Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation

Abstract

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of diff erent oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by diff erent mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving diff erent aspects of research which are essentially focused on setup and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in diff erent pathophysiological conditions; (2) to elucidate the molecular basis of their biological eff ects; and (3) to discover compounds able to inhibit AGEs/ ALEs damaging eff ects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving diff erent precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.

The Mechanisms of Inhibition of Advanced Glycation End Products Formation through Polyphenols in Hyperglycemic Condition

“…AGEs exert their damaging effects on cell functions through several mechanisms such as production of free radicals, fragmentation of protein or lipid, altering enzyme activity, modifying immunogenicity, oxidation of nucleic acids or lipids, carbonyl stress or interaction with AGEs receptors on the cell surface [10]. The AGEs are capable of forming an AGE-receptor complex by binding to specific or non-specific receptors such as AGE-R1 (P60/OST-48 protein), AGE-R2 (80 K-H phosphoprotein), AGE-R3 (galectin), and AGE-RAGE [11][12][13]. Among different receptors RAGE as a multi-ligand receptor of the immunoglobulin superfamily, plays a distinguished role in the onset of AGEs induced metabolic disorders (l " Fig.…”

“…Indeed some AGEs or ALEs adducts have the same molecular structure. For example a reaction of glyoxal with lysine residues produces CML, which is considered as an ALE or AGE compound [13]. Plant phenolic compounds such as punicalagin, ellagic acid, anthocyanins, oleanolic acid, ursolic acid, or gallic acid, which can all be found in pomegranate [92] have shown a lipid oxidation inhibitory activity by scavenging free radicals [93].…”

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

“…Protein carbonyls are chemically stable and easy to detect after modification with dinitrophenylhydrazine by various methods of immunostaining; for example, immunoblot, ELISA, and fluorescence microscopy [for a review, see Ref. (154)]. …”

Albumin Cys34 adducted by acrolein as a marker of oxidative stress in ischemia-reperfusion injury during hepatectomy

“…Among the different mechanisms of oxidative stress involved in the I/R damage, those involving the formation of reactive carbonyl species (RCSs), such as lipid peroxidation products, are gaining great interest [12]. RCSs are strongly electrophilic towards endogenous nucleophilic substrates, such as DNA and proteins, and lead to irreversible covalent modifications [13]. Miyata and colleagues have defined ''carbonyl stress'' as the accumulation in the plasma of RCSs derived from lipid, carbohydrate and protein carbonylation [14].…”

“…For this reason, RCSs are not only direct cytotoxic but can also mediate and propagate oxidative stress and tissue damage as second messengers. RCSs from lipid peroxidation cascade are quite heterogeneous and can be divided into three main classes, namely: (1) the a,b-unsaturated aldehydes, including 4-hydroxy-2-nonenal (HNE) and acrolein (ACR); (2) di-aldehydes, including the well-known lipid peroxidation by product malondialdehyde and glyoxal; (3) keto-aldehydes, such as methylglyoxal [13]. Several studies, both in animal models and in humans, have reported the increase of RCSs such as free aldehydes or protein adducts in the liver under I/R damage [15][16][17][18][19].…”