Nitroxide malonate methanofullerene as biomimetic model of interaction of nitroxide species with antioxidants.

Bis-nitroxide malonate methanofullerene (NO)2-MF was studied as a biomimetic model of reduction-oxidation activity with natural compounds-cytochrome c (cyt c), dihydroquercetin (DHQ), ascorbic acid (AA) and synthetic drug-1-(ß-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine (xymedon(®)). (NO)2-MF may be used as the component of Langmuir monolayers on an aqueous subphase and as the adsorbate on silica gel. The activity of (NO)2-MF in the reaction with cyt c was compared with the effect of nitroxide species such as gaseous nitric oxide, 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) by using UV-vis and EPR-spectra. It has been shown, that iron(III) in cyt c(3+) under action (NO)2-MF was reduced up to iron(II), similar effect was observed under the influence of gaseous NO in aqueous solution, but reduction of iron(III) in heme cyt c was reversible in the presence of TEMPO. Therefore, the state of Fe-heme in cyt c can be used as the indicator of the interaction of cyt c with nitroxide species in vitro. The interaction of cyt c, DHQ, xymedon(®) with (NO)2-MF monolayers was confirmed by the increasing of limiting area А0 from 0.88 nm(2) up to 1.70 nm(2) of (NO)2-MF on the aqueous subphase, by the paramagnetism and UV-vis spectral data changes. These results can be explained by appearance of oxoammonium ion (NO(+))2-MF adlayers and monolayers. The antioxidant and regenerating effects were shown when treating wounds by xymedon(®) in the presence of additives (0.001%) of (NO)2-MF in the experiments on the rats.

The study of the complexes of nitromedicine with cytochrome c and NO-containing aqueous dosage form in the wound treatment of rats.

The interaction of cytochrome c with nitromedicines, such as 5-nitrofural, 5-nitroxoline, metronidazole and sodium nitrite which enables the generation of nitric oxide or nitrosyl complexes in the presence of ascorbic acid or sodium ascorbate in acid medium has been investigated. The pharmaceutical compositions containing cytochrome c and nitromedicine complexes as active substances were studied in the experiments by using rats. It has been shown that positive local and systemic effects were estimated when NO-containing gel was used at burn treatment. These positive effects at the local level are due to a sufficient microcirculation index which indicates intensification of the blood flow in the microvessels in the injured area. These effects at the systemic level provide maintenance of the general heart rhythm and gradual recovery of the vegetative balance which is not observed in the animals of the control group.