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

Bull Exp Biol Med. 2020 May;169(1):63-66. doi: 10.1007/s10517-020-04825-6. Epub 2020 Jun 3.

Abstract

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.

Keywords: BCG-induced granulomatous tuberculosis; dextrazide in liposomes; inhalation; mice; mycobacteria tuberculosis.

MeSH terms

  • Animals
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / therapeutic use*
  • BCG Vaccine / adverse effects*
  • Dextrans / chemistry
  • Dextrans / therapeutic use*
  • Drug Combinations
  • Granuloma, Respiratory Tract* / chemically induced
  • Granuloma, Respiratory Tract* / drug therapy
  • Granuloma, Respiratory Tract* / etiology
  • Granuloma, Respiratory Tract* / microbiology
  • Isoniazid / analogs & derivatives
  • Isoniazid / chemistry
  • Isoniazid / therapeutic use*
  • Lung / drug effects
  • Lung / microbiology*
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Mycobacterium tuberculosis / physiology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / pathology
  • Tuberculosis, Pulmonary / prevention & control

Substances

  • Antitubercular Agents
  • BCG Vaccine
  • Dextrans
  • Drug Combinations
  • dextrazide
  • Isoniazid