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Autoradiographic and tissue distribution studies on a nitrovinylfuran derivative (SQ 18506 14C) in S. mansoni
Abstract:
Autoradiographic and tissue distribution studies of SQ 18506 14C were carried out on 13 Swiss albino mice. Infection was done by I.P. route with 50 to 60 cercaria of S. mansoni (puerto Rican strain) per animal. The safe single i.v. dose of a solution containing one mg of SQ 18506 dissolved in 0.06 ml dimethylsulfoxide was 0.003 ml/g b.w. of mice. Schistosome autoradiograms were clearly demonstrated one day after that dose injected in each mouse 50 days post-infection. However, hepatic autoradiograms were visible 14 days after 2 doses of our drug to each infected mouse. The higher the concentration of SQ 18506 14C in the culture medium the darker were the schistosomes in the autoradiograms and the greater their total d.p.m/mg. Tissue distribution studies after 2 1/2 doses of our drug/mouse revealed that schistosome total d.p.m/mg dry-weight was 50 times more than that of its liver. The latter d.p.m/g wet-weight was slightly higher than that of one ml of mouse blood.
Insights
This study investigated the distribution of SQ 18506 14C in mice infected with Schistosoma mansoni. The drug concentrated in schistosomes, indicating potential for targeted therapy against schistosomiasis.
Area of Science:
- Pharmacology
- Parasitology
- Biomedical Imaging
Background:
- Schistosomiasis remains a significant global health concern, necessitating effective therapeutic agents.
- Understanding drug distribution is crucial for developing targeted treatments against parasitic infections.
Purpose of the Study:
- To evaluate the tissue distribution and autoradiographic localization of SQ 18506 14C in mice infected with Schistosoma mansoni.
- To assess the efficacy of SQ 18506 as a potential anti-schistosomal agent.
Main Methods:
- Autoradiography and tissue distribution studies were performed on Swiss albino mice infected with S. mansoni.
- Mice received varying doses of SQ 18506 14C via intravenous injection.
- Drug concentration and localization were determined using autoradiograms and d.p.m./mg measurements.
Main Results:
- SQ 18506 14C was clearly visualized in schistosomes one day post-injection, and in the liver after 14 days.
- Higher drug concentrations in vitro correlated with darker autoradiograms and increased d.p.m./mg in schistosomes.
- Tissue distribution studies revealed a 50-fold higher concentration of SQ 18506 14C in schistosomes compared to liver tissue.
Conclusions:
- SQ 18506 demonstrates significant accumulation in Schistosoma mansoni parasites within the host.
- The drug's preferential localization in schistosomes suggests its potential as a targeted therapeutic agent for schistosomiasis.
- Further research is warranted to explore the clinical application of SQ 18506 in treating schistosomiasis.