ROLE OF NITRIC OXIDE METABOLITES WITHIN THE IMPACT OF THE SUB-TOXIC SUCCINAMIDES DOSES ON STATE OF HEMOSTASIS.

We investigated the role of changes in the endogenous nitric oxide (NO) metabolism during the influence of succinic acid amides as biotransformation products of an anti-diabetic drug on the state of hemostasis. In experiment with rats, synthetic succinamides were applied in quanti- ties equimolar to the sub-toxic dose of the pharmaceutical substance. We investigated the indicators characterizing the state of platelet and coagulation hemostasis in the blood plasma, the content of the stable NO metabolites and the activity of nitrogen oxide synthase (NOS) in the liver homogenate, blood plasma and urine of rats. We found that sub-chronic succinamides introduction reduced the nitrite and nitrate anions concentration in the blood plasma (by 30-50 and 20-35% resp.), liver (by 16-19 and 14-18%) and urine (by 50-70 and 38-55%). These changes were essentially dependent on the reduction in the NOS activity (by 33%). The studied compounds showed a 1.5 fold increase in the coagulation potential of the blood plasma and cause a 20% boost in the aggregation of thrombocytes. Analysis of the pair correlation coefficients showed positive association of the changes in indicators of the NO metabolism and hemostasis. The obtained results suggest that the registered manifestation of the pro-coagulation and thrombogenic action of succinamides applied in the sub-toxic doses is partially determined by a drop of the vasoactive NO pool that in turn, occurs due to a decline of the NOS activity.

[The detection of the genotoxic and mutagenic activities of disperse azo dyes for their hygienic standardization]. / Vyiavlenie genotoksicheskoi i mutagennoi aktivnosti dispersnykh azokrasitelei s tsel'iu ikh gigienicheskogo normirovaniia.

Evaluating level and synthesis of DNA in liver cells, counting occurrence of dominant lethal mutations, the authors studied molecular and genetic effects of dispersed polyaether mononitrodyes Orange 2K and Red-Brown G after the peroral administration and the chronic inhalation (2.5 and 4 months). Red-Brown G examined in acute and chronic exposures appeared to be powerful mutagen. Orange 2K induced minor changes of nuclear DNA functioning in liver cells, if compared to Red-Brown G. In Dominant Lethal Mutations Test both dyes were assigned to mild mutagens. The diagnosed effects are used for setting hygienic standards in the air of workplace.