Oesophagostomum dentatum: effect of glutathione S-transferase (GST) inhibitors on GST activity and larval development.
Sulphobromophthalein (SBP) inhibits isolated glutathione S-transferase of the porcine nodule worm Oesophagostomum dentatum (Od-GST) and reduces larval development in vitro. In this study possible inhibitory effects of various inhibitors were evaluated in an enzymatic (CDNB) assay with isolated Od-GST and in a larval development assay (LDA). Reversibility was tested in the LDA by removing the inhibitor from culture halfway through the cultivation period. SBP, indomethacin and ethacrynic acid inhibited both enzyme activity and larval development in a dose-dependent and reversible manner. HQL-79 also reduced larval development but had only a minor effect on the isolated enzyme. The phospholipase A(2) inhibitors dexamethasone and hydrocortisone had no major effect. High thermal stability of Od-GST was demonstrated with increasing activity between 4 and 50°C. Differences between Od-GST and GST of other organisms indicate structural and possibly functional peculiarities and highlight the potential of such enzymes as targets of intervention.
Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, A-1210 Vienna, Austria. Anja.Joachim@vetmeduni.ac.at
Anja
A
Joachim
Esther
E
Lautscham
Jana
J
Christoffers
Bärbel
B
Ruttkowski
D000818:Animals; D001681:Biological Assay; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology; D005260:Female; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007420:Intestine, Large / Q000469:parasitology; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D054834:Lipocalins / Q000037:antagonists & inhibitors; D008297:Male; D009815:Oesophagostomum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D010880:Piperidines / Q000494:pharmacology; D013448:Sulfobromophthalein / Q000494:pharmacology; D013552:Swine; D013696:Temperature
C116322:4-benzhydryloxy-1-(3-(1H-tetrazol-5-yl-)-propyl)piperidine; D004791:Enzyme Inhibitors; D054834:Lipocalins; D010880:Piperidines; D013448:Sulfobromophthalein; D003907:Dexamethasone; D005982:Glutathione Transferase; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D004976:Ethacrynic Acid; D006854:Hydrocortisone; D007213:Indomethacin