**1. Introduction**

Alcoholism is a severe health problem worldwide. Even if it is not itself the direct cause of death, ethanol abuse is associated with many health risks, including poisoning and the greater spread of HIV and tuberculosis. Alcohol negatively affects various types of blood cells and their functions. Ethyl alcohol abusers most often have defective red blood cells; they are destroyed prematurely, leading to anemia. Drinking too much ethyl alcohol can increase stroke risk as it affects the blood coagulation system [1]. Ethyl alcohol is toxic to the bone marrow (it contains blood cell precursors) and all cells circulating in the blood [2]. Microscopic examination of cultured blood cell precursors has shown that exposure of cells to a wide range of ethyl alcohol concentrations causes damage to the membrane surrounding each cell.

Alcoholism can also modify blood clotting or coagulation. Alcohol consumption can interfere with these processes at several levels, causing thrombocytopenia (abnormally low blood platelet count), thrombocytopathy (impaired platelet function), and reduced fibrinolysis. Researchers have suggested that alcohol intoxication itself causes a decrease in blood platelets. Literature data also indicate that alcohol shortens existing thrombocytes' lifespan and may affect the late stage of platelet production. Alcohol abuse also affects the properties of thrombocytes. These platelet abnormalities include impaired platelet aggregation and decreased secretion or activity of platelet-derived proteins involved in blood coagulation [3–7].

Even small changes in the composition of cell membranes can strongly affect their functioning and physicochemical properties. These changes may occur due to the modi-

**Citation:** Petelska, A.D.; Szeremeta, M.; Koty ´nska, J.; Niemcunowicz-Janica, A. Experimental and Theoretical Approaches to Describing Interactions in Natural Cell Membranes Occurring as a Result of Fatal Alcohol Poisoning. *Membranes* **2021**, *11*, 189. https://doi.org/ 10.3390/membranes11030189

Academic Editor: Francisco Monroy

Received: 28 January 2021 Accepted: 5 March 2021 Published: 9 March 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

fication of cell membranes by short-chain alcohols like ethanol, a particularly important representative of molecules that can modulate membranes' properties. As a first approximation to understanding the interaction of ethanol with cell membranes, lipid bilayers are considered. This interaction is of biophysical interest as ethyl alcohol can induce the formation of interdigitated bilayer structures and modulate lipids' phase stability. Numerous experimental and computational studies have been performed to determine how ethyl alcohol affects lipid bilayers [8–10]. Although the alcohol has an amphiphilic nature, its hydrophobicity is limited; it can pass through the bilayer. Besides this, ethanol molecules condense near the interface region between lipids and water. –OH groups are positioned in the bilayer interfacial region (forming hydrogen bonds with hydrophilic lipid headgroups), and the hydrocarbon chains face the hydrophobic core of the bilayer. The presence of ethanol in the lipid membrane has a disordering effect on the hydrocarbon chains, giving rise to an increase in the membrane's area per lipid and fluidity.

The interaction of ethyl alcohol with lipid membranes, both natural and model, has been examined for years. Alcohol-induced modifications in erythrocyte membranes have been extensively investigated using different experimental methods such as Electron paramagnetic resonance spectroscopy (EPR) spectroscopy [11,12], fluorescence anisotropy [13,14], gas chromatography [15], and microelectrophoresis [16–18]. Nevertheless, there is limited data concerning the influence of ethanol poisoning on thrombocyte membranes. In the literature, one can find microelectrohoretic studies of cell membranes' electric properties when intoxicated with ethanol, but it should be emphasized that these reports concern rats. The authors found that alcohol significantly enhanced changes in the surface charge density of erythrocyte membranes [17] and liver cell membranes [18]. The obtained results indicate that changes in cell membrane charge connect with changes in membrane composition.

In recent years, studies of the electrical properties of cell membranes have focused mainly on model membranes—monolayers [19], bilayers [20], and supported lipid membranes [21]—while there are few papers concerning natural membranes [22,23]. The results included in this paper are a continuation of the systematic research on the electrical properties of blood cell membranes conducted by Petelska et al. [24–28]. In this work, we analyze the influence of fatal ethanol poisoning on human blood cell membranes' surface charge, which is an important parameter describing equilibria in both model and natural membranes.

Erythrocytes and thrombocytes have relatively simple structures. Thus, they are ideal cellular models to study the alterations of membranes' physicochemical properties under the influence of small amphiphilic solutes, like ethanol. In cellular systems, the toxicity of ethyl alcohol has been suggested to be due to its interactions with membranes [29]. Due to the lack of literature data on the effect of fatal poisoning with ethyl alcohol on the equilibria between the membranes of erythrocytes and thrombocytes and the surrounding environment, we proposed a mathematical model to describe these equilibria. The obtained data indicate the influence of alcohol intoxication on the blood cell membranes. In our opinion, our quantitative description of the properties of erythrocyte and thrombocyte membranes may help to better understand the impact of fatal ethyl alcohol poisoning on the surface properties of blood cell membranes.
