Acrolein‐mediated injury in nervous system trauma and diseases

Abstract

Acrolein, an α,β-unsaturated aldehyde, is a ubiquitous pollutant that is also produced endogenously through lipid peroxidation. This compound is hundreds of times more reactive than other aldehydes such as 4-hydroxynonenal, is produced at much higher concentrations, and persists in solution for much longer than better known free radicals. It has been implicated in disease states known to involve chronic oxidative stress, particularly spinal cord injury and multiple sclerosis. Acrolein may overwhelm the anti-oxidative systems of any cell by depleting glutathione reserves, preventing glutathione regeneration, and inactivating protective enzymes. On the cellular level, acrolein exposure can cause membrane damage, mitochondrial dysfunction, and myelin disruption. Such pathologies can be exacerbated by increased concentrations or duration of exposure, and can occur in normal tissue incubated with injured spinal cord, showing that acrolein can act as a diffusive agent, spreading secondary injury. Several chemical species are capable of binding and inactivating acrolein. Hydralazine in particular can reduce acrolein concentrations and inhibit acrolein-mediated pathologies in vivo. Acrolein scavenging appears to be a novel effective treatment which is primed for rapid translation to the clinic.

Determination of Urine 3-HPMA, a Stable Acrolein Metabolite in a Rat Model of Spinal Cord Injury

“…This finding may prove more useful as lower levels of acrolein (*1-25 lM) are more likely to be pathologically relevant in the clinic. 1,5,21 One interesting phenomena is that overall the number of 3-HPMA molecules produced was greater than the amount of acrolein injected to the spinal cord (Fig. 4B, C).…”

“…This phenomenon is consistent with the understanding that acrolein is both the product and the catalyst of oxidative stress. 1,3,17 Acrolein has the ability to further stimulate the production of free radicals, and consequently lipid peroxidation-a process that leads to even more acrolein production. 5,[21][22][23] Therefore, acrolein is known to be self-regenerative that could FIG.…”

“…1,2 This is based on its high direct toxicity to various cells by attacking DNA, proteins, lipids, and mitochondria, [3][4][5][6] perpetuating oxidative stress by further stimulating the production of free radicals, 1,5 and having an extended presence within biological systems to exert its prolonged toxicity. 7,8 In light of the pathological importance of acrolein, the detection and quantification of acrolein is of significant importance in delineating the pathogenesis of various diseases.…”

Effects of Switching to Electronic Cigarettes with and without Concurrent Smoking on Exposure to Nicotine, Carbon Monoxide, and Acrolein

“…Its adverse effects are dose-and cell type-dependent and influenced by experimental conditions (7). Animal experiments showed that acrolein can have a range of adverse effects, including a role in carcinogenesis (8,9); excessive mucus production and macrophage and neutrophil accumulation with consequent production of proinflammatory cytokines and proteases (10); damage to neurons and myelin disruption (11); and may play a role in the progression of atherosclerosis (12) and cardiovascular disease (13). The main pathway for elimination of acrolein is conjugation with glutathione (GSH) in the liver, followed by enzymatic cleavage of the g-glutamic acid and glycine residues, respectively, in the liver and in the kidney and N-acetylation of the resultant cysteine conjugate to form S-(3-oxopropyl)-Nacetylcysteine (OPMA) in the kidney.…”

The Role of TRP Channels in Migraine

“…Oxidative stress, caused by tissue damage or other pathological processes can result in accumulations of acrolein and 4-hydroxynonenal due to lipid peroxidation. Acrolein is highly reactive, has a long half-life and can diffuse some distance from the site of injury in animal models of mild traumatic brain injury [203]. As both acrolein and 4-hydroxynonenal are TRPA1 activators it is conceivable that their accumulation under these conditions may contribute to migraine susceptibility in multiple sclerosis and brain injury.…”