Generation of Superoxide Anions during the Reaction of Guanidino Compounds with Methylglyoxal.

Abstract

Uremic toxins are accumulated in the blood of patients with chronic renal failure (CRF), although alteration of the toxicity by the interaction of various uremic retention products has not been precisely clarified. In this study, we found that cytochrome c added to incubation mixtures containing guanidino compounds and methylglyoxal in phosphate buffer solution (pH 7.4) resulted in reduction of cytochrome c. Superoxide anions were generated from incubation mixtures of each guanidino compound with methylglyoxal, because the reduction was inhibited by the addition of superoxide dismutase. The incubation mixture containing each guanidino compound and methylglyoxal had different rates of generation of the superoxide anion from other mixtures. A relatively higher superoxide anion formation rate was observed in the incubation mixture containing Arg and methylglyoxal (7.9؎0.5 nmol · m ؊1 · min ؊1 ), or in the incubation mixture containing methylguanidine and methylglyoxal (6.3؎0.6 nmol · ml ؊1 · min ؊1). These findings suggest that interactions of various uremic retention products which accumulate in the blood of uremic patients may generate reactive oxygen species and may be involved in the oxidative stress observed in CRF patients. The addition of aminoguanidine, which is known to inhibit the formation of advanced glycation end products, to a mixture of guanidino compounds and methylglyoxal inhibited reactions between guanidino compounds and methylglyoxal.

Shortage of Lipid-radical Cycles in Membranes as a Possible Prime Cause of Energetic Failure in Aging and Alzheimer Disease

“…Among the aldehydes are products of lipid peroxidation as well as products of anomalous glucose metabolism (glyoxal and methylglyoxal, MG) [62,73,74]. Pioneering works of Szent-Gyorgi [75] inspired the interest to MG, an intermediate product of carbohydrate metabolism.…”

Ferricytochrome c Directly Oxidizes Aminoacetone to Methylglyoxal, a Catabolite Accumulated in Carbonyl Stress

“…It has also been found to depress reduced glutathione in cultures of rat hepatocytes [62], possibly via inhibition of glutathione reductase [63] and glutathione peroxidase [64], and to induce cellular swelling and apoptosis of pancreatic β-cells [65], [66]. Furthermore, MG reportedly produces free radicals during the glycation of amino acids, including alanine [67], and superoxide radicals from its reaction with guanidine compounds [68].…”

Gas Chromatographic Analysis of Guanidino Compounds in Sera and Urine of Uremic Patients Using Glyoxal and Ethyl Chloroformate as Derivatizing Reagents

“…27 They are reported to react with guanidino compounds in proteins and modify arginine residues. [28][29][30][31][32][33] The reactions are reported to occur at physiological concentrations. GC elution of the guanidino compounds: G, MG, GAA, guanidinopropionic acid (GPA), ganidinobutyric acid (GBA) and GSA is possible after derivatization with glyoxal.…”