Idiosyncratic Organotoxicity - Research Groups
Prof. Stephan Krähenbühl, MD, PhD |  |
Idiosyncratic organotoxicity (Stephan Krähenbühl, main applicant)
During the last 10 years, the focus of this group has been on the mechanisms and risk factors of idiosyncratic toxins, in particular toxins affecting the liver and/or skeletal muscle. Regarding mechanisms, a special field of interest was mitochondrial toxicity. We have described the effect of amiodarone and amiodarone derivatives on liver mitochondria and cultured hepatocytes (1). We have for instance explored the mechanism of hepatic toxicity of benzbromarone, which can cause a Reye syndrome-like type of hepatotoxicity in specific patients. Regarding amiodarone, we explored the possibility to separate mitochondrial toxicity from its pharmacological action (2). We have also described the toxicity of statins on isolated rat skeletal muscle mitochondria and on cultured myocytes (3). Statins are mitochondrial toxins, a finding possibly relevant for rhabdomyolysis associated with these drugs. Valproate is another drug we have investigated in detail. Based on clinical observations and laboratory investigations, we hypothesized that mitochondrial diseases are risk factors for hepatic toxicity of valproate (4). Most recently, we have described hepatotoxicity of valproate in an animal model with carnitine deficiency, supporting our hypothesis (5).
Last Updated on Thursday, 25 March 2010 15:37 Created: Tuesday, 07 April 2009 13:27
