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Lipoic Acid: A Molecule with an Intriguing Past and a Promising Future

Por: | 23 de septiembre de 2013

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By Anna Bilska, Jagiellonian University in Krakow

Lipoic acid, a compound discovered in the 1950s, is a molecule consisting of eight carbon atoms, two oxygen atoms and two sulfur atoms. During the decade that followed its discovery, researchers focused mostly on its structure and its role in metabolism; only a few of about 300 papers published at that time dealt with its therapeutic potential. The past two decades, however, have witnessed a surge of interest in the pharmacology of lipoic acid, particularly its therapeutic effects in the treatment of many apparently unrelated diseases, of which diabetes, atherosclerosis, neurodegenerative changes, joint diseases and AIDS are the ones studied most often. And the interest is already paying off.

  • High doses of lipoic acid are currently recommended in many countries for the treatment of diabetic neuropathies, a family of nerve disorders caused by diabetes. 
  • Available data indicate a positive effect of lipoic acid preparations (creams, ointments, etc.) on the skin, and such creams are already available off the shelf.
  • Sportspersons are being prescribed lipoic acid preparations for relief from oxidative stress caused by exercise and for faster growth of muscles.

Our attention was drawn to the studies linking lipoic acid with the activity of two enzymes, namely aldehyde dehydrogenase and rhodanese.

Aldehyde dehydrogenase decreases the concentration of aldehydes in all tissues by oxidizing the aldehydes to acids. Aldehydes are a product of normal metabolism and also of the metabolism of xenobiotics, which are compounds foreign to an organism (drugs, poisons, food preservatives, alcohol, etc.). Aldehydes are toxic, mutagenic and carcinogenic. The greater the activity of aldehyde dehydrogenase, the lower the concentration of aldehydes, which is why compounds that boost the activity of aldehyde dehydrogenase can be useful in clinical practice.

Recent studies suggest that aldehyde dehydrogenase can be a part of new treatments for cardiovascular diseases and cancer, and researchers have been interested in finding out ways to inhibit the enzyme as well as to activate it. Activation of aldehyde dehydrogenase has proved beneficial to the cardiovascular system following bouts of ischemia whereas specific inhibition of the enzyme has proved useful in developing aversion to alcohol and, more recently, in treating cocaine addiction. Most studies have shown aldehydes to be antimitotic and therefore inhibitory to carcinogenesis — a property likely to be beneficial because inhibiting aldehyde dehydrogenase will increase aldehyde levels in tissues and thus arrest uncontrolled proliferation of cells. Secondly, aldehyde dehydrogenase is commonly over-expressed in cancer; if the enzyme is inhibited, the cells in which it has been inhibited are likely to show high levels of aldehydes, which can therefore serve as a marker of cancerous stem cells.

Our pilot study indicated that lipoic acid decreases the activity of aldehyde dehydrogenase in rat livers.

Rhodanese, the second enzyme linked lipoic acid, neutralizes cyanide. This is a particularly important role because several cyanide compounds are produced during industrial processes, resulting in serious environmental pollution. Lipoic acid has been shown to be a potential agent in treating seizures and mortality induced by cyanide in mice. Rhodanese also plays several other important roles. For example, it is believed to modify protein structure by attaching sulfur to the protein macromolecules, thereby influencing their activity. We believe that lipoic acid can influence the activity of rhodanese, and our studies provide adequate evidence to support this belief: when we probed the link between lipoic acid and rhodanese activity, we found clear evidence that, in rats, lipoic acid increases rhodanese activity in the heart, liver and kidneys.

To conclude, our studies can shed a new light on the role of aldehyde dehydrogenase and rhodanese in the development of many diseases and on their treatment and, since lipoic acid modulates the activity of both these enzymes, our work offers fresh opportunities to exploit its pharmacological potential.


Anna Bilska
Jagiellonian University in Krakow

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