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.