title: Biotransformation and nitroglycerin-induced effects on antioxidative defense system in rat erythrocytes and reticulocytes.
abstract: The effects of nitroglycerin (glyceryl trinitrate - GTN) are mediated by liberated nitric oxide (NO) and formed reactive nitrogen species, which induces oxidative stress during biotransformation in red blood cells (RBCs). The aim of this study was to evaluate effects of GTN on antioxidative defense system (AOS) in rat erythrocytes (without) and reticulocytes (with functional mitochondria). Rat erythrocyte and reticulocyte-rich RBC suspensions were aerobically incubated (2 h, 37°C) without (control) or in the presence of different concentrations of GTN (0.1-1.5 mM). After incubation, concentrations of non-enzymatic components of AOS, activities of antioxidative enzymes and oxidative pentose phosphate (OPP) pathway activity were followed in RBC suspensions. In rat reticulocytes, GTN decreased the activity of mitochondrial MnSOD and increased the activity of CuZnSOD. In rat RBCs, GTN induced increase of Vit E concentration (at high doses), but decreased glutathione content and activities of all glutathione-dependent antioxidative enzymes; the OPP pathway activity significantly increased. GTN biotransformation and induction of oxidative stress were followed by general disbalance of antioxidative capacities in both kinds of RBCs. We suggest that oxidative stress, MnSOD inhibition and depletion of glutathione pool in response to GTN treatment lead to decreased bioavailability of NO after GTN biotransformation in rat reticulocytes.
authors.affiliation: Department for Biology and Ecology, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia. smarkovic@kg.ac.rs.
authors.forename: Snežana D
authors.initials: SD
authors.lastname: Marković
authors.forename: Nataša Z
authors.initials: NZ
authors.lastname: Dorđević
authors.forename: Milena G
authors.initials: MG
authors.lastname: Curčić
authors.forename: Andraš S
authors.initials: AS
authors.lastname: Stajn
authors.forename: Mihajlo B
authors.initials: MB
authors.lastname: Spasić
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D005996:Nitroglycerin / Q000378:metabolism* / Q000494:pharmacology*; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D051381:Rats; D012156:Reticulocytes / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005996:Nitroglycerin