Abdel Aziz Ghanemi
Kunming Institute of Zoology Chinese Academy of Sciences, China
Posters-Accepted Abstracts: J Drug Metab Toxicol
Cell culture is among the most widely used laboratoryapproaches probably because of the diverse aspects it coversand the relatively short period of time it requires. In pharmacologyand therapeutic researches, cell culture represents a largelyused basic approach. The aim of the modern pharmacology isto first identifies active compounds from natural elements that can constitute a starting point to develop therapeutic drugs. Nowadays, the drug development lies mainly on the identification of compounds that are thought to be active based on their chemical structures are based on observation reported by biologists or physiologists for example. Those compounds are then further investigated. The first step in drug discovery is, in many cases, to test compounds in cell culture to find out how active they are in terms of pharmacological actions. The challenges faced in this step are diverse. Indeed, selecting the cell line is an important issue since the compound activity may be specific. Defining the optimum conditions for both the cell culture media and the drug, solvent, in addition to the other reagents that are eventually used, remains important since a variation of each of these factors could affect the robustness of the cell-based assay by influencing the live cells and therefore the assay├ó┬?┬?s results. Another important element is the choice of the positive control, which is in many cases a commonly used drug that is well studied and well known for the activity we are about to test. Importantly, the use of negative controls assures a better interpretation of the results since it allows us to distinguish the effects of the tested drugs from those due to other elements such as the reagents or the cell culture medium ingredients. For instance, many pharmacological discoveries related toone of the most important pharmacological targets, G protein coupled receptors have been made, thanks to cell cultures and the related bio-molecular methods.We expect more advances due to the high diversity of the existent cell strains and the similarities that exist between the pathways within those cells and some human disease mechanisms we want to elucidate in order to treat the underlying causes instead of just managing the symptoms. Yet, an active compound does necessary mean a future drug since toxicological studies chemical investigation, clinical trials and legal issues may exclude a compound from further development processes towards a recognized drug. However, cell culture-based assays cannot provide the full pharmacological profile since the data they provided are limited to some molecular and cellular aspects such as pharmacodynamic, biochemical pathways and genetic variations. Since cell-culture studies focus on isolated cells apart from tissues or organisms, the influence of some elements that can interfere with the pharmacological receptors, for example, including some chemical environments, hormones and fluid pressure cannot be studied. Importantly, some pharmacokinetic parameters cannot be studied by cell cultures, and animal experiments remain required to achieve this purpose. Focusing on the challenges facing the application of cell culture techniques in drug discovery and overcoming them would further exploit this important method for drug discovery and drug development research.