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Mitochondria Are Targets for the Antituberculosis Drug Rifampicin in Cultured Epithelial Cells

M. V. Erokhina1,2*, A. V. Kurynina1, and G. E. Onishchenko1

1Lomonosov Moscow State University, Faculty of Biology, 119991 Moscow, Russia; fax: +7 (495) 939-4309; E-mail: masha.erokhina@gmail.com

2Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Yauzskaya Alley 2, 107564 Moscow, Russia; fax: +7 (499) 785-9108; E-mail: office_cniit@mail.ru

* To whom correspondence should be addressed.

Received March 25, 2013; Revision received May 23, 2013
Rifampicin is a widely used drug for antituberculosis therapy. Its target is the bacterial RNA polymerase. After entry into the human or mammalian organism, rifampicin is accumulated in cells of epithelial origin (kidneys, liver, lungs) where it induces apoptosis, necrosis, and fibrosis. The purpose of this study was to determine the intracellular mechanisms leading to rifampicin-induced pathological changes and cell death. We analyzed the survival and state of the chondriome of cultured epithelial cells of the SPEV line under the influence of rifampicin. Our data show that the drug induces pronounced pathological changes in the network and ultrastructure of mitochondria, and their dysfunction results in excessive production of reactive oxygen species and release of cytochrome c. These data suggest the initiation of the mitochondrial pathway of apoptosis. Simultaneously, we observed inhibition of cell proliferation and changes in morphology of the epithelial cells toward fibroblast-like appearance, which could indicate induction of epithelial–mesenchymal transition. Thus, mitochondria are the main potential target for rifampicin in cells of epithelial origin. We suggest that similar mechanisms of pathological changes can be induced in vivo in organs and tissues accumulating rifampicin during chemotherapy of bacterial infectious diseases.
KEY WORDS: rifampicin, fragmentation and pathology of mitochondria, oxidative stress, apoptosis

DOI: 10.1134/S0006297913100106