scholarly journals Titanium Dioxide Nanoparticles Enhance Leakiness and Drug Permeability in Primary Human Hepatic Sinusoidal Endothelial Cells

2018 ◽  
Vol 20 (1) ◽  
pp. 35 ◽  
Author(s):  
Jie Tee ◽  
Li Ng ◽  
Hannah Koh ◽  
David Leong ◽  
Han Ho

Liver sinusoidal endothelial cells (LSECs) represent the permeable interface that segregates the blood compartment from the hepatic cells, regulating hepatic vascular tone and portal pressure amidst changes in the blood flow. In the presence of pathological conditions, phenotypic changes in LSECs contribute to the progression of chronic liver diseases, including the loss of endothelial permeability. Therefore, modulating LSECs offers a possible way to restore sinusoidal permeability and thereby improve hepatic recovery. Herein, we showed that titanium dioxide nanoparticles (TiO2 NPs) could induce transient leakiness in primary human hepatic sinusoidal endothelial cells (HHSECs). Interestingly, HHSECs exposed to these NPs exhibited reduced protein kinase B (Akt) phosphorylation, an important protein kinase which regulates cell attachment. Using a 3D co-culture system, we demonstrated that TiO2 NPs diminished the attachment of HHSECs onto normal human hepatic cell LO2. To further illustrate the significance of leakiness in liver sinusoids, we showed that NP-induced leakiness promoted Sunitinib transport across the HHSEC layer, resulting in increased drug uptake and efficacy. Hence, TiO2 NPs have the potential to modulate endothelial permeability within the specialized sinusoidal endothelium, especially during events of fibrosis and occlusion. This study highlighted the possible use of inorganic NPs as a novel strategy to promote drug delivery targeting the diseased liver.

2013 ◽  
Vol 305 (2) ◽  
pp. G163-G171 ◽  
Author(s):  
Songling Liu ◽  
Don C. Rockey

The function of the endothelial isoform of nitric oxide synthase (eNOS) and production of nitric oxide (NO) is altered in a number of disease states. Pharmacological approaches to enhancing NO synthesis and thus perhaps endothelial function could have substantial benefits in patients. We analyzed the effect of cicletanine, a synthetic pyridine with potent vasodilatory characteristics, on eNOS function and NO production in normal (liver) and injured rat sinusoidal endothelial cells, and we studied the effect of cicletanine-induced NO on stellate cell contraction and portal pressure in an in vivo model of liver injury. Sinusoidal endothelial cells were isolated from normal and injured rat livers. After exposure to cicletanine, eNOS phosphorylation, NO synthesis, and the signaling pathway regulating eNOS activation were measured. Cicletanine led to an increase in eNOS (Ser1177) phosphorylation, cytochrome c reductase activity, l-arginine conversion to l-citrulline, as well as NO production. The mechanism of the effect of cicletanine appeared to be via the protein kinase B (Akt) and MAP kinase/Erk signaling pathways. Additionally, cicletanine improved NO synthesis in injured sinusoidal endothelial cells. NO production induced by cicletanine in sinusoidal endothelial cells increased protein kinase G (PKG) activity as well as relaxation of stellate cells. Finally, administration of cicletanine to mice with portal hypertension induced by bile duct ligation led to reduction of portal pressure. The data indicate that cicletanine might improve eNOS activity in injured sinusoidal endothelial cells and likely activates hepatic stellate cell NO/PKG signaling. It raises the possibility that cicletanine could improve intrahepatic vascular function in portal hypertensive patients.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 4090
Author(s):  
Morteza Sheikhalipour ◽  
Behrooz Esmaielpour ◽  
Gholamreza Gohari ◽  
Maryam Haghighi ◽  
Hessam Jafari ◽  
...  

High salt levels are one of the significant and major limiting factors on crop yield and productivity. Out of the available attempts made against high salt levels, engineered nanoparticles (NPs) have been widely employed and considered as effective strategies in this regard. Of these NPs, titanium dioxide nanoparticles (TiO2 NPs) and selenium functionalized using chitosan nanoparticles (Cs–Se NPs) were applied for a quite number of plants, but their potential roles for alleviating the adverse effects of salinity on stevia remains unclear. Stevia (Stevia rebaudiana Bertoni) is one of the reputed medicinal plants due to their diterpenoid steviol glycosides (stevioside and rebaudioside A). For this reason, the current study was designed to investigate the potential of TiO2 NPs (0, 100 and 200 mg L−1) and Cs–Se NPs (0, 10 and 20 mg L−1) to alleviate salt stress (0, 50 and 100 mM NaCl) in stevia. The findings of the study revealed that salinity decreased the growth and photosynthetic traits but resulted in substantial cell damage through increasing H2O2 and MDA content, as well as electrolyte leakage (EL). However, the application of TiO2 NPs (100 mg L−1) and Cs–Se NPs (20 mg L−1) increased the growth, photosynthetic performance and activity of antioxidant enzymes, and decreased the contents of H2O2, MDA and EL under the saline conditions. In addition to the enhanced growth and physiological performance of the plant, the essential oil content was also increased with the treatments of TiO2 (100 mg L−1) and Cs–Se NPs (20 mg L−1). In addition, the tested NPs treatments increased the concentration of stevioside (in the non-saline condition and under salinity stress) and rebaudioside A (under the salinity conditions) in stevia plants. Overall, the current findings suggest that especially 100 mg L−1 TiO2 NPs and 20 mg L−1 Cs–Se could be considered as promising agents in combating high levels of salinity in the case of stevia.


Nanoscale ◽  
2020 ◽  
Author(s):  
Yanjun Gao ◽  
Tingyu Li ◽  
Shuming Duan ◽  
Lizhi Lv ◽  
Yuan Li ◽  
...  

Titanium dioxide nanoparticles (TiO2-NPs) is widely applicated as additives in foods for its excellent whitening and brightening capability. Although the toxicity and antibacterial activity of TiO2-NPs has been extensively studied,...


PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0188169 ◽  
Author(s):  
Angélica Montiel-Dávalos ◽  
Guadalupe Jazmin Silva Sánchez ◽  
Elizabeth Huerta-García ◽  
Cristhiam Rueda-Romero ◽  
Giovanny Soca Chafre ◽  
...  

2019 ◽  
Vol 34 (11) ◽  
pp. 1199-1207 ◽  
Author(s):  
Fen Liao ◽  
Lingying Chen ◽  
Yuanfeng Liu ◽  
Dongting Zhao ◽  
Wenyi Peng ◽  
...  

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