The in vivo antifungal activity of the
naphthoquinone beta-lapachone against disseminated
infection by Cryptococcus neoformans was investigated. Swiss mice were immunosuppressed daily with
dexamethasone (0.5 mg per mouse) intraperitoneally for 3 days, the procedure was repeated 4 days later, and the animals were then challenged intravenously with C. neoformans (10(6) CFU/mL) 1 week later. Seven days after
infection, the mice were divided into groups and treated daily with
beta-lapachone (10 mg/kg, iv) for 7 (N = 6) and 14 days (N = 10).
Amphotericin B (0.5 mg/kg) was used as comparator
drug and an additional group received PBS. Treatment with
beta-lapachone cleared the yeast from the spleen and liver, and the fungal burden decreased approximately 10(4) times in the lungs and brain 14 days after
infection when compared to the PBS group (P < 0.05). This result was similar to that of the
amphotericin B-treated group. Protection was suggestively due to in vivo antifungal activity of this
drug and apparently not influenced by activation of the immune response, due to similar leukocyte cell counts among all groups. This study highlights the prospective use of
beta-lapachone for treatment of disseminated
cryptococcosis.