Table 2 Summary of the biological connections of AGE–alcohol–adducts with alcohol-mediated tissue injury.

Brain

AGE-albumin adducts

↑ RAGE overexpression

↑ MAPK (JNK and p38K), Bax, and microglial activation

↑ neuronal inflammation, apoptosis, and damage^{108,111,119,202}

Ethanol

↑ RAGE expression

↑ ROS, Nrf2, GFAP, Iba1, lipid peroxidation, HMGB1,

TLR-4, neuroimmune markers,

↑ CYP2E1, oxidative stress, and inflammation

↑ neuroinflammation, neuronal apoptosis, and memory Impairment^203,204

AA-protein adducts:

AA-tubulin adducts

AA-DA adducts (salsolinol)

↓ microtubule formation

↑ dysfunction of cytoskeletal components of nerve cells

↑ neurotoxin involved in the pathogenesis of AUD and PD

↑ neuronal damage and degeneration^{189,190,191,192,193,194,195,196,197,198}

AA-DNA adducts

↓ DNA integrity and neuronal viability

↓ represses DNA repair enzymes/system

↑ genetic instability and DNA mutations

↑ correlated with AUD^{53,192,197,198}

AA-AGE adducts

↑ ROS and oxidative stress

↑ neurotoxicity, neuronal apoptosis, and degeneration in a dose-dependent manner¹⁹⁹

Liver

AGE production

plasma AGEs

AGE-protein adducts

↓ decrease in albumin turnover in plasma

↑ aggregation of adduct proteins

↑ activation of Kupffer and HSCs

↑ death of hepatocytes^232,233

AA adducts

MDA adducts

MAA adducts

4-HNE adducts

HER adducts

Ethanol

↑ TNF-α, IL-12, IL-18, MIF, PDGF

↑ stimulate the transformation of the HSCs

↑ activate myofibroblasts

↑ activates infiltration of neutrophils into the liver↓ ALDH2 function^{214,215,216,217,218,219,220,221,222,223,224,225,226,227,228,229,230}

↑ CYP2E1, oxidative stress, AFLD, and advanced ALD^{203,204,205,206,207,208,209,210,211,212,213}

AA-AGE adducts

↑ RAGE expression

↑ ROS and oxidative stress

↑ hepatic fatty degeneration and steatosis

↑ hepatocyte ballooning, apoptosis, and steatosis

↑ ALD and AFLD^215,231

Lung

soluble RAGE (+HMGB1)

↑ lung inflammation^239,240

MDA adducts

4-HNE adducts

↑ oxidative stress

↑ pulmonary dysfunction

↑ lung epithelial barrier dysfunction

↑ acute respiratory distress syndrome (ARDS)^164,234

MAA adducts

↓ impedes the wound healing process

↑ inflammatory processes, PKC-mediated release of IL-8

↑ correlated with AUD^{179,235,236,237,238}

Heart

MDA adducts

4-HNE adducts

↓ ALDH2 function

↑ oxidative stress

↑ cardiac dysfunction^{241,242,243,244}

Gut

AA-adducts

AA-MDA adducts

↑ oxidative stress

↑ leaky gut with increased intestinal cell permeability and endotoxemia^{137,181,245,246,247,248,249,250}

Pancreas

4-HNE adducts

HER adducts

↑ pancreatitis, β-cell apoptosis^{251,252,253,254,255}

Erythrocytes

AA adducts

↑ correlated with FASD^257,258

Testis

RAGE overexpression

↑ oxidative stress and inflammation↑ testis dysfunction and degeneration^{253,259,260,261}