Acetaldehyde formation and accumulation. Toxic effects on reproductive target tissues during alcohol drinking

J.A. CASTRO; G.D. CASTRO

Acetaldehyde: Biochemistry, Applications and Safety Concerns

Nova Science Publishers Inc.

Lugar: Hauppauge; Año: 2015; p. 79 - 129

Health consequences derived from alcohol drinking are a problem of increasing relevance worldwide. Ethanol toxicity is due essentially to its biotransformation products, acetaldehyde and different types of free radicals, which cause oxidative stress. Given that acetaldehyde and free radicals are highly reactive species is important to consider that, if generated in situ in a target tissue, they may cause toxicity. Oxidation of ethanol to acetaldehyde (and free radicals) is likely to proceed through a variety of enzymatic pathways and proved to occur in different tissues, including those from the reproductive system of both sexes. In this case, metabolic pathways involved do not include necessarily the same enzymes oxidizing ethanol in the liver. We demonstrated the existence of several pathways able to generate both, acetaldehyde and free radicals, in those tissues. The relation between the ability to generate toxic metabolites and the one to destroy them is very important but highly variable and depending on the body site. In all the tissues studied, alcohol exposure provoked an oxidative stress process, linked to the fact that pro-oxidant species were generated. These tissues do not have efficient mechanisms for detoxification of acetaldehyde generated in situ or arriving to them via blood. This may lead to a long lasting accumulation of this metabolite which, by decreasing the glutathione content, would reduce the tissue capacity to detoxify both, acetaldehyde and reactive oxygen species. Ethanol is a chemical with the ability to modify the metabolism of other toxins and the content of endogenous substances like hormones. Organs like the ones constituting reproductive system in both sexes can be affected by exposure to alcohol in an indirect way, when exposure to other toxic substances in the environment takes place, and when levels of hormones critical to the development and function of these organs can change. In summary, alcohol toxicity in reproductive systems of both sexes is subjected to multifactorial mechanisms that include genetic, hormonal, dietary and environmental components. In situ metabolism, however, should be regarded as an important contributing factor because of a principle of similitude, that is, the same toxic metabolites can initiate the early steps of cellular alterations in any tissue, no matter where and how are generated. In this review we analyze data generated by our laboratory and from others on the deleterious effects of ethanol oxidation to acetaldehyde and free radicals in tissues from the reproductive system of both sexes.