title: Biphasic Response to Luteolin in MG-63 Osteoblast-Like Cells under High Glucose-Induced Oxidative Stress.
abstract: BACKGROUND
  Clinical evidence indicates the diabetes-induced impairment of osteogenesis caused by a decrease in osteoblast activity. Flavonoids can increase the differentiation and mineralization of osteoblasts in a high-glucose state. However, some flavonoids such as luteolin may have the potential to induce cytotoxicity in osteoblast-like cells. This study was performed to investigate whether a cytoprotective concentration range of luteolin could be separated from a cytotoxic concentration range in human MG-63 osteoblast-like cells in high-glucose condition.
  
  
  METHODS
  Cells were cultured in a normal- or high-glucose medium. Cell viability was determined with the MTT assay. The formation of intracellular reactive oxygen species (ROS) was measured using probe 2',7' -dichlorofluorescein diacetate, and osteogenic differentiation was evaluated with an alkaline phosphatase bioassay.
  
  
  RESULTS
  ROS generation, reduction in alkaline phosphatase activity, and cell death induced by high glucose were inhibited by lower concentrations of luteolin (EC50, 1.29±0.23 µM). Oxidative stress mediated by high glucose was also overcome by N-acetyl-L-cysteine. At high concentrations, luteolin caused osteoblast cell death in normal- and high-glucose states (IC50, 34±2.33 and 27±2.42 µM, respectively), as represented by increased ROS and decreased alkaline phosphatase activity.
  
  
  CONCLUSIONS
  Our results indicated that the cytoprotective action of luteolin in glucotoxic condition was manifested in much lower concentrations, by a factor of approximately 26 and 20, than was its cytotoxic activity, which occurred under normal or glucotoxic condition, respectively.
authors.affiliation: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Abbasi
authors.affiliation: Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran.
authors.forename: Afra
authors.initials: A
authors.lastname: Khosravi
authors.affiliation: Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Aidy
authors.affiliation: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Massoumeh
authors.initials: M
authors.lastname: Shafiei
keywords: Alkaline phosphatase; High glucose; Human osteoblast-like MG-63 cells; Luteolin; Oxidative stress