title: Antioxidant and antiradical properties of esculin, and its effect in a model of epirubicin-induced bone marrow toxicity.
abstract: OBJECTIVE
  To evaluate the effect of esculin, a plant coumarin glucoside, on free radicals and against epirubicin-induced toxicity on bone marrow cells.
  
  
  METHODS
  Antioxidant activity was assessed by a luminol-dependent chemiluminescence method or NBT test in a xanthine-xanthine oxidase system, and two iron-dependent lipid peroxidation systems. In vivo experiments were carried out in epirubicin-treated mice, alone or in a combination with esculin. Genotoxicity of the anthracycline drug was assessed by cytogenetic analysis and an autoradiographic assay.
  
  
  RESULTS
  Esculin inactivated superoxide anion radicals in both systems we used. It exerted SOD-mimetic effect and reduced the level of superoxide radicals generated in a xanthine-xanthine oxidase system by 30%. Esculin also showed an antioxidant effect in a model of Fe2+-induced lipid peroxidation. Cytogenetic analysis showed that epirubicin had a marked influence on the structure of metaphase chromosomes of normal bone marrow cells. Inclusion of esculin in the treatment protocol failed to ameliorate the epirubicin-induced antiproliferative effects and genotoxicity in bone marrow cells.
  
  
  CONCLUSIONS
  In this study the ability of the coumarin glucoside esculin to scavenge superoxide radicals and to decrease Fe-induced lipid peroxidation was documented. However, despite the registered antioxidant effects the tested compound failed to exert cytoprotection in models of anthracycline-induced genotoxicity in bone marrow cells. The results of this study warrant for more precise further evaluation of esculin, employing different test systems and end-points and a wider range of doses to more precisely appraise its potential role as a chemoprotective/resque agent.
authors.affiliation: Department of Pharmacology and Drug Toxicology, Medical University, Plovdiv, Bulgaria.
authors.forename: Sefedin
authors.initials: S
authors.lastname: Biljali
authors.forename: Vera A
authors.initials: VA
authors.lastname: Hadjimitova
authors.forename: Margarita N
authors.initials: MN
authors.lastname: Topashka-Ancheva
authors.forename: Denitsa B
authors.initials: DB
authors.lastname: Momekova
authors.forename: Trayko T
authors.initials: TT
authors.lastname: Traykov
authors.forename: Margarita H
authors.initials: MH
authors.lastname: Karaivanova
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects*; D015251:Epirubicin / Q000633:toxicity*; D004929:Esculin / Q000494:pharmacology*; D005609:Free Radicals / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D013481:Superoxides / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D005609:Free Radicals; D013481:Superoxides; D004929:Esculin; D015251:Epirubicin