. 2021 Feb 10;53(2):168–188. doi: 10.1038/s12276-021-00561-7

Table 2.

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

Cells/organs	AGE–alcohol–adducts	Consequences
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^189–198
	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^214–230 ↑ CYP2E1, oxidative stress, AFLD, and advanced ALD^203–213
	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^{179,235–238}
Heart	MDA adducts 4-HNE adducts	↓ ALDH2 function ↑ oxidative stress ↑ cardiac dysfunction^241–244
Gut	AA-adducts AA-MDA adducts	↑ oxidative stress ↑ leaky gut with increased intestinal cell permeability and endotoxemia^{137,181,245–250}
Pancreas	4-HNE adducts HER adducts	↑ pancreatitis, β-cell apoptosis^251–255
Erythrocytes	AA adducts	↑ correlated with FASD^257,258
Testis	RAGE overexpression	↑ oxidative stress and inflammation↑ testis dysfunction and degeneration^{253,259–261}

↑ increase/activate, ↓ decrease/inactivate.