Toxicity Screening of Therapeutic Drugs

INTRODUCTION In the course of in vitro systems search for the toxicity screening of therapeutic drugs (TDs), different cellular models have been applied to examine their adverse effects in isolated organs. This article describes a simple method to determine effects of TDs at the cell membrane level. The cell membrane is an assembly of proteins and lipids that separate inside from outside, protecting the cell interior. The membrane is also involved in a variety of indispensable cellular functions. It is responsible for the selective transport of molecules and ions into and out of the cell in the extensive network responsible for the traffic between organelles. Without exception, these activities depend on, and are influenced by the physical milieu provided by the molecules making up the membrane bilayers. Changes in the physical and chemical environment of the cell membranes have a direct effect on the membrane structure with serious effects on the cell functions [1–2]. Most biological membranes possess an asymmetric trans-bilayer distribution of phospholipids [3]. Thus, for instance, most eukaryotic plasma membranes present a high percentage of the phospholipids sphingomyelins and phosphatidylcholines in the outer monolayer, whereas the inner one is generally richer in phosphatidylethanolamines, phosphatidylserines, and phosphatidylinositols. However, the existence of asymmetric plasma membranes is less certain in bacteria than in eukaryotes. Studies of the phospholipid distribution of a grampositive bacteria revealed that the outer monolayer is rich in phosphatidylglycerols, the inner one in phosphatidylinositols, while cardiolipins are symmetrically distributed between both monolayers. Studies on gram-negative bacteria such as Escherichia coli have detected phosphatidylethanolamines in the outer membrane, whereas the cytoplasmic membrane has been reported to be rich in phosphatidylglycerols and cardiolipins.