Abstract
This study was conducted to investigate the damage caused by vanadium compounds and to explore the protective effects of berberine (BBR) in human umbilical vein endothelial cells (HUVECs). BBR is a biologically active small molecule found in Coptis rhizome, a remedy used in traditional Chinese medicine to treat diabetes. BBR has also been shown to lower blood glucose in diabetic patients. MTT assay was performed to observe the influence of bis(acetylacetonato)-oxidovanadium [VO(acac)2] or sodium metavanadate (NaVO3) and BBR on viability of HUVECs. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TER). The endothelial nitric oxide synthase (eNOS) activity was detected by ELISA. Flow cytometry was performed to detect the generation of reactive oxygen species (ROS). The results showed that the viability of HUVECs was decreased by treatment with vanadium compounds 50–400 μM in a concentration-dependent manner, while 0.01–1 μM BBR effectively protected HUVECs from the inhibitory effects of vanadium compounds on cell viability. Also 100 and 200 μM VO(acac)2 induced high permeability and decreased eNOS activity in HUVECs. While 0.01–1 μM BBR showed no improvement in the permeability, and failed to reverse the VO(acac)2-induced changes of eNOS activity, but BBR treatment increased the eNOS activity in control cells. The addition of 200 μM VO(acac)2 significantly induced ROS generation in HUVECs, while 0.01 or 0.1 μM BBR reversed the change of ROS. In summary, BBR has protective effects in HUVECs damage induced by vanadium compounds, which is not mediated by eNOS, but related to reduced intracellular ROS.
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Abbreviations
- VO(acac)2 :
-
Bis(acetylacetonato)-oxidovanadium(IV)
- NaVO3 :
-
Sodium metavanadate(V)
- BBR:
-
Berberine
- HUVECs:
-
Human umbilical vein endothelial cells
- MTT:
-
3-(4, 5-Dimethylthiazoyl-2-yl) 2, 5-diphenyltetrazolium bromide
- eNOS:
-
Endothelial nitric oxide synthase
- iNOS:
-
Inducible nitric oxide synthase
- tNOS:
-
Total nitric oxide synthase
- NO:
-
Nitric oxide
- TER:
-
Transendothelial electrical resistance
- ROS:
-
Reactive oxygen species
- DMEM:
-
Dulbecco’s modified eagle medium
- FBS:
-
Fetal bovine serum
- DCFH-DA:
-
2′-7′-Dichlorofluorescein-diacetate
- DMSO:
-
Dimethylsulfoxide
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Acknowledgements
This study is financially supported by the Grants from The Science and Technology Support programs of Hebei Province No. 17967753D, National Nature Science Foundation of China No. 31800975, The Medical Science research project of Hebei Province No. 20190034 and The Science and Technology research project of Hebei higher education institutions No. QN2017104.
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Hou, CC., Liang, HY., Pan, YH. et al. Vanadium compounds induced damage of human umbilical vein endothelial cells and the protective effect of berberine. Biometals 32, 785–794 (2019). https://doi.org/10.1007/s10534-019-00211-6
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DOI: https://doi.org/10.1007/s10534-019-00211-6