title: Cytotoxic effects of oxytetracycline residues in the bones of broiler chickens following therapeutic oral administration of a water formulation.
abstract: Tetracyclines, which represent one of the most commonly used antibiotics for poultry, are known to be deposited in bones, where they can remain, despite the observation of appropriate withdrawal times. The aim of the study was to determine the concentration of oxytretracycline (OTC) residues in the bone and muscle of chickens, following the oral administration of a commercially available liquid formulation, and to test their cytotoxic effects on an in vitro cell culture model. Seventy-two 1-day-old broiler chickens were randomly allotted into 2 groups (control and treated animals). OTC (40 mg/kg BW) was administered via drinking water during the 1 to 5 and 20 to 25 days of life periods. At the end of the trial, the birds were slaughtered and the OTC residues in the target tissues were measured by means of liquid chromatography (LC) - tandem mass spectrometry (MS/MS). Cytotoxicity was assessed by evaluating the pro-apoptotic effect of the bone residues on the K562 erythroleukemic line and on the peripheral blood mononuclear cells (PBMC). In all the animals, the OTC residues in the muscle were far below the established MRL of 100 μg/kg. The OTC levels in the bones of the treated animals were instead found in the parts per million (ppm) range. Cell cytotoxicity was assessed by evaluating the pro-apoptotic effect of OTC bone residues on the haematopoietic cell system. This in vitro system has revealed a significant pro-apoptotic effect on both the K562 cell line and PBMC cultures. This result suggests potential human and animal health risks due to the entry of tetracycline residues contained in the bones of treated livestock into the food-chain. This could be of concern, particularly for canine and feline diets, as meat, bone meal, and poultry by-products represent some of the main ingredients of pet foods, especially in the case of dry pet food. Further studies are needed to define the underlying mechanisms of cytotoxicity and to evaluate the in vivo toxicological implications due to the observed in vitro effects.
authors.affiliation: Department of Veterinary Science, University of Turin, 10095 Grugliasco (TO), Italy.
authors.forename: R
authors.initials: R
authors.lastname: Odore
authors.affiliation: Department of Veterinary Science, University of Turin, 10095 Grugliasco (TO), Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Marco
authors.affiliation: Department of Agricultural, Forest and Food Sciences, University of Turin, 10095 Grugliasco (TO), Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gasco
authors.affiliation: Department of Agricultural, Forest and Food Sciences, University of Turin, 10095 Grugliasco (TO), Italy.
authors.forename: L
authors.initials: L
authors.lastname: Rotolo
authors.affiliation: Department of Veterinary Science, University of Pisa, 56126 Pisa, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Meucci
authors.affiliation: Department of Science, University of Basilicata, 85100 Potenza, Italy Ph.D School of Science, University of Basilicata, 85100 Potenza, Italy.
authors.forename: A T
authors.initials: AT
authors.lastname: Palatucci
authors.affiliation: Department of Traslational Medical Science, University of Naples Federico II, 80131 Napoli, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Rubino
authors.affiliation: Department of Traslational Medical Science, University of Naples Federico II, 80131 Napoli, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ruggiero
authors.affiliation: Department of Research and Development, Sanypet Spa, 35023 Bagnoli di Sopra (PD), Italy.
authors.forename: S
authors.initials: S
authors.lastname: Canello
authors.affiliation: Department of Research and Development, Sanypet Spa, 35023 Bagnoli di Sopra (PD), Italy.
authors.forename: G
authors.initials: G
authors.lastname: Guidetti
authors.affiliation: Department of Research and Development, Sanypet Spa, 35023 Bagnoli di Sopra (PD), Italy.
authors.forename: S
authors.initials: S
authors.lastname: Centenaro
authors.affiliation: Department of Food Science, University of Parma, 43124 Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Quarantelli
authors.affiliation: Department of Science, University of Basilicata, 85100 Potenza, Italy Department of Traslational Medical Science, University of Naples Federico II, 80131 Napoli, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Terrazzano
authors.affiliation: Department of Veterinary Science, University of Turin, 10095 Grugliasco (TO), Italy achille.schiavone@unito.it.
authors.forename: A
authors.initials: A
authors.lastname: Schiavone
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000633:toxicity; D001842:Bone and Bones / Q000737:chemistry*; D002460:Cell Line; D002645:Chickens / Q000378:metabolism*; D060766:Drinking Water; D004350:Drug Residues / Q000737:chemistry*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D010118:Oxytetracycline / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D060766:Drinking Water; D010118:Oxytetracycline
keywords: bone residue; broiler chicken; cytotoxicity; oxytetracycline