Carcinogenic Effects of Dual-Acting PPAR Agonists in Rats
Author Information
Author(s): Martin B. Oleksiewicz, Jennifer Southgate, Lars Iversen, Frederikke L. Egerod
Primary Institution: Novo Nordisk A/S
Hypothesis
The carcinogenic effect of dual-acting PPARα+γ agonists in the rat urothelium may be caused by receptor-mediated effects and off-target cytotoxic effects.
Conclusion
The study proposes a mode of action hypothesis for the carcinogenic effects of PPARα+γ agonists in rats, suggesting that these effects may be due to exaggerated pharmacology and cytotoxicity.
Supporting Evidence
- Chronic activation of PPARα is linked to cancer in rats and mice.
- PPARγ activation can also cause cancer in some cases.
- Urothelial cells express both PPARα and PPARγ, suggesting a potential mechanism for carcinogenicity.
- Previous studies have shown that certain PPAR agonists can induce bladder cancer in rats.
Takeaway
Some medications that activate certain receptors in rats can cause bladder cancer, and researchers are trying to understand why this happens.
Methodology
The study reviews existing literature and proposes a mode of action hypothesis based on previously published data and experimental findings.
Limitations
The hypothesis is speculative and based on available data, which may not fully represent the mechanisms involved in human carcinogenesis.
Digital Object Identifier (DOI)
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