Antioxidant activity of a Schiff base of pyridoxal and aminoguanidine.
We recently reported that PL-AG, a Schiff base of pyridoxal and aminoguanidine, was more effective than aminoguanidine (AG), a well-known anti-diabetic-complication compound, in preventing nephropathy in diabetic mice and presented brief data indicating the antioxidant activity of the adduct. In the present study, we additionally investigated the inhibitory activity of PL-AG in comparison with that of AG against in vitro and in vivo oxidation. PL-AG was more potent than AG and reference compounds such as pyridoxal and pyridoxamine in any of the five antioxidant activities examined in vitro, i.e., hydrogen peroxide-scavenging, hydroxyl radical-scavenging, superoxide radical-scavenging, ascorbic acid-autoxidation inhibitory, and low-density lipoprotein (LDL)-oxidation inhibitory activities, the last two of which were assessed in the presence of Cu(2+). Unlike AG, PL-AG did not show the pro-oxidant activity. The inhibitory activity of PL-AG against lipid peroxidation in diabetic rats was higher than that of AG, for example, the amounts of malondialdehyde in erythrocytes (nmol/g hemoglobin; mean +/- SD) in normal, untreated diabetic, AG-treated diabetic, and PL-AG-treated diabetic rats were 3.53 +/- 0.35, 4.99 +/- 0.23, 4.65 +/- 0.45, and 4.06 +/- 0.35, respectively. A fluorescent substance different from PL-AG was found in the plasma and urine of rats treated with PL-AG. The chemical structure of this substance, i.e., oxidized PL-AG, was determined by a combination of nuclear magnetic resonance, mass, and infrared spectrometry. AG dramatically decreased the pyridoxal phosphate level in the diabetic rat liver, whereas PL-AG only moderately affected it. Our results indicate that the antioxidant activity of PL-AG is due to its chelation with transition metal ions and to scavenging of reactive oxygen species. They also suggest that PL-AG is more promising for the treatment of diabetic complications than AG.
Chen
An-Shu
AS
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Taguchi
Tadao
T
Aoyama
Sayaka
S
Sugiura
Michiharu
M
Haruna
Mitsumasa
M
Wang
Min-Wei
MW
Miwa
Ichitomo
I
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy; D003921:Diabetes Mellitus, Experimental; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D006146:Guanidines / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007477:Ions; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008315:Malondialdehyde / Q000494:pharmacology; D013058:Mass Spectrometry; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D016877:Oxidants / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011730:Pyridoxal / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013053:Spectrophotometry; D013055:Spectrophotometry, Infrared; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D001565:Benzoates; D001786:Blood Glucose; D005456:Fluorescent Dyes; D006146:Guanidines; D007477:Ions; D008077:Lipoproteins, LDL; D016877:Oxidants; D017382:Reactive Oxygen Species; D013481:Superoxides; D011730:Pyridoxal; D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D001219:Aspartate Aminotransferases; D001205:Ascorbic Acid; D010100:Oxygen; C004479:pimagedine