Alcohol, Aldehydes, Adducts and Airways

Abstract

Drinking alcohol and smoking cigarettes results in the formation of reactive aldehydes in the lung, which are capable of forming adducts with several proteins and DNA. Acetaldehyde and malondialdehyde are the major aldehydes generated in high levels in the lung of subjects with alcohol use disorder who smoke cigarettes. In addition to the above aldehydes, several other aldehydes like 4-hydroxynonenal, formaldehyde and acrolein are also detected in the lung due to exposure to toxic gases, vapors and chemicals. These aldehydes react with nucleophilic targets in cells such as DNA, lipids and proteins to form both stable and unstable adducts. This adduction may disturb cellular functions as well as damage proteins, nucleic acids and lipids. Among several adducts formed in the lung, malondialdehyde DNA (MDA-DNA) adduct and hybrid malondialdehyde-acetaldehyde (MAA) protein adducts have been shown to initiate several pathological conditions in the lung. MDA-DNA adducts are pre-mutagenic in mammalian cells and induce frame shift and base-pair substitution mutations, whereas MAA protein adducts have been shown to induce inflammation and inhibit wound healing. This review provides an insight into different reactive aldehyde adducts and their role in the pathogenesis of lung disease.

Malondialdehyde epitopes are sterile mediators of hepatic inflammation in hypercholesterolemic mice

“…Data from several laboratories suggest that MDA epitopes are not merely markers of oxidative stress but also proinflammatory triggers in various cell types . Thus, we asked whether MDA epitopes could also mediate or further propagate the inflammatory response in the liver.…”

Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans

“…Chemicals may also exert their genotoxic effects in lymphocytes indirectly via induction of inflammation-generated reactive oxygen species or activation of procarcinogens. [21][22][23][24][25].…”

Malondialdehyde–Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti‐MAA Antibodies

“…Therefore, co-exposure to alcohol and cigarette smoke could result in the accumulation of high concentrations of these aldehydes within the lung. When these aldehydes combine in high concentrations as a result of prolonged exposure to alcohol and cigarette smoke, they form a very stable hybrid protein adduct known as the malondialdehyde-acetaldehyde (MAA) adduct, resulting in increased lung inflammation in animal models (Sapkota and Wyatt, 2015; McCaskill et al, 2011). Nevertheless, MAA adduct has not been quantified or otherwise evaluated in the lungs of humans previously.…”