Nitric oxide and free stable nitroxyl radicals in the mechanism of biological action of the spin-labeled compounds.

A comparison of more important physical, chemical and biological properties of the nitric oxide (NO) and free stable nitroxyl radicals (nitroxides) on the base of their structural similarity is made in the article. The active moiety in the nitroxide molecule represents a sterically hindered nitric oxide. The mechanisms of biological action of the nitroxides and especially of their derivatives with antitumor agents from the groups of nitrogen mustards, nitrosoureas, aziridines and triazenes (spin-labeled compounds) is explained through the biological activities of sterically hindered NO. Similarly to NO, nitroxides also can react with superoxide anion radical (O(2)(-)), they possess superoxide dismutase (SOD) mimetic action. While the interaction of NO with O(2)(-)yields very toxic peroxynitrite (ONOO(-)), its formation is strongly limited in the presence of a nitroxide. It is known that the nitrosourea antitumor drugs, like lomustine (CCNU) and carmustine (BCNU), showed high general toxicity, one of the reasons for that probability is the formation of NO, and subsequently of ONOO(-), during their metabolism. The biological investigations of the nitroxides showed their considerably lower general toxicity that could be explained with the SOD-mimetic action of the nitroxide present in their molecule.

Inhibiting and disaggregating effect of gel-filtered Galega officinalis L. herbal extract on platelet aggregation.

The in vitro inhibiting and disaggregating effect on platelet aggregation of a gel-fractionated herbal extract from Galega officinalis L. is examined. The obtained Sephadex G-25 filtered fraction was 35-36 times more active than the crude extract. The threshold concentration at which this fraction inhibits platelet aggregation (5-10% inhibition) by 50 microM adenosine 5'-diphosphate (ADP) is 4.5-5 microg per 1 ml platelet-rich plasma (PRP). At a concentration of 35 microg/ml PRP the fraction inhibits 50% of aggregation by ADP and at a concentration of 125 microg/ml PRP fully inhibits the aggregation of PRP by ADP. At a concentration of 40 microg/ml PRP the fraction inhibits initiation of platelet aggregation by 0.18 mg/ml collagen and at 50 microg/ml PRP inhibits the initiation of aggregation by 0.7 units/ml thrombin. The G-25 filtered fraction shows a strong disaggregating effect on aggregated PRP. At a concentration of 65-75 microg/ml PRP, the fraction is able to disaggregate the 50-53% of aggregated platelet-rich plasma by 50 microM ADP, and 25% of aggregated PRP by 0.18 mg/ml collagen.

Inhibiting effect of desalted extract from Galega officinalis L. on platelet aggregation.

The inhibiting and disaggregating effect of desalted and fractionated herbal extract of Galega officinalis L. on platelet aggregation in vitro is studied. At a concentration of 35 micrograms/ml in a platelet-rich plasma (PRP) the fraction inhibits 50% of aggregation by ADP and at 125 micrograms/ml PRP it inhibits fully the aggregation of PRP by ADP. At a concentration of 40 micrograms/ml PRP the fraction inhibits the initiation of platelet aggregation by collagen and at 50 micrograms/ml PRP inhibits the initiation of aggregation by thrombin. At a concentration of 65 micrograms/ml PRP the fraction can disaggregate 50% of the aggregated platelet-rich plasma by ADP and 25% of aggregated PRP by collagen.