title: [Decrease in toxicity and therapeutic effect of zoledronic acid in combination therapy with different antioxidant extracts].
abstract: BACKGROUND
  Zoledronic acid is used in the treatment of cancer-related diseases, although its use has been associated with avascular osteonecrosis.
  
  
  OBJECTIVE
  To determine the possible protective effect of a range of antioxidant substances against the inhibition of human prostate epithelial cell growth (PNT2) and transgenic adenocarcinoma mouse prostate tumour cells (TRAMP-C1), in treatments combining zoledronic acid and ionising radiation (IR).
  
  
  METHODS
  Cell survival is studied via cell viability assays (MTT) for 2 cell lines in isolated and combined treatments with zoledronic acid and/or IR, as well as the effect of adding 3 antioxidant substances.
  
  
  RESULTS
  Zoledronic acid displays a significant cytotoxic effect over PNT2 and TRAMP-C1 cells (P<.001). The administration of antioxidants together with the zoledronic acid shows a protective effect for normal prostate cells, yet not so for prostate tumour cells. However, the administration of rosmarinic acid and apigenin in treatments combined with zoledronic acid provides a protective effect from the harmful effects of applying ionizing radiation, not only for normal PNT2 cells, but also for tumour cells.
  
  
  CONCLUSIONS
  The use of antioxidant substances decreases the cytotoxic effect of zoledronic acid over non-tumour cells, and as such could be used in benign diseases. Furthermore, in the combined treatment using ionising radiation, these antioxidants also produced a protective effect in tumour cells, thus reducing the therapeutic effect sought by combining the treatment with radiation.
authors.affiliation: Departamento de Radiología, Facultad de Medicina/Odontología, Universidad de Murcia, Campus Espinardo, Murcia, España; Departamento de Medicina Física, Facultad de Medicina/Odontología, Universidad de Murcia, Campus Espinardo, Murcia, España.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Lopez-Morata
authors.affiliation: Departamento de Radiología, Facultad de Medicina/Odontología, Universidad de Murcia, Campus Espinardo, Murcia, España; Departamento de Medicina Física, Facultad de Medicina/Odontología, Universidad de Murcia, Campus Espinardo, Murcia, España.
authors.forename: Amparo
authors.initials: A
authors.lastname: Olivares
authors.affiliation: Departamento de Radiología, Facultad de Medicina/Odontología, Universidad de Murcia, Campus Espinardo, Murcia, España; Departamento de Medicina Física, Facultad de Medicina/Odontología, Universidad de Murcia, Campus Espinardo, Murcia, España. Electronic address: mab@um.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcaraz
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000633:toxicity*; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms; D000077211:Zoledronic Acid
chemical_list: D000975:Antioxidants; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Efectos de la radiación; Effects of radiation; Radio-protective; Radio-sensitising; Radioprotectores; Radiosensibilizantes; Zoledronic acid; Ácido zoledrónico