• Specificity of free radical quenching
• Metal chelating activity
• Interaction with other antioxidants
• Effects on gene expression
Other criteria are important when considering preventive
or therapeutic applications:
• Absorption and bioavailability
• Concentration in tissues, cells, and extracellular
fluid
• Location (in aqueous or membrane domains or in
both?)
A substance need not excel in meeting all these
criteria to be considered a good antioxidant. For example,
vitamin E acts only in the membrane or lipid domains,
its dominant action is to quench lipid peroxyl
radicals, and it has little or no activity against radicals
in the aqueous phase, yet it is considered one of the
central antioxidants of the body. Epidemiological studies
are confirming its role in the prevention of numerous
oxidant-related diseases, such as heart disease. 7"s
An "ideal" antioxidant would fulfill all of the
above criteria. The c~-lipoic acid/dihydrolipoic acid redox
couple approaches the ideal; it has been called
"a universal antioxidant. ''9 a-Lipoic acid is readily
absorbed from the diet. It is probably rapidly converted
to DHLA in many tissues, as recent advances in assay
technique have made evident) °'H One or both of the
components of the redox couple effectively quench a
number of free radicals in both lipid and aqueous domains.
Both DHLA 21'32'33 and a-lipoic acid 13'19"23'24
have metal-chelating activity. DHLA acts synergistically
with other antioxidants, indicating that it is capable
of regenerating other antioxidants from their radical
or inactive forms. Finally, there is evidence that they
may have effects on regulatory proteins and on genes
involved in normal growth and metabolism.
Because of these antioxidant attributes, a number
of experimental and clinical studies have been carried
• Specificity of free radical quenching• Metal chelating activity• Interaction with other antioxidants• Effects on gene expressionOther criteria are important when considering preventiveor therapeutic applications:• Absorption and bioavailability• Concentration in tissues, cells, and extracellularfluid• Location (in aqueous or membrane domains or inboth?)A substance need not excel in meeting all thesecriteria to be considered a good antioxidant. For example,vitamin E acts only in the membrane or lipid domains,its dominant action is to quench lipid peroxylradicals, and it has little or no activity against radicalsin the aqueous phase, yet it is considered one of thecentral antioxidants of the body. Epidemiological studiesare confirming its role in the prevention of numerousoxidant-related diseases, such as heart disease. 7"sAn "ideal" antioxidant would fulfill all of theabove criteria. The c~-lipoic acid/dihydrolipoic acid redoxcouple approaches the ideal; it has been called"a universal antioxidant. ''9 a-Lipoic acid is readilyabsorbed from the diet. It is probably rapidly convertedto DHLA in many tissues, as recent advances in assaytechnique have made evident) °'H One or both of thecomponents of the redox couple effectively quench anumber of free radicals in both lipid and aqueous domains.Both DHLA 21'32'33 and a-lipoic acid 13'19"23'24have metal-chelating activity. DHLA acts synergisticallywith other antioxidants, indicating that it is capableof regenerating other antioxidants from their radicalor inactive forms. Finally, there is evidence that theymay have effects on regulatory proteins and on genesinvolved in normal growth and metabolism.Because of these antioxidant attributes, a numberof experimental and clinical studies have been carried
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