Role for Membrane Fluidity in Ethanol-Induced Oxidative Stress of Primary Rat Hepatocytes

Abstract

The relationship between bulk membrane fluidizing effect of ethanol and its toxicity due to oxidative stress is still unknown. To elucidate this issue, membrane fluidity of primary rat hepatocytes was studied by measuring order parameter after inhibition of ethanol-induced oxidative stress. We showed that pretreating cells with either 4-methyl-pyrazole (to inhibit ethanol metabolism), thiourea [a reactive oxygen species (ROS) scavenger], or vitamin E (a free radical chain-breaking antioxidant) prevented the ethanol-induced increase in membrane fluidity, thus suggesting that ethanol metabolism and ROS formation were involved in this elevation. The effects of membrane stabilizing agents (ursodeoxycholic acid or ganglioside GM1), shown to prevent fluidification, next pointed to a role for this increase in membrane fluidity in the development of ethanolinduced oxidative stress. Indeed, ROS production, lipid peroxidation, and cell death were all inhibited by these agents. In contrast, the fluidizing compounds Tween 20 or 2-(2-methoxyethoxy) ethyl 8-(cis-2-n-octylcyclopropyl) octanoate, which increased the membrane fluidizing effect of ethanol, enhanced the related oxidative stress. Using electron paramagnetic resonance to determine low molecular weight iron, we finally demonstrated that membrane fluidity influence proceeded through an increase in low molecular weight iron to enhance oxidative stress. In conclusion, the present findings clearly highlight the pivotal role of membrane fluidity in ethanolinduced oxidative stress and the potential therapeutic effect of membrane stabilizing compounds.

Modification of Plasma Membrane Organization in Tobacco Cells Elicited by Cryptogein

“…Similarly, temperature-and benzyl alcohol-induced fluidification were shown to be associated with an increase in large, cholesterol-rich domains in melanoma cells (Nagy et al, 2007). Ethanol-induced oxidative stress is dependent on the clustering of lipid ordered domains in primary rat hepatocytes (Nourissat et al, 2008) and is associated with membrane fluidity increase (Sergent et al, 2005). The transient fluidification of the tobacco cell PM specifically induced by cryptogein (Fig.…”

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

“…35 Their mode of action varies in different cell types, including altering the activity of several enzymes and specific proteins, [36][37][38][39][40] membrane stabilisation and fluidity, 34,35 scavenging hydroxyl radicals. 41 Even if there were a consensus on the protective effects of gangliosides against cellular damage, the mechanism(s) underlying these effects and the models in which gangliosides are protective would still require precise evaluation.…”

“…35 In vivo, GT1b prevents chemically induced DNA damage in mice. 41 There is evidence that the antioxidative properties of GM1 are dependent on its effect on iron ion exchange 35,42 because iron ions are involved in ROS and LPO product formation in many cell types.…”

Quercetin and epigallocatechin gallate effects on the cell membranes biophysical properties correlate with their antioxidant potential

“…There are several research reports that link the microviscosity of cell membranes to the effects induced by different toxic stimuli. The increase of hepatocytes membrane fluidity under the influence of some xenobiotics (such as tacrine, ximelagatran or ethanol) is related to drug-induced liver injury and is leading to substantial disturbances of cell function (Sergent et al 2005(Sergent et al , 2009). Fujimoto et al (1999) proved that cells exposed to apoptotic stimuli exhibit alterations of membrane fluidity.…”