Fig. (8).

Ultrastructural changes observed in L. amazonensis after HIV PIs treatment. Parasites (108 cells) from 48-h cultures were inoculated in fresh medium in the absence (A) or in the presence of nelfinavir (B-H) or lopinavir (I-J) at the IC50 concentration, and incubated for 4 h (B-E), 6 h (F-G), 8 h (H) and 24 h (I-J). Subsequently, cells were processed for transmission electron microscopy. An intense flagellar and plasma membrane shedding (black arrowheads) was seen after 4 hours of treatment with both inhibitors (B-D). Some effects were exclusive of nelfinavir, such as cytoplasm shrink (B and E, ◈), increase in the number of intracellular vesicles, resembling acidocalcisomes (G, ★) and lipid inclusions (E and F, v). Both drugs induced nuclear wrapping by the endoplasmic reticulum (G and H, black arrows), mithocondrial swelling (F, white arrowheads) and myelin-like structures (H, larger arrow). In lopinavir treated cells, blocks of condensed chromatin were observed close to the nuclear envelope (I, white arrow), as well as enlarged vesicles (J, ✖). n - nucleus; k - kinetoplast; f - flagellum and m - mithocondrion. The ultrastructural alterations described for nelfinavir (B-H) were also visualized with lopinavir. Reprinted from PLoS One. 2009; 4(3): e4918. doi:10.1371/journal.pone.0004918.