Echinococcus granulosus: in vitro effects of ivermectin and praziquantel on hsp60 and hsp70 levels.
Martinez, J., Perez-Serrano, J., Bernadina, W. E., Rodriguez-Caabeiro, F. 1999 Echinococcus granulosus: In vitro effects of ivermectin and praziquantel on hsp60 and hsp70 levels. Experimental Parasitology93, 171-180. Organisms or cells exposed to injurious stresses such as heat shock or chemicals respond by increased (or altered) expression of heat-shock proteins (HSPs). Conversely, an earlier exposure to stress can prepare cells to cope with a subsequent more severe stress. In the present study, protoscolices of Echinococcus granulosus were subjected to several anthelmintic treatments, involving storage of the protoscolices for 18, 30, and 50 h with 0.1 mg/ml of ivermectin (IV), praziquantel (PZ), and a combination of each with albendazole (ALB). The organisms were analyzed for the effects of drug treatment on cell integrity and on levels of hsp60 and hsp70 production. Drug efficacy was evaluated by microscopy and by protein content measurement. Hsp60 and hsp70 were detected by Western blotting and incubation with anti-hsp60 and anti-hsp70 antibody, respectively, and quantitation of these proteins was obtained using image analysis. Incubation with IV alone produced the most damage to the protoscolices as indicated by viability loss, decreased protein content, and altered hsp60 and hsp70 levels; incubation with IV + ALB produced less damage as manifested by fewer changes in the aforementioned damage parameters but PZ and PZ + ALB, in this context, were poor anthelmintics. Exposure of protoscolices to thermal stress prior to anthelmintic treatment, in most cases, increased drug efficacy. It is concluded that in the E. granulosus model system drug efficacy is associated with decreased levels of hsp70 expression and increased levels of hsp60 expression.
Martinez
J
J
Faculty of Pharmacy, Department of Microbiology and Parasitology, University of Alcala, 28871 Alcala de Henares, Madrid, Spain. francisco.martinez@alcala.es
Perez-Serrano
J
J
Bernadina
W E
WE
Rodriguez-Caabeiro
F
F
D015766:Albendazole / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D015153:Blotting, Western; D018834:Chaperonin 60 / Q000096:biosynthesis*; D004338:Drug Combinations; D004446:Echinococcus / Q000187:drug effects* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D007559:Ivermectin / Q000494:pharmacology*; D011223:Praziquantel / Q000494:pharmacology*
D000871:Anthelmintics; D018834:Chaperonin 60; D004338:Drug Combinations; D018840:HSP70 Heat-Shock Proteins; D011223:Praziquantel; D007559:Ivermectin; D015766:Albendazole