Oxytetracycline-Protein Complex: The Dark Side of Pet Food

Alessandro Di Cerbo1, 2, *, Antonio Scarano2, Federica Pezzuto3, Gianandrea Guidetti4, Sergio Canello5, Diego Pinetti6, Filippo Genovese6, Lorenzo Corsi1
1 Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
2 Department of Medical, Oral and Biotechnological Sciences, Dental School, University G. d`Annunzio of Chieti-Pescara, Chieti, Italy
3Department of Clinical Science, University of Modena and Reggio Emilia, Modena, Italy
4 SANYpet S.p.a., Research and Development Department, Bagnoli di Sopra (Padua), Italy
5 Forza10 USA Corp., Research and Development Department, Orlando (FL), USA
6 CIGS, University of Modena and Reggio Emilia, Modena, Italy

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© 2018 Di Cerbo et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence this author at the Department of Life Sciences, University of Modena and Reggio Emilia, Alessandro Di Cerbo, Modena, Italy; Tel: 00390592055367; E-mail:



Worldwide antibiotic abuse represents a huge burden, which can have a deep impact on pet and human health through nutrition and medicalization representing another way of antibiotic resistance transmission.


We aimed our research to determine a possible complex formation between biological bone substrates, such as proteins, and Oxytetracycline (OTC), an approved antibiotic for use in zootechny, which might determine a toxic effect on K562 cells.


Cell viability and HPLC-ESI/QqToF assays were used to assess potential toxicity of bone extract derived from OTC-treated chickens according to standard withdrawal times and from untreated chickens at 24, 48 and 72h of incubation.


Cell culture medium with ground bone from chickens reared in the presence of OTC (OTC-CCM) resulted significantly cytotoxic at every incubation time regardless of the bone concentration while cell culture medium with ground bone from chickens reared without OTC (BIO-CCM) resulted significantly cytotoxic only after 72h of incubation. HPLC-ESI/QqToF assay ruled out the possible presence of OTC main derivatives possibly released by bone within culture medium until 1 μg/mL.


The presence of a protein complex with OTC is able to exert a cytotoxic effect once released in the medium after 24-48h of incubation.

Keywords: Antibiotic abuse, Oxytetracycline, Protein complex, Cytotoxic effect, Pro-inflammatory effect, K562 cells.