Detergent cell toxicity

Compounds that show general eukaryotic cell toxicity may give rise to false positives, or show nonspecific activity, in cell-based assays. (Some of these also act by damaging membranes and may overlap with the detergent-like class of compounds.)... 

MTT assay is a standard colorimetric assay used to determine cytotoxicity of potential medicinal agents and other toxic materials. It is based on the reduction of the tetrazolium salt MTT by viable cells. A mitochondrial dehydrogenase enzyme is able to cleave the tetrazolium rings of the pale yellow MTT and form dark purple formazan crystals, which are largely impermeable to cell membranes resulting in the accumulation of these crystals within healthy cells. Solubilization of the cells by the addition of a detergent results in the liberation of crystals, which are solubilized. The metabolic activity of cells is directly proportional to the concentration of the created formazan product (22), whose color is quantified in a colorimetric assay. 

Plants are not different from other natural product samples in that they too tend to interfere with various screening formats in nonspecific ways as nuisance compounds displaying unwanted color, inherent fluorescence, promiscuous or aggregate behaviors, detergent-like activities, or toxicity (Feng et al., 2005 Appleton, Buss, and Butler, 2007). Biochemical assays (cell-free defined systems) are notoriously sensitive to such interference by natural product extracts. Cell-based reporter assays and cell-based so-called phenotypic screens always require parental cell controls to determine extract toxicity. However, plants contain their own sets of components that are problematic to screening assays and compound identification. 

Figure 1.8 Schematic view of the ecological roles of plant SM. Foxglove (Digitalis purpurea) produces cardiac glycosides, which are very toxic to animals (vertebrates, insects) because they inhibit Na+, K -ATPase, one of the most important transporters in animal cells. Cardiac glycosides are additionally toxic to microbes because the molecules have detergent properties and disturb membrane fluidity. (See Plate 7 in colour plate section.)...

Functioning as detergents, hydrophobic (Hpophiiic) bile acids (cholic add, chenodeoxycholic add, deoxychohc add, hthochohc acid) exert toxic efifects on the biomembranes of liver cells and mitochondria. At the same time, these bile acids display an immunosuppressive elfect and influence the humoral and cell-mediated defence (e.g. inhibition of monocytes). As in the case of PBC, hydrophobic bile acids also induce an excessive expression of MHC-I and MHC-II molecules from hepatocytes and bihary cells. 

Human safety evaluations begin with the specific ingredients, and then move on to the whole product. The effects for all ingredients are considered as the product is formulated. Human safety-related data for a chemical used in a detergent or soap product (or in another type of consumer product), and for an entire formulation, can come from in silico data (from computer programs that estimate toxic properties based on data for similar chemicals, and/or from the physical chemical properties of the chemical of interest), in vitro data (from the results of alternatives to animal tests, e.g., from cell cultures used to assess eye or skin irritation potential), animal (toxicological) studies (e.g., to assess eye or skin irritation potential), and human data (examples are discussed below). 

Attempts are being made to find agents that will rupture the membranes of cancer cells selectively. For example amines, stich as 4-dodecylpyridine 14.20), with a pX a value between 5 and 9, are selectively accumulated by lysosomes because these have an acidic sap, as have cancer cells (p. 151). The amines enter the cells freely, being non-ionized and lipophilic, but are trapped as cations by the acidic sap and cannot escape. Because the cations (but not the neutral species) are detergents, the lysosomal membranes become ruptured, and it is hoped to adapt this phenomenon to anti-cancer therapy. 4-Dodecylpyridine is non-toxic to mice after intraperitoneal injection of 0.5 g/kg (Firestone, Pisano and Bonney, 1979). 

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