In vitro and in vivo assessment of the antioxidant activity of melatonin and related indole derivatives.
Effects of melatonin and some structurally related indole compounds were studied by in vitro methods such as (i) an inhibition of the hyaluronic acid degradation and (ii) a standard lipid peroxidation assay. In vivo approach was based on the alloxan model of hyperglycaemia. Reduction of the viscosity of a hyaluronic acid solution in the reaction mixture was inhibited by tryptamine (91% inhibition), as well as by indole-3-carboxylic acid and indomethacin (80% and 77% inhibition, respectively). Lipid peroxidation with tert-butyl hydroperoxide as a source of radicals was followed by the formation of thiobarbituric acid reactive substances. Tested drugs inhibited lipid peroxidation in the order: tryptamine (59%) > indole-2-carboxylic acid (38%) > indomethacin (26%) > melatonin and indole-3-carboxylic acid (13%). In vivo, alloxan-induced hyperglycaemia was reduced in mice pretreated with drugs tested. The highest protective effect was observed with indomethacin (52% inhibition), followed by tryptamine and melatonin (18% and 16% inhibition, respectively).
Stetinová
V
V
Institute of Experimental Biopharmaceutics, Joint Research Center of the Academy of Sciences of the Czech Republic and PRO.MED.CS Praha, Hradec Králové. stetinova@uebf.cas.cz
Smetanová
L
L
Grossmann
V
V
Anzenbacher
P
P
D000496:Alloxan; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002264:Carboxylic Acids; D005260:Female; D006820:Hyaluronic Acid / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy*; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007213:Indomethacin / Q000737:chemistry / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008550:Melatonin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000737:chemistry / Q000378:metabolism
D000975:Antioxidants; D002264:Carboxylic Acids; D007211:Indoles; D014363:Tryptamines; C058980:indole-2-carboxylic acid; C030820:tryptamine; D008315:Malondialdehyde; C012382:indole-3-carboxylic acid; D000496:Alloxan; D006820:Hyaluronic Acid; D008550:Melatonin; D010100:Oxygen; D007213:Indomethacin