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• W2368072868 abstract "To observe and compare the inhibition of hemozoin formation and the in vitro as well as in vivo antischistosomal activity induced by seven antimalarial drugs.Inhibition of hemozoin formation displayed by chloroquine phosphate, quinine hydrochloride, quinidine, mefloquine hydrochloride, pyronaridine phosphate and lumefantrine at 25 micromol/L, and artemether at 100 micromol/L was performed by assay of inhibition of beta-hematin formation in 1 mol/L sodium acetate buffers containing hematin with various pH of 4.0, 4.2, 4.4, 4.6, 4.8, and 5.0. In in vitro antischistosomal study, the medium of RPMI 1640 supplemented by 10% calf serum was used to maintain the adult Schistosoma japonicum, and the 50% and 95% lethal concentrations (LC50 and LC95) to kill the adult worms of each drug were then determined. Meanwhile, the interaction of quinine, pyronaridine and chloroquine combined with hemin against adult schistosomes was also undertaken. As to in vivo test, the efficacy of seven antimalarial drugs administered orally or intraperitoneally to mice infected with adult schistosomes was observed.In the acidic acetate-hematin solution, 25 micromol/L pyronaridine showed significant inhibition of beta-hematin formation at pH 4.4-5.0 with inhibition rates of 81.3%-97.0%. At pH 4.6, the inhibition rates of beta-hematin formation in acetate-hematin solution induced by mefloquine, chloroquine or quinine at concentration of 25 beta mol/L were 79.7%, 72.8% or 65.8%, respectively, and the beta-hematin formation was continually inhibited by these 3 antimalarial drugs at pH 4.8 and 5.0 with inhibition rates of 83.1%-90.6%, 41.9%-49.0% or 53.2-62.0%. The inhibition rates of beta-hematin formation at pH 4.6 and 4.8-5.0 induced by lumefantrine 25 micromol/L were 74.3% and 40.4%-40.5%, respectively. While under the same concentration of quinidine, 53.4% and 50.9% inhibition rates of beta-hematin formation were observed at pH 4.8 and 5.0. As to artemether, higher concentration of 100 micromol/L only showed light inhibition of beta-hematin formation at pH 4.4-4.8 with inhibition rates of 16.6%-25.0%. As regard to in vitro test, the LC50 and LC95 of mefloquine, pyronaridine, quinine and quinidine were 4.93 and 6.123 microg/ml, 37.278 and 75.703 microg/ml, 93.688 and 134.578 microg/ml, as well as 101.534 and 129.957 microg/ml, respectively. When adult schistosomes were exposed to the medium containing chloroquine, lumefantrine or artemether at higher concentrations of 100 or 120 microg/ml for 72 h, no or only individual worms died. Hence the LC50 and LC95 of these 3 drugs could not be determined. In other in vitro test, adult schistosomes exposed to quinine 50 micromol/L (20 microg/ml) in combination with 153.4 micromol/L (100 microg/ml) hemin, all worms died within 72 h post incubation. While the worms exposed to 50 micromol/L (26 microg/ml) chloroquine combined with the same concentration of hemin, only 18.8%(3/16) of worm died at 72 h post exposure. Unexpectedly, in schistosomes exposed to pyronaridine at a toxic concentrations of 50 micromol/L (46 microg/ml) in combination with 153.4 mol/L (100 microg/ml) hemin for 72 h, all of the worms were protected from the toxic action induced by pyronaridine, which revealed in normal motor activity and appearance of morphology in majority of the worms. In in vivo test, mice infected with adult schistosomes were treated orally with chloroquine, pyronaridine or lumefantrine at a daily dose of 400 mg/kg for 3 days, or intraperitoneally with chloroquine or pyronaridine at a daily dose of 100 mg/kg for 2 or 3 days, no apparent efficacy was seen. When mefloquine, quinine, quinidine or artemether were administered orally to infected mice at a single dose of 400 mg/kg or 200 mg/kg (mefloquine), all groups of mice treated showed moderate or higher efficacy with worm burden reductions of 61.1%-98.1%.Among the seven antimalarial drugs tested, their inhibitions of hemozoin (beta-hematin) exhibit no definite correlation to their in vitro and in vivo antischistosomal activity. Quinine in combination with hemin shows synergistic effect against schistosomes in vitro. While antagonist effect is observed in pyronaridine combined with hemin." @default.
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• W2368072868 date "2013-06-01" @default.
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• W2368072868 title "[Comparative observation on inhibition of hemozoin formation and their in vitro and in vivo anti-schistosome activity displayed by 7 antimalarial drugs]." @default.
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