[Effects of molsidomine on changes in oxidant/antioxidant status of rat erythrocytes].
BACKGROUND
Molsidomine (MO) is an established drug in treatment of coronary heart disease. Considering that MO is a donor of nitric oxide (NO) and a superoxide anion radical (O2*-), which forms peroxynitrite, a very toxic radical, the aim of this study was further elucidation of molecular mechanisms of MO action, particularly effects on prooxidative-antioxidative status of rat erythrocytes.


METHODS
Rat (Wistar albino, male, 250-300 g of b.m.) erythrocyte suspensions were aerobically incubated (120 min, 37 degrees C) without (control) or with MO (0.1, 0.25, 0.5, 1.0 and 1.5 mM). Concentrations of reactive oxygen species, methemoglobin, Heinz bodies, lipid peroxides, vitamins and glutathione, as well as activities of enzymes of the antioxidative defense system (AOS) were evaluated using standard techniques.


CONCLUSIONS
Molsidomine increases nitrite concentrations (indicating NO+ level), hydroxylamine (indicating NO- level), 3-nitro-tyrosine (indicating ONOO- level) and H2O2, but decreases O2*- level in a dose-dependent manner (changes are statistically significant only with high doses of molsidomine--1.0 and 1.5 mM). These alterations were followed by partial cells damage, increased formation of Heinz bodies, but there were no changes in MetHb and lipid peroxide levels. The defense response of erythrocytes to evident oxidative stress includes increased Vitamin E and Vitamin C concentrations (nonenzymatic components ofAOS), as well as decreased glutathione (reduced and oxidized) levels. Activities ofAOS enzymes remain unchanged.


CONCLUSIONS
Experimental doses of MO induce oxidative stress in rat erythrocytes. However, the first line of AOS is successful in the cellular defence response.
Maletić
Snezana D
SD
maletic@knez.uis.kg.ac.yu
Ognjanović
Branka I
BI
Stajn
Andras S
AS
Zikić
Radoslav V
RV
Spasić
Mihailo B
MB
Saicić
Zorica S
ZS
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D000975:Antioxidants; D020030:Nitric Oxide Donors; D016877:Oxidants; D014665:Vasodilator Agents; D008981:Molsidomine