Pyridoxal-aminoguanidine adduct is more effective than aminoguanidine in preventing neuropathy and cataract in diabetic rats.
We examined the ability of a pyridoxal-aminoguanidine adduct with both antiglycation and antioxidant activities in vitro to protect against neuropathy and cataract in streptozotocin-diabetic rats and compared the result with that of aminoguanidine. In vivo antiglycation and antioxidant activities were also compared between the adduct and aminoguanidine. Diabetic rats were given either of the compounds in their drinking water (9 mM) for 7 weeks. Neither compound affected body weight, blood glucose level or urine volume. The adduct, but not aminoguanidine, significantly improved motor nerve conduction velocity. The time to develop cataract was longer in adduct-treated rats than in untreated and aminoguanidine-treated rats. The increase in opacification of lenses in culture medium containing high glucose levels (55.5 mM) was more efficiently attenuated by the adduct than by aminoguanidine. Adduct and aminoguanidine similarly lowered glycated hemoglobin levels. The level of urinary 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage, and the level of liver malondialdehyde plus 4-hydroxy-2-alkenals, a marker of tissue lipid peroxidation, both of which were elevated by diabetes, were significantly reduced by the adduct but not by aminoguanidine. These findings indicate that the pyridoxal-aminoguanidine adduct is superior to aminoguanidine in preventing diabetic neuropathy and cataracts, and we suggest that this may be at least partly due to the higher antioxidant activity of the former.
Chen
A-S
AS
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Taguchi
T
T
Sugiura
M
M
Wakasugi
Y
Y
Kamei
A
A
Wang
M-W
MW
Miwa
I
I
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000503:physiopathology / Q000652:urine; D003929:Diabetic Neuropathies / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005947:Glucose; D006442:Glycated Hemoglobin; D006146:Guanidines; D011730:Pyridoxal; C471830:aminoguanidine pyridoxal adduct; C004479:pimagedine