Rapid method for comparing the cytotoxicity of organic solvents and their ability to destabilize proteins of the erythrocyte membrane.
Cytotoxicities of a group of frequently used organic solvents were assessed by their effect on thermal stability of erythrocyte membrane proteins. The denaturation temperatures Tm of membrane proteins, peripheral and intrinsic, were detected by the increase in the derivative of suspension impedance during heating. These Tm linearly changed by delta Tm in the presence of organic solvents indicating labilization (negative delta Tm) or stabilization (positive delta Tm) of the structure of respective membrane protein. The potency P of the solvent with molar concentration Cex to affect the conformation stability of membrane protein was defined as delta Tm/Cex. This potency decreased as both polarity of solvent and its capability to form hydrogen bonds increased. In some solvents (dimethyl sulfoxide and dimethyl formamide) the potencies to destabilized peripheric and intrinsic proteins were equal. Formamide destabilized selectively peripheral proteins. Some solvents (glycerol, especially erythritol) stabilised thermally proteins. As the hydrophobicity of the solvents increased (ethylene glycol, methanol, ethanol, acetone, pyridine, ethyl acetate, diethyl maleate) the potency for destabilization of intrinsic proteins strongly increased. Thus, the use of more polar solvents capable of forming more hydrogen bonds appears preferable when low cytotoxicity should be attained.
Ivanov
I T
IT
Department of Physics & Biophysics, Medical Institute of Thracian University, Stara Zagora, Bulgaria. ivanov_it@hotmail.com
D001798:Blood Proteins / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects*; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D011487:Protein Conformation; D012997:Solvents / Q000633:toxicity*; D013696:Temperature; D013816:Thermodynamics
D001798:Blood Proteins; D012997:Solvents