title: Detrimental effects of chemotherapeutics and other drugs on the endothelium: A call for endothelial toxicity profiling.
abstract: The vascular endothelium is a real "maestro of circulation", and endothelial dysfunction leads to atherothrombosis, its cardiovascular complications, as well as to many other diseases. It is surprising that quite a large number of drugs seem to hamper the vasoprotective mechanisms of the endothelium, possibly promoting the development of cardiovascular diseases in patients initially treated for non-cardiological conditions. Toxicity profiling (including cardiac and liver toxicity assessment) is a routine procedure performed during pre-clinical drug development. Unfortunately, endothelium-dependent side effects are not taken into account in standard toxicity profiling protocols, as the "endothelial safety" of drugs is not required in order to enter the clinical phase of drug development. Presumably, this might be one of the reasons why several efficient therapeutics, including rofecoxib (COX-2 inhibitor), torcetrapib (CETP-inhibitor), and bardoxolone (Nrf2 activator), have unexpectedly displayed clinically significant cardiovascular hazard, resulting in their withdrawal from the market or alarming comments, respectively. In this review, we will briefly characterize the endothelial activity profiles of chemotherapeutics, antidepressants and antipsychotics-all drugs prescribed for severe, life-threatening and/or life-long diseases-and will show that at least some of them may display clinically relevant detrimental effects on endothelial function.
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland.
authors: Tomasz
authors: T
authors: Wojcik
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland.
authors: Ewa
authors: E
authors: Szczesny
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland; Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: stefan.chlopicki@jcet.eu.
authors: Stefan
authors: S
authors: Chlopicki
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans
chemical_list: D000928:Antidepressive Agents; D000970:Antineoplastic Agents; D014150:Antipsychotic Agents; D052246:Cyclooxygenase 2 Inhibitors
keywords: Antidepressants; Antipsychotic agents; Chemotherapeutics; Endotheliotoxicity; Endothelium