Trypanocidal effect of SKF525A, proadifen, on different developmental forms of Trypanosoma cruzi.
SKF525A, an inhibitor and inducer of cytochrome P450, was tested on different developmental stages of Trypanosoma cruzi. Growth, motility and structure of epimastigotes, motility and infectivity of trypomastigotes, and infectivity of trypomastigotes to Vero cells in culture were abolished by the drug at 10-100 microM concentrations. When blood from infected mice was treated with the drug, and used to infect 8 day-old mice, no parasites were observed at 0.6-1 mM, and all animals survived. Blood cell morphology was well preserved, and the sleeping time of pentobarbital-treated mice inoculated with the same amount of drug was not increased. The present results suggest that SKF525A or other related inhibitors of cytochrome P450 coned be tested as an additive for blood sterilization in blood banks.
Franke De Cazzulo
B M
BM
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín, Argentina. jcazzulo@inti.gov.ar
Bernacchi
A
A
Esteva
M I
MI
Ruiz
A M
AM
Castro
J A
JA
Cazzulo
J J
JJ
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010424:Pentobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology*; D013997:Time Factors; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D014709:Vero Cells / Q000187:drug effects
D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D010424:Pentobarbital