[Inhibition of oxidative phosphorylation in Crithidia fasciculata and Trypanosoma cruzi by lipophilic o-quinones and nifurtimox].
ATP and ADP levels were determined in Crithidia fasciculata and Trypanosoma cruzi. The nucleotide levels in crithidia or epimastigotes at the stationary phase of growth were, in nmol/10(8) cells, 15-40, and 3-7, for ATP and ADP, respectively. Incubation with the lipophilic o-naphthoquinones CG 8-935, CG 9-442 and CG 10-248 or the anti-chagasic nitrofuran nifurtimox, significantly decreased ATP level, with non-significant variations of the ADP level. The kinetics of ATP variation showed an initial 1-2 h lag and the diminution of the ATP level reached maximum value after 4-6 h incubation. Addition of L-glutamate or D-glucose as energy sources produced 2- or 3-fold increase of ATP level, after incubation the protozoa for 4-6 h with the corresponding substrates. Quinones and nifurtimox strongly depressed D-glucose or L-glutamate effects. Buthionine sulfoximine an inhibitor of glutathione biosynthesis, enhanced the effect of nifurtimox on ATP level in Crithidia fasciculata. It is concluded that by inhibiting ATP synthesis, either directly or-through oxygen radicals, the assayed drugs produced their cytotoxic action.
Biscardi
A M
AM
Centro de Investigaciones Bioenergéticas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Fernandez Villamil
S H
SH
Stoppani
A O
AO
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016831:Crithidia fasciculata / Q000187:drug effects* / Q000378:metabolism; D009285:Naphthoquinones; D009547:Nifurtimox / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
D009285:Naphthoquinones; D011809:Quinones; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009547:Nifurtimox
Inhibición de la oxidación fosforilante en Crithidia fasciculata y Trypanosoma cruzi por o-quinonas lipofílicas y nifurtimox.