEL], pentosidine) were measured in patient serum samples.RESULTSForty-eight weeks of salsalate treatment lowered levels of HbA1c and serum furosine (P < 0.001) and CML compared with placebo. The AGEs CEL and G-1H and MG-1H levels were unchanged, whereas pentosidine levels increased more than twofold (P < 0.001). Among salsalate users, increases in adiponectin levels were associated with lower HbA1c levels during follow-up (P < 0.001). Changes in renal and inflammation factor levels were not associated with changes in levels of early or late glycation factors. Pentosidine level changes were unrelated to changes in levels of renal function, inflammation, or cytokines.CONCLUSIONSSalsalate therapy was associated with a reduction in early but not late glycation end products. There was a paradoxical increase in serum pentosidine levels suggestive of an increase in oxidative stress or decreased clearance of pentosidine precursor.

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Section: Discussionmentioning

confidence: 99%