Molecular Mechanisms of Acrolein Toxicity: Relevance to Human Disease

Abstract

Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies.

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis

“…More specifically, allyl alcohol/acrolein is considered a mitochondrial toxin that leads to cell death (Moghe, 2015). Whether apoptosis or necrosis ensues after acrolein exposure appears to be related to dose and cell type.…”

Glutathione s-transferase p in glucose homeostasis in mice.

“…Accumulation of protein-aldehyde adducts, which can diminish protein function and trigger endoplasmic reticulum (ER) stress [98,137], is a proposed mechanistic link between oxidative stress, inflammation and IR [45,46].…”

Used food oils: physical-chemical indicators of quality degradation

“…Lipid degradation induced by frying process and reuse or during long term or inadequate storage leading to oil rancidity, may occur by contacting (with prooxidants or rancid materials), chemical, enzymatic and microbiological pathways. Oxidation is probably the best known and studied process of degradation (Silva et al, 1998); it is a major economic concern of the industry, as it affects sensory (off flavours, browning, viscosity changes, foam) and nutritional quality of edible oils, with potentially toxic compounds formation (Aladedunye, Przybylski, 2011), like acrolein, ubiquitously present in cooked foods and environment (Moghe et al, 2015). In frying process, oil interacts with air, water and other food components, undergoing a complex chemical process of degradation by chain reactions, which affects the triacylglycerol molecules by hydrolysis and oxidation (Takeoka et al, 1997), the latter through a radical mechanism involving oxygen singlet ( 1 O), resulting into peroxidation (primary oxidation) and subsequently, fission, polymerization, condensation, interesterification, cyclization, etc.…”