The schistosomicidal compound Ro 15-5458 causes a reduction in the RNA content of Schistosoma mansoni.
The effect of Ro 15-5458 (10-2-(diethylamino)ethyl-9-acridanone(2-thiazolin- 2-yl)hydrazone) on the steady-state RNA levels of Schistosoma mansoni was studied after dosing the host with 15 mg kg-1 and retrieving parasites. Total RNA content of parasites recovered from the host 12, 72 and 96 h after dosing was reduced by 14, 30 and 41%, respectively. Quantitative filter hybridization of blots of RNA extracted from treated and control parasites with specific probes indicated a decline in actin and superoxide dismutase mRNA as well as rRNA of treated parasites. The decline was observed 12 h after dosing, 48 h before parasites showed drug-induced changes in other vital biological processes. A prominent drug-induced reduction was seen on the 1.9 kb actin mRNA compared to the 1.4 kb. The same dose of the drug did not alter the actin mRNA content of the host liver. Similarly, the administration of the inactive structural analogue Ro 21-6787 (10-2-(diethylamino)ethyl-9-acridanone) was without any effect. We propose that the actions of Ro 15-5458 and/or its products are directed towards the inhibition of the expression of parasite genes.
Eshete
F
F
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Bennett
J L
JL
D000166:Acridines / Q000494:pharmacology*; D000199:Actins / Q000235:genetics; D000818:Animals; D003720:Densitometry; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D012339:RNA, Ribosomal, 28S / Q000378:metabolism; D012550:Schistosoma mansoni / Q000187:drug effects / Q000235:genetics*; D012556:Schistosomicides / Q000494:pharmacology*
D000166:Acridines; D000199:Actins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D012339:RNA, Ribosomal, 28S; D012556:Schistosomicides; C062730:Ro 15-5458