Antibiotic residues: A step forward towards the understanding of their toxic role in food and feed

Introduction: The worldwide use of antibiotics, particularly for intensive farming, is a well-recognized concern. These drugs prevent or treat overcrowding pathologies and improve animal growth and productivity. Nevertheless, their residues in food and feed pose serious health risks among consumers and pets. In particular, we investigated the toxic potential of oxytetracycline (OTC), alone or within the animals' bones, both in vitro and in vivo. Materials and Methods: To determine the toxic potential of OTC, CCK-8 cytotoxicity assay, flow cytometry chromatin immuno-precipitation, western blot analysis, and Micropipette Aspiration Technique (MAT) were carried out on human peripheral blood mononuclear cells (PBMCs) and K562 cells. At the same time, ELISA assays for detecting OTC in the sera of pets and humans were also performed. Results: CCK-8 assay and flow cytometry revealed a significant pro-apoptotic and pro-inflammatory [interferon (IFN)-γ] effect of OTC in K562 and PBMCs, respectively. Further, PBMCs showed DNA damage features, including ATM and p53 activation, while MAT carried out in K562 revealed time-dependent apoptosis within 12-h exposure to the antibiotic. Besides such observations, we unexpectedly found high levels of OTC in the sera of humans and pets. Conclusions: Our results, although preliminary, pose a new concern about the toxic potential of OTC, in particular once bound to the animals' bones. Moreover, such toxicity opens a debate about including the bone as a matrix to be considered in the national regulations about Maximal Residual Limits. We hypothesize that the unexpected presence of OTC within animal and human sera could be the direct consequence of prolonged food and feed intake and might represent a new research focus to explain the antibiotic resistance phenomenon.