Zinc enhances carnosine inhibitory effect against structural and functional age-related protein alterations in an albumin glycoxidation model

Abstract

Age-related complications including protein alterations seen in diabetes and Alzheimer's disease are a major issue due to their accumulation and deleterious effects. This report aims to investigate the effect of zinc supplementation on the anti-glycoxidation activity of carnosine on the in vitro model of albumin-based protein modification. Besides, the therapeutic effect of this combination was tested through the addition of the molecules in tandem (co-treatment) or post initiation (post-treatment) of the protein modification process. Glycation was induced via the addition of glucose to which carnosine (5mM) alone or with various zinc concentrations (125, 250, and 500μM) were added either at 0h or 24h post-glycation induction. On the other hand, protein oxidation was induced using chloramine T (20mM) and treated in the same way with carnosine and zinc. The different markers of glycation (advanced glycation end products (AGEs), dityrosine, and beta-sheet formation (aggregation)) and oxidation (AOPP, advanced oxidation protein products) were estimated via fluorescence and colorimetric assays. Zinc addition induced a significant enhancement of carnosine activity by reducing albumin modification that outperformed aminoguanidine both in the co- and post-treatment protocols. Zinc demonstrated a supplementary effect in combination with carnosine highlighting its potential in the protection against age-related protein modifications processes such as the ones found in diabetes.