Antioxidant and pro-oxidant assay for a new drug GEPC: detected by ESR spectrometry and by protective effects on lipid peroxidation and biomolecule degradation.
L-Ascorbic acid 2-(20 beta-11-oxo-olean-12-en-29-oic acid ethylester-3-beta-yl hydrogen phosphate) sodium salt (GEPC) is a newly synthesized compound representing a phosphate diester linkage of glycyrrhetic acid ethylester and ascorbic acid. In the present study, we found that GEPC effectively inhibited Fe(III)-ADP/NADPH-induced peroxidation of liver microsomes. The inhibitory effect was much greater than that of glycyrrhetic acid (GA), and contrasted with the stimulatory effect of ascorbic acid. An ESR study showed that GEPC appeared to have a great loss of the DPPH and superoxide radical scavenging effects of ascorbic acid. However, GEPC, like ascorbic acid, inhibited hydroxyl radicals generation in both Fe(II)-H2 O2 and Cr(VI)-H2 O2 systems. GEPC, unlike ascorbic acid, showed no pro-oxidant effect and acted as an effective iron-chelating agent in the ESR study or in the iron-induced deoxyribose and DNA degradation assays. The hydroxyl radical scavenging effect of GEPC was further demonstrated by its protective effect on the hydroxyl radical- induced degradation of certain biomolecules, i.e., carbohydrates, amino acids, and DNA. These results demonstrate that beside its protective effect on ascorbic acid autoxidation and increasing water solubility of GA, GEPC is also an antioxidant though not so powerful as ascorbic acid but more powerful than GA.
Liu
J
J
Department of Neuroscience, Okayama University Medical School, Japan.
Mori
A
A
Ogata
K
K
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D050260:Carbohydrate Metabolism; D004247:DNA / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006900:Hydroxylation / Q000187:drug effects; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D000975:Antioxidants; D001565:Benzoates; D016166:Free Radical Scavengers; D016877:Oxidants; C085728:ascorbic acid 2-(11-oxoolean-12-en-29-oic acid ethyl ester 3-yl-phosphate); D019817:Benzoic Acid; D004247:DNA; D006034:Glycyrrhetinic Acid; D001205:Ascorbic Acid