Biphasic response to luteolin in MG-63 osteoblast-like cells under high glucose-induced oxidative stress

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 [EC[50], 1.29 +/- 0.23 micro M]. 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 [IC[50], 34 +/- 2.33 and 27 +/- 2.42 micro M, respectively], as represented by increased ROS and decreased alkaline phosphatase activity

Conclusion: 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

Noscapine antagonizes vasoconstrictor action of bradykinin in isolated human umbilical artery

It has been demonstrated that noscapine, an antitussive opioid alkaloid, could antagonize bradykinin-induced responses such as bradykinin effects in guinea-pig ileum, cough induced by bradykinin receptor agonist and angiotensin converting enzyme inhibitors, and brain damage after brain edema both in neonatal rat model and in patients with stroke. In the present study, the effect of noscapine on bradykinin-induced constriction of human umbilical artery was investigated. Segments of human umbilical cords were obtained from women with normal full term pregnancies. Concentration-response curves for bradykinin [1-1000 nM] were constructed in the absence and presence of noscapine [1-1000 nM]. To show the specificity of noscapine for bradykinin-induced constriction in the tissue, the effect of noscapine [10 pM] on vasoconstriction produced by histamine were also examined. The results showed that noscapine could antagonize the constriction produced by bradykinin in human umbilical artery. It was also demonstrated that noscapine was capable of reducing histamine-induced contractile response. It is concluded that noscapine can antagonize bradykinin-induced constriction of human umbilical artery in a nonspecific manner. Thus, noscapine is likely to find a clinical application in pathologic conditions accompanied by higher vascular sensitivity to bradykinin in pregnancy