Oxamniquine, praziquantel and lovastatin association in the experimental Schistosomiasis mansoni.
The activity of lovastatin associated with oxamniquine or praziquantel against schistosomiasis mansoni was evaluated in mice infected with Schistosoma mansoni. Forty days after infection, mice were treated with lovastatin, 400 mg/kg for five consecutive days by oral route, and on the last day of this sequence with 50 mg/kg oxamniquine or with 200 mg/kg praziquantel, both by oral route, single dose. Fifteen days later, the animals were perfused in parallel with an untreated control group. Studies were carried out in vitro, using lovastatin in culture medium containing S. mansoni worms proceeding from experimentally infected mice. In the in vivo trials, the association of lovastatin with oxamniquine or praziquantel did not show any additive action, but there were oogram changes when lovastatin was associated with oxamniquine. In vitro lovastatin was able to interrupt the maturation of S. mansoni eggs, which remained at the 1st or 2nd stages, depending on the dose used. The total number of morphologically dead eggs found in culture of worms exposed to 2 microg/ml or 4 microg/ml concentrations of lovastatin was significantly higher than the number of viable eggs. Using the probe Hoescht 33258 it was observed that 70% of the eggs considered morphologically viable in the treated groups (against 16% in the control group) were labeled, indicating that the majority of the viable eggs had membrane permeability increased due to lovastatin action.
Araújo
Neusa
N
Laboratório de Esquistossomose, Instituto René Rachou, Fiocruz, Belo Horizonte, MG, Brasil. araujon@cpqrr.fiocruz.br
Mattos
Ana Carolina Alves de
AC
Sarvel
Ana Karine
AK
Coelho
Paulo Marcos Zech
PM
Katz
Naftale
N
D000818:Animals; D004359:Drug Therapy, Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008148:Lovastatin / Q000627:therapeutic use*; D051379:Mice; D010073:Oxamniquine / Q000627:therapeutic use; D011223:Praziquantel / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000201:enzymology; D012555:Schistosomiasis mansoni / Q000188:drug therapy*; D012556:Schistosomicides / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012556:Schistosomicides; D010073:Oxamniquine; D011223:Praziquantel; D008148:Lovastatin