Influence of pyridoxylidene aminoguanidine on biomarkers of the oxidative stress and selected metabolic parameters of rats with diabetes mellitus

Gen Physiol Biophys. 2009 Dec;28(4):347-55.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Animals
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • DNA Damage
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / chemically induced
  • Diabetes Mellitus / enzymology
  • Diabetes Mellitus / metabolism*
  • Guanidines / administration & dosage
  • Guanidines / chemistry
  • Guanidines / pharmacology*
  • Lipoproteins / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Pyridoxal / administration & dosage
  • Pyridoxal / chemistry
  • Pyridoxal / pharmacology*
  • Rats
  • Rats, Wistar
  • Solubility
  • Water / chemistry

Substances

  • Aldehydes
  • Antioxidants
  • Biomarkers
  • Guanidines
  • Lipoproteins
  • pyridoxylidene aminoguanidine
  • Water
  • Pyridoxal
  • Malondialdehyde
  • 4-hydroxy-2-nonenal
  • pimagedine