E.S. Baeva, V.G. Artyukhov

The thesis discusses the results of research of the influence of fluoroquinolones on the structural state of human endoglobular haemoglobin. Emphasis was made on fluoroquinolones having different non-antibacterial effects that facilitate the therapy of inflammatory processes. The fluoroquinolones are known as low-toxic substances. In general, the common side-effects are mild to moderate and self-limiting. Fluoroquinolone phototoxicity is caused by the generation of toxic free oxygen species under exposure to excessive insolation. It has been established that fluoroquinolones have the promoting effect on phagocytic activity of polynuclears and macrophages, and they can substantially increase the formation of hydrogen peroxide by the leucocytes. It was demonstrated in our previous investigations that fluoroquinolones modify cytoplasmic skeleton of erythrocytes and induce their hemolytic efficiency. It was also revealed that the fluoroquinolones have a certain affinity to endoglobular haemoglobin. Based on the analysis of data obtained in our laboratory, and on the cited authorities, the thesis concludes that the problem of rational antibiotic therapy is a pressing one and requires further research in this field. We have been able to demonstrate, with the use of absorption spectrophotometry, that fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin), by entering endoglobular cells, chemically modify haemoglobin molecules. It has been established that antibiotics being studied affect haemoglobin in a similar way. We have made an assumption that fluoroquinolones weaken the link between the haeme group and the ligand (oxygen). Possible mechanisms of their action are under consideration. It was found that the nature of effect of the modifier depends on its chemical structure and concentration in the incubation medium. Such dependence of the level of activity of antibiotics on concentration allowed us to conclude that structural modifications of one of the components of haemoglobin can directly or indirectly affect its other component. The thesis demonstrates that molecular complexes of the examined antibiotics with oxyhaemoglobin facilitate the decrease of the level of methemoglobin in the cell and, thus, protect it. The highest decrease of the level of methemoglobin was revealed in cells after the action of ofloxacin, the lowest one was established in erythrocytes using sparfloxacin in both concentrations.