Free radicals in mechanical trauma to the muscle. Identification of the contributing species, mechanisms of their formation, and their effects on metabolic and immunologic functions

• Applicant: Professor Dr. Herbert de Groot, since 10/2009 (†)
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2008 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 68338862

Free radicals crucially contribute to a great variety of cell and tissue injurious processes, but also possess fundamental physiological functions. We want to elucidate the role free radicals are playing in blunt muscle trauma, a type of injury especially occurring as a result of severe crush accidents. In the current period of the project we demonstrated that reactive oxygen species (ROS) are formed immediately upon disruption of cultured skeletal myocytes. We were able to identify two distinct cellular structures releasing reactive oxygen species immediately at the onset of myonecrosis, i.e. NAD(P)H oxidases that are associated with cellular membranes and enzymes of the mitochondrial membranes. Moreover, we could demonstrate, that labile, redox-active, iron is released in considerable amounts from necrotic myocytes; this might, in combination with the ROS released by damaged cells, pave the way for Fenton-driven oxidative processes to structures in the vicinity of the damaged tissue. As they are generated in great amounts by the destroyed muscle cells, free radicals, iron ions, as well as ATP and different other (oxidised) intracellular substances, moreover might represent decisive mediators of inflammatory reactions subsequent to muscle trauma. In the third period of the project we will continue to unravel the molecular mechanisms of free radical formation upon mechanical trauma to the muscle, assess local consequences of the free radical formation and analyse the systemic liberation of free radicals and related compounds in an animal model and a human study.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Dr. Uta Kerkweg, from 12/2007 until 10/2009