Analysis of the Efficiency of Different Antituberculous Drugs and Approaches to Treat BCG-Induced Granulomatosis in Mice and Abundance and Localization of Mycobacterium tuberculosis in the Liver.

In 3 months after infection with Mycobacterium tuberculosis (MBT) from BCG vaccine, male BALB/с mice received intraperitoneal injections of isonicotinic acid hydrazide, dextrazide, or liposome-encapsulated dextrazide, or inhalation of liposome-encapsulated dextrazide 2 times a week for 6 months. In 6 months, no MBT were detected in macrophages outside granulomas in treated mice. Macrophages containing MBT can incorporate into granulomas and leave them after suppression of MBT persistence. Liposome-encapsulated dextrazide showed the maximum therapeutic efficiency: the total MBT level in granuloma macrophages and volume density of destruction foci in the liver parenchyma decreased by 5.1 and 5.3 times, respectively, in comparison with the corresponding parameters in mice treated with isonicotinic acid hydrazide. Inhalations of liposome-encapsulated dextrazide prevented the destructive processes in liver granulomas due to macrophage migration from granulomas, which reduced granuloma sizes and destructive potential of granuloma lysosomes and therefore improved their diffusion-dependent trophics.

Location of Pulmonary Mycobacteria Tuberculosis and Effectiveness of Various Dextrazide Compositions in Treatment of Mice with BCG-Induced Granulomatosis.

The study examined effectiveness of liposomal form of dextrazide (inhaled or intraperitoneal), free dextrazide (intraperitoneal), and isoniazid (intraperitoneal) in the treatment of BALB/c mice with BCG-induced granulomatosis. The mice were infected with mycobacteria tuberculosis 3 months prior to onset of treatment. The preparations under examinations were administered twice a week over 2 months. The decrease of the number and size of macrophagal granulomas in mice BCG-induced granulomatosis during treatment was determined by the number of living mycobacteria tuberculosis in these granulomas. The most effective treatment was achieved with liposomal form of dextrazide (a conjugate of oxidized dextran with isonicotinic acid hydrazide). Macrophages with captured mycobacteria tuberculosis, dextrazide, and dextrazide-loaded liposomes can be incorporated into granulomas. The antimycobacterial effect of dextrazide is an important factor preventing the destructive processes in granulomas and organs via a decrease in the prodestructive potential of lysosomes in macrophages realized after their migration from granulomas.