(-)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors.
This study was carried out to elucidate whether the protective activity of (-)-epicatechin 3-O-gallate (ECg) against excessive peroxynitrite (ONOO(-)) production, is distinct from the activity of several well-known free radical inhibitors, the ONOO(-) inhibitors ebselen and uric acid, the superoxide anion (O(2)(-)) scavenger copper zinc superoxide dismutase (CuZnSOD) and the selective inducible nitric oxide synthase inhibitor L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL). To generate ONOO(-), male Wistar rats (n = 6/group) were subjected to ischaemia-reperfusion process together with lipopolysaccharide (LPS) injection. Although ECg did not scavenge the ONOO(-) precursors nitric oxide (NO) and O(2)(-), it reduced the 3-nitrotyrosine level, a property similar to that of uric acid, but distinct from L-NIL. In addition, the elevation in myeloperoxidase activity was reversed by the administration of ECg, uric acid and SOD, but not by that of L-NIL. Furthermore, ECg was the more potent scavenger of the ONOO(-) decomposition product, the hydroxyl radical (*OH), than any other free radical inhibitor tested. The LPS plus ischaemia-reperfusion process resulted in renal dysfunction, estimated by measuring the parameters of renal function--serum urea nitrogen and creatinine levels. However, administration of ECg ameliorated renal dysfunction more than that of the other free radical inhibitors. Moreover, ECg reduced the excessive uric acid level, while the others did not, suggesting a property of ECg distinct from the others. Furthermore, proteinuria, which was demonstrated by the low- and high-molecular weight (LMW and HMW) protein bands of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern, caused by LPS plus ischaemia-reperfusion, was attenuated by administration of ECg and L-NIL, after which the HMW band intensities decreased and LMW protein bands were absent. This study indicates that, in an in-vivo model of ONOO(-) generation, ECg, L-NIL and uric acid exert stronger protective activity against ONOO(-)-induced oxidative damage than SOD and ebselen, and that the mechanism whereby ECg protects against ONOO(-) is distinct from that of L-NIL or uric acid.
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. yokozawa@ms.toyama-mpu.ac.jp
Takako
T
Yokozawa
Dong Young
DY
Rhyu
Eun Ju
EJ
Cho
D000818:Animals; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000627:therapeutic use*; D003300:Copper / Q000737:chemistry; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000037:antagonists & inhibitors; D054833:Isoindoles; D007564:Japan; D007668:Kidney / Q000098:blood supply / Q000201:enzymology / Q000293:injuries; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications; D012250:Rheum / Q000737:chemistry; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D014443:Tyrosine / Q000819:agonists / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D014527:Uric Acid / Q000097:blood; D015032:Zinc / Q000737:chemistry
D001393:Azoles; D016166:Free Radical Scavengers; D054833:Isoindoles; D008070:Lipopolysaccharides; C090663:N(6)-(1-iminoethyl)lysine; D016566:Organoselenium Compounds; D010936:Plant Extracts; D014527:Uric Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; C042986:ebselen; D014443:Tyrosine; D003300:Copper; D002392:Catechin; C062669:epicatechin gallate; D003404:Creatinine; D009195:Peroxidase; D013482:Superoxide Dismutase; D015032:Zinc; D008239:Lysine