Influence of pyridoxylidene aminoguanidine on biomarkers of the oxidative stress and selected metabolic parameters of rats with diabetes mellitus.
Oxidative damage is considered to play an important role in the pathogenesis of several diseases, such as diabetes mellitus (DM), atherosclerosis, cardiovascular complications and chronic renal failure. DM is associated with the oxidative stress and formation of advanced glycation end products (AGEs). Different drugs inhibit oxidative stress and formation of advanced glycation end products. Aminoguanidine (AG) has been proposed as a drug of potential benefit in prophylaxis of the complications of DM. Recent reports show a pro-oxidant activity of AG. Therefore we examined the effect of structural analogue of AG, its Schiff base with pyridoxal-pyridoxylidene aminoguanidine (PAG) on the level of selected markers of oxidative stress. We found that PAG decreased total damage to DNA in controls as well as in diabetic group of rats. However, we also found that PAG supplementation increases susceptibility of lipoproteins to oxidation and formation of conjugated dienes in both, diabetic as well as control animals. Its administration to diabetic rats decreases antioxidant capacity of plasma. Therefore, it is necessary to search for other structural modifications of AG that would combine its higher anti-diabetic activity with less toxicity.
Országhová
Zuzana
Z
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, and Department of Biochemistry and Hematology, State Hospital, Sasinkova 2, 813 72 Bratislava, Slovakia.
Liptáková
Anna
A
Muchová
Jana
J
Ulicná
Ol'ga
O
Vancová
Ol'ga
O
Sivonová
Monika
M
Bozek
Peter
P
Cársky
Jozef
J
Duracková
Zdenka
Z
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D004249:DNA Damage; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D006146:Guanidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011730:Pyridoxal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014867:Water / Q000737:chemistry
D000447:Aldehydes; D000975:Antioxidants; D015415:Biomarkers; D006146:Guanidines; D008074:Lipoproteins; C549858:pyridoxylidene aminoguanidine; D014867:Water; D011730:Pyridoxal; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal; C004479:pimagedine