Abstract Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure.
In addition, acetaldehyde contributes to the accumulation of another TIQ, tetrahydropapaveroline, which is produced by the reaction of dopamine with dopaldehyde, an intermediate in dopamine metabolism. Acetaldehyde inhibits the normal breakdown of dopaldehyde, leading to its accumulation and increased formation of tetrahydropapaveroline.
Both salsolinol and tetrahydropapaveroline exhibit reinforcing properties and induce a long- lasting increase in voluntary alcohol consumption in rodents and monkeys Quertemont et al.
Both compounds therefore are believed to contribute to the development of alcoholism; however, their neurochemical mechanisms of action remain unknown. Similarly, it is unclear whether the concentrations of these TIQ and THBC alkaloids that are achieved in the brain after alcohol consumption are pharmacologically relevant.
The answers to these questions are critical for determining whether these acetaldehyde adducts do indeed play a role in the neuropharmacological effects of alcohol. In summary, acetaldehyde is a pharmacologically active compound that acts either directly or through the formation of adducts to induce effects in both the periphery and the brain.
Of particular interest, some of the behavioral effects of acetaldehyde are similar to those of ethanol, leading to the suggestion that acetaldehyde may be involved in mediating these effects of alcohol.
For example, a growing body of evidence indicates that acetaldehyde shows reinforcing properties. Therefore, it has been speculated that acetaldehyde contributes to the motivation to drink alcohol and, consequently, to the development of alcoholism Brown et al. Although this question has long been debated, controversy still exists.
After alcohol ingestion, acetaldehyde mainly is produced during ethanol breakdown in the liver, which primarily Alcohol and acetaldehyde the enzyme ADH but also cytochrome PE1 and the enzyme catalase. Because of the high efficiency of the liver ALDH, however, acetaldehyde is rapidly converted to acetate and little acetaldehyde reaches the blood circulation.
Therefore, under normal physiological conditions, acetaldehyde concentrations in the blood following alcohol administration usually are very low or even undetectable. Because acetaldehyde must act on the brain to induce behavioral effects, the physiological acetaldehyde concentrations in the brain and other organs also have been investigated.
ADH, the main ethanol-metabolizing enzyme, is not physiologically active in the brain, and researchers long have assumed that the CNS cannot metabolize alcohol and produce acetaldehyde.
However, recent findings suggest that the brain can produce acetaldehyde from local ethanol metabolism involving mainly catalase and cytochrome PE1 Zimatkin et al. Moreover, studies conducted with cultured cells i.
This failure also may be due to the fact that acetaldehyde concentrations after ethanol administration differ among brain regions because the acetaldehyde-producing enzymes are not evenly distributed across various brain cells Zimatkin and Lindros It is therefore possible that past attempts to measure brain acetaldehyde concentrations underestimated its potential neurochemical actions.
Moreover, it is possible that although low acetaldehyde concentrations themselves have no measurable effects, they may suffice to synergistically enhance the effects of ethanol. In summary, it remains unclear whether the acetaldehyde concentrations achieved in different organs, especially in the brain, after alcohol consumption under normal physiological conditions are biologically relevant.
Finding the answer to this question will be critical for definitively determining whether acetaldehyde contributes to the effects of ethanol in vivo.
Another strategy to determining whether acetaldehyde mediates or modulates the effects of ethanol is to modify physiological acetaldehyde concentrations by interfering with normal ethanol metabolism.
This approach is described in the next section. To this end, several animal studies have used pharmacological agents that alter normal ethanol metabolism. In the periphery, the high efficiency of liver ALDH prevents acetaldehyde produced in the liver from escaping into the blood circulation; as a result, changes in ADH activity do not significantly alter blood acetaldehyde concentrations if ALDH is not inhibited at the same time.
To circumvent these problems, changes in peripheral or CNS acetaldehyde concentrations are typically achieved by modulating the activity of ALDH and of the acetaldehyde-producing enzyme catalase see Figure 1. Several ALDH inhibitors have been used to cause massive acetaldehyde accumulation after alcohol consumption, most commonly disulfiram and cyanamide.
When ALDH is pharmacologically inhibited, acetaldehyde accumulates to high concentrations both in the brain and in the periphery. Catalase metabolizes about 60 percent of ethanol in the brain. Therefore, inhibition of catalase is believed to reduce brain acetaldehyde levels, whereas enhancement of catalase activity is believed to increase brain acetaldehyde levels.
Effects of ALDH Inhibition Ethanol administration to animals or humans following treatment with ALDH inhibitors leads to the typical alcohol sensitivity reaction, which then deters further alcohol consumption.
Accordingly, most animal studies using ALDH inhibitors have focused on measuring subsequent alcohol consumption in order to establish a model for predicting the efficacy of ALDH inhibitors as alcohol-deterrent medications in alcoholism treatment.
These studies generally concluded that ALDH inhibition and acetaldehyde accumulation strongly reduce voluntary alcohol consumption and potentiate the aversion for moderate to high ethanol doses Quertemont et al. As a result of the manipulation, these mice lack active ALDH in the liver and therefore eliminate acetaldehyde at a very low rate.
They also displayed the typical symptoms of the alcohol sensitivity reaction, such as redness of the skin i.Acetaldehyde (systematic name ethanal) is an organic chemical compound with the formula CH 3 CHO, sometimes abbreviated by chemists as MeCHO In the brain, the enzyme catalase is primarily responsible for oxidizing ethanol to acetaldehyde, and alcohol dehydrogenase plays a minor role.
When any drinker consumes alcohol, it is acetaldehyde that is responsible for a hangover and is the cause of alcohol associated disease. Cigarette Smoke Acetaldehyde is present in tobacco smoke, and is the most abundant carcinogen found in tobacco, contributing to mouth, lung, and throat cancers.
Mar 25, · Alcohol abuse is a serious medical and social problem. Although light to moderate alcohol consumption is beneficial to cardiovascular health, heavy drinking often results in organ damage and social problems. When any drinker consumes alcohol, it is acetaldehyde that is responsible for a hangover and is the cause of alcohol associated disease.
Cigarette Smoke Acetaldehyde is present in tobacco smoke, and is the most abundant carcinogen found in tobacco, contributing to mouth, lung, and throat cancers.
New evidence shows that drinking alcohol is the greatest risk factor for acetaldehyde-related cancer.
Heavy drinkers may be at increased risk due to exposure from multiple sources. The research. Acetaldehyde is a colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors.
It is also an intermediate in the metabolism of alcohol.