Biotransformation and nitroglycerin-induced effects on antioxidative defense system in rat erythrocytes and reticulocytes
2014
Authors:
Marković, Snežana D.Đorđević, Nataša Z.
Ćurčić, Milena G.
Štajn, Andraš Š.
Spasić, Mihajlo
Document Type:
Article (Published version)
,
© 2014 Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences
Metadata
Show full item recordAbstract:
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
degrees 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.
Keywords:
Antioxidative defense system; MnSOD; Nitric oxide; Nitroglycerin; Red blood cellsSource:
General Physiology and Biophysics, 2014, 33, 4, 393-401Funding / projects:
- Preclinical investigation of bioactive substances (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41010)
- Molecular and physiological biomonitoring of aerobic organisms based on the determination of biochemical biomarkers of oxidative stress (RS-MESTD-Basic Research (BR or ON)-173041)
DOI: 10.4149/gpb_2014018
ISSN: 1338-4325