Direct EPR Detection of Nitric Oxide in Mice Infected with the Pathogenic Mycobacterium Mycobacterium tuberculosis

Abstract

It has been shown that treatment of mice preinfected with Mycobacterium tuberculosis with spin NO traps (iron complexes with diethyldithiocarbamate) enables detection of large amounts of NO in internal organs 2 and 4 weeks after infection (up to 55–57 μmol/kg of wet lung tissue accumulated with spin NO traps during 30 min). The animals were infected with the drug-sensitive laboratory strain H37Rv and a clinical isolate nonrespondent to antituberculous drugs (the multidrug-resistant strain of M. tuberculosis) obtained from a patient with an active form of tuberculosis. Two weeks after infection with the multidrug-resistant strain, the NO level in the lungs, spleen, liver and kidney increased sharply concurrently with slight lesions of lung tissue. A reverse correlation, i.e., low level of NO in the lungs and other internal organs and extensive injury of lung tissue, was established for H37Rv-infected mice. Four weeks after infection, NO production in the lungs increased dramatically for both M. tuberculosis strains resulting in 80–84% damage of lung tissue. The lesion is suggested to be due to the development of defense mechanisms in M. tuberculosis counteracting NO effects.