Study of the mechanism of permeabilization of lecithin liposomes and rat liver mitochondria by the antimicrobial drug triclosan

Abstract

The effect of the antimicrobial compound triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol) on the permeability of lecithin liposomes and rat liver mitochondria was studied. It was found that triclosan was able to increase nonspecific permeability of liposomes in a dose-dependent manner, which was detected by the release of the fluorescent probe sulforhodamine B (SRB) from vesicles. A partial release of SRB occurs instantly at the moment of triclosan addition, which is followed by a slow leakage of the dye. The triclosan-induced release of SRB from liposomes grew as pH of the medium was decreased from 9.5 to 7.5. As revealed by the laurdan generalized polarization (GP) technique, triclosan increased laurdan GP in lecithin liposomes, indicating a decrease in membrane fluidity. Measurements of GP as a function of fluorescence excitation wavelength gave an ascending line for triclosan-containing liposomes, which can be interpreted as phase heterogeneity of the lipid/triclosan system. Dynamic light scattering experiments also showed that at a high triclosan-to-lipid molar ratio (~0.5), a population of smaller light-scattering particles (~0.4 of the size of liposomes) appear in the system. Experiments with rat liver mitochondria demonstrated that triclosan (10-70μM) induced a high-amplitude cyclosporin А-insensitive swelling of the organelles accompanied the release of cytochrome c. On the basis of the results obtained, possible mechanisms of the toxic effect of triclosan in eukaryotic cells are discussed.

PPARγ Regulates Triclosan Induced Placental Dysfunction

“…Previous studies indicated that decreased PPARγ expression or the inhibition of PPARγ activity led to mitochondrial fission, hyperpolarization, and increased oxidative stress [ 50 ]. The PPARγ pathway was one mechanism of triclosan-induced mitochondria-targeted effects, regulating the function of these organelles and the permeability of their membranes [ 51 , 52 ]. Our research showed that PPARγ activation or overexpression mitigated, while PPARγ inhibition or silence aggravated the increase of inflammatory gene expression caused by TCS.…”

A Review of Fatty Acid Biosynthesis Enzyme Inhibitors as Promising Antimicrobial Drugs

“…More precisely, triclosan seems to interfere with mitochondrial respiration through both a protonophoric effect and inhibition of complex II activity leading to apoptotic cell death [ 141 ]. More recently, Belosludtsev et al hypothesised that triclosan can also induce mitochondrial toxicity by membranotropic effects (permeabilization of the plasmatic membrane, production of reactive oxygen species, influx of Ca 2+ ) [ 143 ]. Thus, the synthesis of triclosan analogues with less adverse effects motivated medicinal chemists.…”

Triclosan and Its Consequences on the Reproductive, Cardiovascular and Thyroid Levels

“…This inhibition will suppress the membrane phospholipids and the proliferation of microbial cells. TCS has been considered safe for humans and animals since ENR is absent in eukaryotes; however recent studies demonstrate that TCS is considered toxic for eukaryotes [ 30 , 31 ]. It acts primarily on the cytoplasmic membrane and its entry into the cells appears to be by diffusion [ 6 , 23 , 32 , 33 ] due to the lipophilic properties of TCS.…”

“…This mechanism is known as the TCS membranotropic effect. In 2003, Lygre et al demonstrated that this was the mode of action by which TCS exerts its toxic effect on eukaryotes, destabilizing the membrane of a cell or the mitochondria [ 30 , 31 , 34 ].…”