Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant whose potential as a serious environmental health threat is beginning to be recognized. In addition to endogenous production (metabolism and lipid peroxidation), humans are exposed to acrolein through oral (food and water), respiratory (cigarette smoke, vehicle exhaust, and use of fungicides) and dermal routes. Acrolein has been shown to play a role in a variety of disease states, including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes, and neurological, hepatic, and renal toxicity. At the cellular level, acrolein exposure has multiple toxic effects, including DNA and protein uptake, 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, focusing on known and expected contributions to clinical disease, as well as potential therapeutic approaches. Acrolein (CAS number 107-02-8) has been investigated Listed by the Department of Homeland Security (DHS), the Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA) as a high priority toxic chemical (Acrolein Toxicology Fact Sheet, 2007) Recommendations are made for exposure levels to acrolein in food and water. Acrolein is an industrial chemical and biocide with more than 500 million pounds of acrolein produced annually in the United States (Acrolein Toxicological Facts, 2007). The past decade has witnessed a dramatic increase in research on acrolein, and this review attempts to assimilate this growing literature, focusing on the molecular mechanisms underlying acrolein toxicity in relation to human disease. Although some earlier literature is cited, this review focuses on more recent literature. The theme of this review is that multiple mechanisms are involved in acrolein toxicity. In our extensive assessment of the current literature, we aimed not only to describe these distinct mechanisms, but also to identify an overall pathway that may initiate and propagate acrolein toxicity. Our analysis suggests that this common unifying pathway may not exist or is currently undistinguishable, thus necessitating further investigation of acrolein toxicity in various disease conditions. This comprehensive review begins with a brief introduction to the production, sources, and metabolism of acrolein, followed by a detailed discussion of various mechanisms of acrolein toxicity, including protein addition, oxidative stress, mitochondrial dysfunction, DNA addition, endoplasmic reticulum ( ER) ) stress, inflammatory and immune alterations, structural and membrane effects, and dysregulated signal transduction.
In addition to endogenous production (metabolism and lipid peroxidation), humans are exposed to acrolein through oral (food and water), respiratory (cigarette smoke, vehicle exhaust, and use of fungicides) and dermal routes.
