23 June 2017 |       Share
 
 
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SAFETY ASSESSMENT AND ENVIRONMENTAL TOXICOLOGY

While designing a compound for a precise goal (e.g. efficacy towards a distinct molecular target or a condition) is a hypothesis-driven process, toxicology deals with unexpected - and often deleterious - effects. In vivo imaging, offering a general view of the whole organism, is the ultimate tool for the unbiased observation-based research.


DRUG SAFETY

Long-term treatments may reveal unintended, potentially harmful effects.

In this example ERE-Luc repTOP™ mice were treated for three weeks with Tamoxifen. As expected, in the first days of treatment, estrogen receptors are activated in the liver. But, unexpectedly, this effect disappears with time, and receptors are activated in the gut. This observation should prompt a deeper investigation for excluding potential toxic effects in the intestine.

 

REPORTER MICE ARE A POWERFUL TOOL FOR PINPOINTING ORGANS AT RISK OF TOXIC EFFECTS


TOXICITY EXPLORED DURING GESTATION AND LACTATION

Either for candidate drugs or chemical contaminants (like p,p’-DDT), with repTOP™ mice it is possible to study toxic effects not only in the different organs of adults, but also during gestation and lactation.

This examples shows how, by in vivo imaging, it is possible to follow estrogen receptor activity in embryos in the repTOP™ ERE-Luc model (numbers refer to days of pregnancy).





Left panel: Adult ERE-Luc repTOP™ mice were treated with DDT (dark blue bars) or with vehicle (light blue bars). Luciferase activity was measured in extracts of liver and brain after 16 hours.

Right panel: Lactating mothers were treated with the same compound (dark blue bars) or vehicle (light blue bars) at day 4 after delivery. Suckling pups were sacrificed 16 hours later and luciferase activity was measured as for adult mice.


REFERENCES

OTHER APPLICATIONS

repTOP™ mice can be applied also to the study of

* Drug discovery
* Nutraceuticals and functional food