scholarly journals Early Ascorbic Acid Administration Prevents Vascular Endothelial Cell Damage In Septic Mice

Author(s):  
Yutaro Madokoro ◽  
Chinatsu Kamikokuryo ◽  
Shuhei Niiyama ◽  
Takashi Ito ◽  
Satoshi Hara ◽  
...  

Abstract Ascorbic acid (AsA) therapy for sepsis is thought to have a protective effect on vascular endothelial cells, but the effect of AsA therapy on endothelial cell dysfunction over time and the appropriate timing for AsA administration to demonstrate efficacy is unclear. Septic mice, induced by cecal ligation and puncture (CLP), were examined for the effect of AsA administration (200 mg/kg) on vascular endothelial cell dysfunction at two administration timings: early group (AsA was administered immediately after CLP) and late group (AsA was administered 12 h after CLP). Survival rates were compared between the early and late administration groups, and vascular endothelial cell damage, indicated by the dihydrobiopterin/tetrahydrobiopterin ratio, serum syndecan-1, and endothelial nitric oxide synthase, as well as liver damage, were examined. The early group showed significantly improved survival compared to the non-treatment group (p < 0.05), while the late group showed no improved survival compared to the non-treatment group. Early AsA administration suppressed damage to the vascular endothelial system and liver compared to the non-treatment group. In septic mice, early AsA administration immediately after CLP may have protective effects on vascular endothelial cells, resulting in reduced organ dysfunction and improved survival.

2021 ◽  
Author(s):  
Yutaro Madokoro ◽  
Chinatsu Kamikokuryo ◽  
Shuhei Niiyama ◽  
Takashi Ito ◽  
Satoshi Hara ◽  
...  

Abstract Background: Ascorbic acid (AsA) therapy for sepsis is thought to have a protective effect on vascular endothelial cells. However, the effect of AsA therapy on endothelial cell dysfunction over time and the appropriate timing for AsA administration to demonstrate efficacy is unclear.Methods: Septic mice were induced by cecal ligation and puncture (CLP). The effect of AsA administration (200 mg/kg) on vascular endothelial cell dysfunction in sepsis was examined using septic mice at two administration timings: early group (AsA was administered immediately after CLP) and late group (AsA was administered 12 h after CLP). First, survival rates were compared between the early and late administration groups. Next, the dihydrobiopterin/tetrahydrobiopterin (BH2/BH4) ratio, serum syndecan-1, and endothelial nitric oxide synthase (eNOS) were measured as indicators of vascular endothelial cell damage, and liver tissue was examined for organ damage to verify the effect of early AsA administration in septic mice.Results: In survival experiments, the early group showed significantly improved survival compared to the non-treatment group (p < 0.05), while the late group showed no improved survival compared to the non-treatment group. The BH2/BH4 ratio increased after 6 hours following CLP, and the increase was suppressed by early AsA administration (0.12 ± 0.02 vs. 0.07 ± 0.016, p < 0.05). Serum syndecan-1 levels were significantly elevated at 12 h after CLP, and early AsA administration prevented the increase (25.4 ± 12.1 vs. 9.9 ± 2.7 mg/ml, p < 0.05). The expression of eNOS at 12 h after CLP was decreased in the non-treatment group, but the expression was protected by early AsA administration. Moreover, hematoxylin and eosin staining of hepatocytes showed reduced liver damage in the early group compared to the non-treatment group.Conclusions: In septic mice, early AsA administration immediately after CLP may have protective effects on vascular endothelial cells by decreasing the BH2/BH4 ratio, resulting in reduced organ dysfunction and improved survival. To achieve this effect, early administration of AsA is required before BH4 is oxidized.


2020 ◽  
Vol 11 ◽  
Author(s):  
Hong-guang Wang ◽  
Hua Yan ◽  
Chen Wang ◽  
Mi-mi Li ◽  
Xin-ze Lv ◽  
...  

2020 ◽  
Vol 52 (2) ◽  
pp. 180-191 ◽  
Author(s):  
Qiaoli Chen ◽  
Xiaoye Li ◽  
Lingjun Kong ◽  
Qing Xu ◽  
Zi Wang ◽  
...  

Abstract Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.


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