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Pyrvinium pamoate lacks in vivo genotoxicity in the colon
Abstract:
Pyrvinium pamoate, a widely used anthelmintic drug, has been previously tested for genotoxicity with equivocal results. Assays with bacterial or yeast test strains yielded positive results while in vitro tests with mammalian cells yielded negative results. In this study, the genotoxicity of pyrvinium was studied in vivo in the mouse colon, the therapeutic site of action of this agent. 1,2-Dimethylhydrazine (DMH), a colon carcinogen, was tested simultaneously as a positive control. The colonic nuclear aberration assay was used to determine genotoxicity. Pyrvinium delivered orally in three vehicles was not genotoxic in the murine colon, even at doses up to 12.5 times the recommended human dosage.
Insights
Pyrvinium pamoate, an anthelmintic drug, was evaluated for genotoxicity in the mouse colon. The drug did not demonstrate genotoxic effects in vivo, even at high doses, suggesting safety in the therapeutic context.
Area of Science:
- Pharmacology and Toxicology
- Gastrointestinal Health
- Genetics and Molecular Biology
Background:
- Pyrvinium pamoate is an established anthelmintic medication.
- Previous genotoxicity studies on pyrvinium pamoate yielded conflicting results, with positive findings in microbial assays but negative results in in vitro mammalian cell tests.
- The in vivo genotoxicity of pyrvinium pamoate, particularly at its site of action, remained unevaluated.
Purpose of the Study:
- To investigate the in vivo genotoxicity of pyrvinium pamoate in the mouse colon.
- To assess the safety profile of pyrvinium pamoate in its therapeutic target organ.
- To compare the in vivo genotoxicity with prior in vitro and microbial assay results.
Main Methods:
- The study utilized a colonic nuclear aberration assay in mice.
- Pyrvinium pamoate was administered orally using three different vehicles.
- 1,2-Dimethylhydrazine (DMH), a known colon carcinogen, was used as a positive control.
Main Results:
- Pyrvinium pamoate did not induce genotoxicity in the murine colon across the tested dose range.
- Even at doses 12.5 times the recommended human dosage, no significant colonic nuclear aberrations were observed.
- The positive control, DMH, exhibited expected genotoxic effects, validating the assay's sensitivity.
Conclusions:
- Pyrvinium pamoate is not genotoxic in vivo in the mouse colon.
- These findings resolve the equivocal results from previous genotoxicity studies.
- The study supports the safety of pyrvinium pamoate for its intended therapeutic use in treating helminth infections.