title: Toxicity assessment of hydroxyapatite nanoparticles in rat liver cell model in vitro.
abstract: Hydroxyapatite nanoparticles (HAP NPs) are widely used for preparations of biomedical and biotechnological fields such as drug delivery, gene therapy, and molecular imaging. However, the current toxicological knowledge about HAP NPs is relatively limited. The present study was designed to investigate the toxicity potentials of various concentrations (0-1000 µg cm(-2)) of HAP NPs in cultured primary rat hepatocytes. Cell viability was detected by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed via scoring liver micronuclei rates and determining 8-oxo-2-deoxyguanosine (8-OH-dG) levels. The results of MTT and LDH assays showed that the higher concentrations of dispersed HAP NPs (300, 500, and 1000 µg cm(-2)) decreased cell viability. Also, HAP NPs increased TOS (500 and 1000 µg cm(-2)) levels and decreased TAC (300, 500, and 1000 µg cm(-2)) levels in cultured hepatocytes. On the basis of increasing doses, the NPs as depending on dose caused significant increases of the number of micronucleated hepatocytes and 8-OH-dG levels as compared to control culture. Furthermore, the highest concentration of HAP NPs (1000 µg cm(-2)) exhibited cytotoxic activity. Based on these results, HAP NPs have a dose-dependent toxic effect in rat hepatocytes. Further extensive research in this field is promising and reasonable.
authors.affiliation: Department of Physics, Faculty of K. K. Education, Atatürk University, Erzurum, Turkey Advanced Materials Research Laboratory, Department of Nanoscience and Nanoengineering, Graduate School of Natural and Applied Sciences, Atatürk University, Erzurum, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Sonmez
authors.affiliation: Department of Pharmacology, G. D'Annunzio University, Chieti, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Cacciatore
authors.affiliation: SUNUM, Sabanci University, Tuzla, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Bakan
authors.affiliation: Department of Pharmacology, G. D'Annunzio University, Chieti, Italy Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Turkez
authors.affiliation: Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.
authors.forename: Y I
authors.initials: YI
authors.lastname: Mohtar
authors.affiliation: Department of Biology, Faculty of Science, Atatürk University, Erzurum, Turkey basaktogar@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Togar
authors.affiliation: Department of Pharmacology, G. D'Annunzio University, Chieti, Italy.
authors.forename: A D
authors.initials: AD
authors.lastname: Stefano
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017886:Durapatite / Q000737:chemistry / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D017886:Durapatite; D003849:Deoxyguanosine
keywords: Hydroxyapatite nanoparticles; cytotoxicity; genotoxicity; oxidative stress; rat hepatocytes