## 1 Introduction  
Chemotherapy and radiation are often accompanied by complications such as intestinal mucositis. This is represented by the disturbance of the intestinal mucosa integrity and is clinically manifested by diarrhea, painful inflammation and ulceration, and in severe cases, hemorrhage, sepsis, ischemia and the formation of strictures [1]. This seems to reflect the high sensitivity of the gastrointestinal tract epithelium to cytotoxic therapies due to the high turnover rate of these cells [2]. Injury to the intestinal epithelium leads to disruption of the integrity of the surface mucosal barrier and allows changes in permeability to various substances and the translocation of bacterial products from the lumen, which contributes to morbidity and mortality. Therefore, gastrointestinal toxicity frequently limits the use of radiation and chemotherapy for the treatment of patients with a wide variety of malignancies [2]. The maintenance of intestinal homeostasis is closely related to the integrity of the epithelial layer renewal. The intestinal epithelial monolayer is composed of different types of specialized epithelial and goblet cells, each with a distinct function. Goblet cells secrete mucous and resistin-like molecule-\(\beta\), which are necessary for the defense and repair of the epithelial layer and in maintaining epithelial homeostasis [3; 4]. This structural and functional integrity allows the permeability of essential ions and water but restricts the entry of pathogens and bacterial toxins [5]. The transport of molecules across the epithelial layer occurs through passive diffusion, the carrier-mediated pathway and the paracellular pathway between the spaces of adjacent cells. The barrier function of the epithelium is provided by the epithelial tight junction proteins, which seals the paracellular space between the apical part of two consecutive epithelial cells and restricts the transport of hydrophilic molecules [6; 7; 8; 9]. The tight junction is composed of several proteins, including occludens; claudins; zonula occludens (ZO); and cingulin, tricellulin and junctional adhesion molecules, which have a complex network between them, as well as with the cytoskeleton. These proteins have specific roles: occludens provide structural integrity to the tight junction [10], claudins are responsible for the regulation of paracellular space [11] and ZO are essential for the connection of other tight junction proteins to the cytoskeleton [12; 13]. Any alteration in the tight junction structure can be detrimental to the structural and functional integrity of the intestinal barrier. Apoptosis plays an important role in determining the architecture of the intestinal epithelium and is also part of the stress response triggered by the toxicant. It appears as a single process, being triggered on several pathways which depend on the position of the cell along the crypt, its level of differentiation and the type of stimulus involved [14]. Under normal conditions, the integrity and normal functioning of the gut is ensured by the apoptosis rate of the gastrointestinal epithelial cells paired with the rate of mitosis [15]. In a previous study, we induced epirubicin-based mucosal barrier injuries of the gastrointestinal tract in mice and found that the small intestine is much more susceptible to damage-induced apoptosis by the intrinsic pathway, followed by the colon and stomach [16], but up to date, there have not been any patho-clinical observations of intestinal changes that follow a standard antineoplastic epirubicin-based protocol applied to once-hematological patients. The aim of this study was to assess by immunohistochemical assay the consequences of epirubicin-based therapy applied to once-hematological patients, on the mucosal cells that undergo apoptosis and on the tight junctions' proteins, immediately before and after a short time of chemotherapy administration.