Attenuation of Glucose-Induced Myoglobin Glycation and the Formation of Advanced Glycation End Products (AGEs) by (R)-α-Lipoic Acid In Vitro

Abstract

High-carbohydrate containing diets have become a precursor to glucose-mediated protein glycation which has been linked to an increase in diabetic and cardiovascular complications. The aim of the present study was to evaluate the protective effect of (R)-α-lipoic acid (ALA) against glucose-induced myoglobin glycation and the formation of advanced glycation end products (AGEs) in vitro. Methods: The effect of ALA on myoglobin glycation was determined via the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The extent of glycation-induced myoglobin oxidation was measured via the levels of protein carbonyl and thiol. Results: The results showed that the co-incubation of ALA (1, 2 and 4 mM) with myoglobin (1 mg/mL) and glucose (1 M) significantly decreased the levels of fructosamine, which is directly associated with the decrease in the formation of AGEs. Furthermore, ALA significantly reduced the release of free iron from myoglobin which is attributed to the protection of myoglobin from glucose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin from oxidative damage, as seen from the decreased protein carbonyls and increased protein thiols. Conclusion: The anti-glycation properties of ALA suggest that ALA supplementation may be beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

Fructose and methylglyoxal-induced glycation alters structural and functional properties of salivary proteins, albumin and lysozyme

“…Whereas for saliva only MGO reduced thiol content, indicating association between glycation products and oxidative state of proteins. Studies corroborate these results showing that glycation process provoked a reduction in free thiol group of proteins [83,103,104]. Moreover, Rajeshwari et al [105] found decreased levels of thiols in saliva of diabetic group in relation to healthy individuals.…”

Ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats

“…These findings correlate with the results of other studies where oxidative stress was induced in the testes of rats and all these parameters were reduced ( Fan et al, 2020 , Nna et al, 2019 ). In other studies reported, reduction in antioxidant enzymes and oxidative stress was associated with protein glycation ( Dzięgielewska-Gęsiak et al, 2019 , Ghelani et al, 2018 ). Protein glycation was reported to cause the inactivation of antioxidant enzymes due to the alteration of amino acids present in the active sites of these antioxidant enzymes ( Tavares et al, 2019 ).…”

The Antioxidant and Pro-oxidant Impacts of Varying Levels of Alpha-Lipoic Acid on Biomarkers of Myoglobin Oxidation in Vitro

“…Although the impact of R-ALA on human proteins has been formerly tested counting the oxidative-mediated damage, a wide range of experimental ALA doses were used among former in vitro and in vivo studies, the majority of these doses were high enough to be far from physiological relevant conditions (Suzuki et al, 1992(Suzuki et al, & 2017Ghelani et al, 2018). The ability of R-ALA at a low level (50-100 µM) as those implemented in the present research to inhibit protein oxidative damage has merely been assessed in the literature.…”

“…Thereby, it is a critical factor affecting the redox reaction cascade in the cardiac muscle, which helps metabolic and functional protection of the heart from oxidative damage (Wittenberg, 2009;Hendgen-Cotta et al, 2014;Serra et al, 2018). Because of its high susceptibility to oxidative changes, human myoglobin has been considered as one of the main physiological targets for many in vitro studies of oxidative damage (Roy et al, 2004(Roy et al, & 2010Ghelani et al, 2018). R-alpha-lipoic acid (R-ALA) is the naturally occurring biologically active dithiol found in foods of animal origin (Shay et al, 2009).…”