Lespeflan, a bioflavonoid, and amidinotransferase interaction in mercury chloride intoxication.
Amidinotransferase (transamidinase, L-arginine: glycine amidinotransferase, EC 2.1.4.1) is an enzyme that catalyses the first step in creatine synthesis primarily in the kidney and pancreas. The kidney is also the primary target organ for the toxic effect of mercury. Therefore, we studied the effect of acute uremic syndrome on enzyme activity induced by mercury chloride. Because of the potential beneficial effect of bioflavonoids, we have investigated the effects of the bioflavonoid lespeflan on acute uremic syndrome and amidinotransferase activity. Male Spraque Dawley rats weighing about 200 g were used in this study. Acute renal failure was induced by intraperitoneally (i.p.) administration of mercury chloride in a dose of 3 mg/kg. One group of animals was given lespeflan (1.0 mL/kg) 1 hr before mercury chloride administration. Urea and creatinine levels in blood plasma were significantly elevated 48 hr after the induction of acute uremic syndrome (p< 0.001). Kidney transamidinase activity was decreased compared to the control group (p<0.001). Pretreatment by lespeflan potentiates the inhibitory effect of mercury chloride on enzyme activity. We discussed mechanisms of transamidinase inhibition and point thiol group of cysteine forming thiol-conjugates on enzyme inhibition both by mercury and lespeflan.
Nikolic
Jelenka
J
Department of Biochemistry, School of Medicine, University of Nis, Nis, Serbia and Montenegro. nikdan@bankerinter.net
Sokolovic
Dusan
D
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000201:enzymology*; D000579:Amidinotransferases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004347:Drug Interactions; D005419:Flavonoids / Q000494:pharmacology*; D007677:Kidney Function Tests; D008297:Male; D008627:Mercuric Chloride; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors
D005419:Flavonoids; C085745:lespeflan; D008627:Mercuric Chloride; D003404:Creatinine; D000579:Amidinotransferases; C020681:glycine amidinotransferase