title: Antioxidant action of 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid, an efficient aldose reductase inhibitor, in a 1,1'-diphenyl-2-picrylhydrazyl assay and in the cellular system of isolated erythrocytes exposed to tert-butyl hydroperoxide.
abstract: OBJECTIVE
  The subject of this study was 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (compound 1), an efficient aldose reductase inhibitor of high selectivity. The antioxidant action of 1 was investigated in greater detail by employing a 1,1'-diphenyl-2-picrylhydrazyl (DPPH) test and in the system of isolated rat erythrocytes.
  
  
  METHODS
  First, the compound was subjected to the DPPH test. Second, the overall antioxidant action of the compound was studied in the cellular system of isolated rat erythrocytes oxidatively stressed by free radicals derived from the lipophilic tert-butyl hydroperoxide. The uptake kinetics of 1 was studied and osmotic fragility of the erythrocytes was evaluated.
  
  
  RESULTS
  The DPPH test revealed significant antiradical activity of 1. One molecule of 1 was found to quench 1.48 ± 0.06 DPPH radicals. In the system of isolated erythrocytes, the compound was readily taken up by the cells followed by their protection against free radical-initiated hemolysis. Osmotic fragility of the erythrocytes was not affected by 1.
  
  
  CONCLUSIONS
  The results demonstrated the ability of 1 to scavenge DPPH and to protect intact erythrocytes against oxidative damage induced by peroxyl radicals. By affecting both the polyol pathway and oxidative stress, the compound represents an example of a promising agent for multi-target pharmacology of diabetic complications.
authors.forename: Marta Soltesova
authors.initials: MS
authors.lastname: Prnova
authors.forename: Jana
authors.initials: J
authors.lastname: Ballekova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Majekova
authors.forename: Milan
authors.initials: M
authors.lastname: Stefek
mesh_terms: D019342:Acetic Acid / Q000737:chemistry*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects*; D005609:Free Radicals / Q000737:chemistry; D006461:Hemolysis; D007210:Indoleacetic Acids / Q000737:chemistry; D008297:Male; D009995:Osmosis; D018384:Oxidative Stress; D010851:Picrates / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000737:chemistry; D020122:tert-Butylhydroperoxide / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D005609:Free Radicals; D007210:Indoleacetic Acids; D010851:Picrates; D013438:Sulfhydryl Compounds; C000611863:cemtirestat; D020122:tert-Butylhydroperoxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D000449:Aldehyde Reductase; D019342:Acetic Acid
keywords: 2; 3-Mercapto-5H-1; 4-triazino[5; 6-b]indole-5-acetic acid; Aldose reductase inhibitor; Antioxidant; DPPH assay; Hemolysis; t-BuOOH