**1. Introduction**

Foodstuffs and feed contamination, including simultaneous contamination of agricultural products with numerous mycotoxins and modified mycotoxins, is a frequent and widely recognised worldwide problem [1–4]. These unavoidable toxins are secondary metabolites produced by different genera of filamentous fungi. They occur on dietary staple foods and fodder, especially cereals, along the whole production chain, including under pre- and post-harvest conditions. In Europe, the most frequently reported mycotoxins and secondary metabolites in feed include deoxynivalenol (DON), zearalenone, ochratoxin A, fumonisin B1, fumonisin B2, and T2/HT2 toxin [3]. Considering pigs' diet, cereals, including maize and cereal-based products, are probably the most commonly used constituents in feed, supplying most of the animal's nutrients. Nevertheless, there are mycotoxins in maize called trichothecenes, most importantly zearalenone and DON [2,3,5,6].

Deoxynivalenol is a type B trichothecene produced by Fusarium species. It is believed to be one of the least acutely toxic trichothecenes, but it is highly incident and relevant in

**Citation:** Mendel, M.; Karlik, W.; Latek, U.; Chłopecka, M.; Nowacka-Kozak, E.; Pietruszka, K.; Jedziniak, P. Does Deoxynivalenol Affect Amoxicillin and Doxycycline Absorption in the Gastrointestinal Tract? Ex Vivo Study on Swine Jejunum Mucosa Explants. *Toxins* **2022**, *14*, 743. https://doi.org/ 10.3390/toxins14110743

Received: 11 October 2022 Accepted: 26 October 2022 Published: 29 October 2022

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animal husbandry [4]. Chronic exposure to low doses of this mycotoxin heavily suppresses the immune response and intestinal functions, induces anorexia, reduces weight gain, and causes neuroendocrine changes [7–10]. There is sufficient evidence revealing the impairing effect of DON on gut barrier permeability and integrity. The mycotoxin induces the activity of mitogen-activated protein kinases (MAPKs) and decreases the expression of tight junction proteins [11].

Consequently, bacteria and antigens translocation from the lumen of the gut might be intensified [11,12]. Despite the knowledge of DON's potency to change intestine permeability, little interest has been paid so far to its possible effects on the absorption rate of other xenobiotics at the time of combined exposure [13–16]. In addition to nutrients, the spectrum of chemicals which might be found in the lumen of the gut due to conscious administration of feed and environmental contaminations include veterinary medicinal products (VMPs), feed additives, fertilisers, plant protection products, air pollutants, and others.

In the case of VMPs, a group of special considerations are antimicrobials. Their use in modern pig production remains one of the elements in maintaining animal health. However, under some conditions, the hazards related to their use could negate their benefits due to the potential risks, including exposure to antimicrobial residues in food or the environment [17,18]. Using antimicrobials might provoke antimicrobial resistance in animal- and human-related bacteria, and thus, compromise animal and human health [19].

Amoxycillin (AMX) and doxycycline (DOX) represent two commonly used antimicrobials for oral application in pigs. Their recommended doses guarantee effectiveness against pathogens and safety of use. Dosing antibiotics (as with all drugs) is based on pharmacokinetic parameters, of which oral bioavailability is one of the key parameters. In the case of orally administered antibiotics in food-producing animals, the level of absorption of the medicine from the gastrointestinal tract affects not only its antibacterial efficacy but also is essential for the safety of food consumers and the environment. In the event of a disturbance in the functioning of the intestinal barrier, the bioavailability of an orally administered antibiotic may change, which in turn may affect the effectiveness and safety of its action. To the best of our knowledge, there is hardly any evidence of the interaction of mycotoxins with antimicrobials within the gastrointestinal tract. An in-depth literature search revealed only one study by Goossens et al. [13] on DON–DOX interaction at the stage of absorption in pigs. Therefore, this study aimed to verify the impact of DON on two antibiotics' (AMX and DOX) absorption in the intestine isolated from clinically healthy pigs.

#### **2. Results**
