Protective qualities of mitochondrial and cytosolic fluorescent dyes against in vitro and in vivo infection by the Tulahuen strain of Trypanosoma cruzi.
This study demonstrates the binding of various fluorescent dyes (3,3' dihexyloxacarbocyanine iodide [DiOC6I], doxycycline [DOTC], rhodamine 123, and merocyanine 540) to infectious and intracellular forms of the Tulahuen strain of Trypanosoma cruzi. These dyes predominantly localize in mitochondria. Following treatment with DiOC6I and DOTC, both irradiated and nonirradiated samples showed dark toxicity to T. cruzi, whereas the other dyes effected toxicity only following irradiation with light. Under in vitro conditions, 91% protection was obtained 96 hr postinfection under dark conditions through the use of 0.573 micrograms/ml of DiOC6I. During in vivo studies, the onset of parasitemia was delayed by 7 days through the use of DiOC6I in ng/ml levels. Host deaths occurred in the infected control group on day 11 postexposure, whereas in the 5.7-ng/ml dye-treated group, no death had occurred after 20 days postexposure. This study demonstrates delay of onset of T. cruzi infections with the use of DiOC6I at concentrations well below the levels toxic to the host.
Dennis
M V
MV
Baylor Research Foundation, Dallas, Texas 75246.
Judy
M M
MM
Matthews
J L
JL
Sogandares-Bernal
F
F
D000818:Animals; D002232:Carbocyanines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy; D003600:Cytosol / Q000378:metabolism*; D004318:Doxycycline / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism*; D011744:Pyrimidinones / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D013050:Spectrometry, Fluorescence; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D005456:Fluorescent Dyes; D011744:Pyrimidinones; D012235:Rhodamines; D020112:Rhodamine 123; C003954:merocyanine dye; D004318:Doxycycline