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High death rate in mice treated topically with diclofenac
Catharina M Lerche1, Peter A Philipsen, Thomas Poulsen
1Department of Dermatology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, Copenhagen, Denmark. Cler0001@bbh.regionh.dk
Experimental Dermatology
|March 4, 2011
Summary
Topical diclofenac gel, used for actinic keratoses, significantly reduced survival in mice exposed to simulated solar radiation. This study found severe gastrointestinal side effects, not linked to ingestion, leading to early experiment termination.
Area of Science:
- Dermatology
- Toxicology
- Photobiology
Background:
- 3% diclofenac sodium gel is a new treatment for actinic keratoses.
- Limited data exists on the photocarcinogenesis of topical diclofenac.
- The potential for topical diclofenac to accelerate photocarcinogenesis requires investigation.
Purpose of the Study:
- To investigate if topical diclofenac accelerates photocarcinogenesis.
- To assess the safety and side effects of topical diclofenac under simulated solar radiation (SSR).
Main Methods:
- Hairless mice received topical diclofenac three times weekly.
- Mice were exposed to ultraviolet radiation (2, 3, or 4 SED) until death.
- Gastrointestinal side effects were monitored, with some mice fitted with Elizabethan collars to prevent ingestion.
Main Results:
- Diclofenac treatment significantly reduced mouse survival (P<0.0001).
- Observed side effects included peptic ulcers, esophageal ulcers, and gastrointestinal bleeding.
- Mice experienced discomfort and weight loss, leading to experiment termination after 151 days.
Conclusions:
- Topical diclofenac, under SSR, caused significant mortality and severe gastrointestinal toxicity in mice.
- The observed gastrointestinal side effects were not solely due to oral ingestion.
- Further research is needed to understand the risks associated with topical diclofenac, especially with UV exposure.
