The effect of praziquantel treatment on glutathione concentration in Schistosoma mansoni.
A fluorescent dye monochlorobimane (MCB) that binds glutathione (GSH) was used as a tool for measuring the concentration of GSH in skin and mechanically-transformed schistosomula. The specificity of MCB binding to GSH was confirmed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The MCB binding to GSH is an energy-dependent process since no labelling could be seen at low temperature. When 24-h-old schistosomula were depleted of GSH by buthionine sulfoximine (a specific inhibitor of GSH synthesis) for 18 h, a significant decrease (P < 0.001) in fluorescence was observed. PZQ treatment of the schistosomula after first labelling the parasites with MCB did not greatly affect MCB binding to GSH. However, when the 24-h-old schistosomula were first PZQ treated and afterwards labelled with MCB, the pattern of labelling was identical to that of those of the non-labelled parasites. When 24-h-old schistosomula were first PZQ treated, washed and labelled in the presence of 1 mM GSH, the level of fluorescence was recovered. These results suggest that PZQ depletes GSH from schistosomula, and may render them susceptible to the host's immune system.
Ribeiro
F
F
Department of Biochemistry and Molecular Biology, IBLS, Glasgow University, UK. gbca66@ucdf.gla.ac.uk
Coelho
P M
PM
Vieira
L Q
LQ
Watson
D G
DG
Kusel
J R
JR
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000494:pharmacology*; D015415:Biomarkers; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D051379:Mice; D008856:Microscopy, Fluorescence; D011223:Praziquantel / Q000494:pharmacology*; D011647:Puerto Rico; D011720:Pyrazoles / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012908:Snails / Q000469:parasitology
D000980:Antiplatyhelmintic Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D011720:Pyrazoles; D019328:Buthionine Sulfoximine; D011223:Praziquantel; C059597:monochlorobimane; D005982:Glutathione Transferase; D005978:Glutathione