Thalidomide may have been withdrawn in the early 1960s for use by pregnant women, but its dramatic effects remain memorable half a century later. Now, researchers have taken a major step toward understanding exactly how thalidomide causes the birth defects.
This is important as thalidomide is still used to treat diseases like multiple myeloma and leprosy, and is being tested for cancers and autoimmune disorders. This discovery was recently published online in the FASEB Journal (http://www.fasebj.org).
"The ability of thalidomide breakdown products to cause birth defects complicates our attempts to understand how the birth defects arise and the search for safer alternatives to thalidomide, although the rabbit embryo culture model will facilitate both processes," said Peter G. Wells, Pharm.D., a researcher involved in the work from the Department of Pharmacology and Toxicology at the University of Toronto in Ontario, Canada.
Specifically, Wells and colleagues found that birth defects result from not only thalidomide, but also from the compounds that it breaks down to in the body, which last up to 40 times longer in the body than thalidomide itself. These compounds ultimately lead to the production of highly toxic forms of oxygen, called "reactive oxygen species," (ROS) including hydrogen peroxide and free radicals that alter disrupt normal embryonic development, causing birth defects.
To make this discovery, the scientists developed a new animal model for fetal thalidomide exposure by extracting rabbit embryos from pregnant mothers during the first trimester of pregnancy, when the limbs and other structures are developing. Then they cultured the embryos in dishes for one to two days, with or without exposure to thalidomide or one of its breakdown products. Front and hind limb deformities as well as other abnormalities were observed only in the embryos exposed to thalidomide or one of its products. DNA damage caused by ROS and free radicals was similarly increased only in the exposed embryos.
"Administering thalidomide to pregnant women remains was of the biggest mistakes made in modern medicine," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "Yet we now use thalidomide and related products as effective therapies for serious diseases. This research not only explains what caused all that misery years ago, but promises to help us find safer alternatives to thalidomide in the future."
Receive monthly highlights from the FASEB Journal by signing up at http://www.faseb.org/fjupdate.aspx or you can like the Federation of American Societies for Experimental Biology on Facebook. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB) and celebrates its 25th anniversary in 2011. Over the past quarter century, the journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information.
FASEB comprises 23 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of scientists and engineers to improve—through their research—the health, well-being and productivity of all people. FASEB's mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.
Details: Crystal J. J. Lee, Luisa L. Gonçalves, and Peter G. Wells. Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)-dependent, reactive oxygen species (ROS)-mediated mechanism. FASEB J. doi:10.1096/fj.10-178814 ; http://www.fasebj.org/content/early/2011/04/15/fj.10-178814.abstract
Cody Mooneyhan | EurekAlert!
Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
On track to heal leukaemia
18.01.2017 | Universitätsspital Bern
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy