scholarly journals How Does Glycation Affect Binding Parameters of the Albumin-Gliclazide System in the Presence of Drugs Commonly Used in Diabetes? In Vitro Spectroscopic Study

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3869
Author(s):  
Katarzyna Wiglusz ◽  
Ewa Żurawska-Płaksej ◽  
Anna Rorbach-Dolata ◽  
Agnieszka Piwowar

In this research, the selected drugs commonly used in diabetes and its comorbidities (gliclazide, cilazapril, atorvastatin, and acetylsalicylic acid) were studied for their interactions with bovine serum albumin—native and glycated. Two different spectroscopic methods, fluorescence quenching and circular dichroism, were utilized to elucidate the binding interactions of the investigational drugs. The glycation process was induced in BSA by glucose and was confirmed by the presence of advanced glycosylation end products (AGEs). The interaction between albumin and gliclazide, with the presence of another drug, was confirmed by calculation of association constants (0.11–1.07 × 104 M−1). The nature of changes in the secondary structure of a protein depends on the drug used and the degree of glycation. Therefore, these interactions may have an influence on pharmacokinetic parameters.

2020 ◽  
Vol 15 (1) ◽  
pp. 619-628
Author(s):  
Chen Yuan ◽  
Ya Mo ◽  
Jie Yang ◽  
Mei Zhang ◽  
Xuejun Xie

AbstractAdvanced glycosylation end products (AGEs) are harmful factors that can damage the inner blood–retinal barrier (iBRB). Rat retinal microvascular endothelial cells (RMECs) were isolated and cultured, and identified by anti-CD31 and von Willebrand factor polyclonal antibodies. Similarly, rat retinal Müller glial cells (RMGCs) were identified by H&E staining and with antibodies of glial fibrillary acidic protein and glutamine synthetase. The transepithelial electrical resistance (TEER) value was measured with a Millicell electrical resistance system to observe the leakage of the barrier. Transwell cell plates for co-culturing RMECs with RMGCs were used to construct an iBRB model, which was then tested with the addition of AGEs at final concentrations of 50 and 100 mg/L for 24, 48, and 72 h. AGEs in the in vitro iBRB model constructed by RMEC and RMGC co-culture led to the imbalance of the vascular endothelial growth factor (VEGF) and pigment epithelial derivative factor (PEDF), and the permeability of the RMEC layer increased because the TEER decreased in a dose- and time-dependent manner. AGEs increased VEGF but lowered PEDF in a dose- and time-dependent manner. The intervention with AGEs led to the change of the transendothelial resistance of the RMEC layer likely caused by the increased ratio of VEGF/PEDF.


Author(s):  
Qingxian Li ◽  
Yinxian Wen ◽  
Linlong Wang ◽  
Biao Chen ◽  
Jun Chen ◽  
...  

AbstractOsteoarthritis (OA) is significantly associated with diabetes, but how hyperglycemia induces or aggravates OA has not been shown. The synovium plays a critical role in cartilage metabolism and substance exchange. Herein, we intended to investigate whether and how hyperglycemia affects the occurrence and progression of OA by influencing the synovium. In patients with knee OA and diabetes (DM OA), we found a more severe inflammatory response, higher endoplasmic reticulum stress (ERS) levels, and more advanced glycosylation end products (AGEs) accumulation in the synovium than in patients without diabetes. Subsequently, we found similar results in the DM OA group in a rat model. In the in vitro cocultivation system, high glucose-stimulated AGEs accumulation, ERS, and inflammation in rat fibroblast-like synoviocytes (FLSs), which resulted in chondrocyte degeneration due to inflammatory factors from FLSs. Furthermore, in the synovium of the DM OA group and FLSs treated with high glucose, the expression of glucose transporter 1 (GLUT1) and its regulatory factor hypoxia-inducible factor (HIF)-1α was increased significantly. Inhibitors of HIF-1α, GLUT1 or AGEs receptors attenuated the effect of high glucose on chondrocyte degradation in the FLS-chondrocyte coculture system. In summary, we demonstrated that hyperglycemia caused AGEs accumulation in FLSs via the HIF-1α-GLUT1 pathway, which increases the release of inflammatory factors from FLSs, subsequently inducing chondrocyte degradation and promoting OA progression.


2020 ◽  
Author(s):  
Chen Yuan ◽  
Ya Mo ◽  
Jie Yang ◽  
Mei Zhang ◽  
Xuejun Xie

Abstract Background: Advanced glycosylation end products (AGEs) are harmful factors that can damage the inner blood-retinal barrier (iBRB). However, their effects on iBRB co-culture models in vitro have not been reported. This study is to understand the interactive effects of different concentrations of AGEs at different time points on rat retinal microvascular endothelial cells (RMEC) and rat retinal Müller glial cell (RMGC) co-culture models. Methods: RMEC of Sprague-Dawley rat was isolated and cultured, identified by anti-CD31 flow cytometry and immunocytometry with von Willebrand factor polyclonal antibody. Similarly, RMGC of Sprague-Dawley rat was identified by H&E staining, and immunohistochemical method with antibodies of Glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). The transepithelial electrical resistance (TEER) value was measured with the Millicell electrical resistance system to observe the leakage of the barrier. The Transwell cell for co-cultured RMEC with RMGC were used to construct an iBRB model and tested with the addition of AGEs at final concentrations of 50 mg/L and 100 mg/L, respectively, for 24 hours, 48 hours, and 72 hours.Results: AGEs in vitro iBRB model constructed by RMEC and RMGC co-culture led to the imbalance of VEGF and PEDF, and the permeability of the RMEC layer increased because TEER decreased in a dose- and time-dependent manner. In the AGEs intervention the vascular endothelial growth factor (VEGF) was increased, while pigment epithelial derivative factor (PEDF) decreased, respectively, in a dose- and time-dependent manner by enzyme-linked immunosorbent assay.Conclusions: The intervention with AGEs led to change of the RMEC layer transendothelial resistance and ratio of VEGF/PEDF. The iBRB in vitro model is a good tool to study the pathogenesis of retinal vascular diseases such as diabetic retinopathy and to evaluate the candidate drugs on the diseases.


1991 ◽  
Vol 325 (12) ◽  
pp. 836-842 ◽  
Author(s):  
Zenji Makita ◽  
Steven Radoff ◽  
Elliot J. Rayfield ◽  
Zhi Yang ◽  
Edward Skolnik ◽  
...  

1995 ◽  
Vol 48 (1) ◽  
pp. 111-117 ◽  
Author(s):  
Douglas C. Throckmorton ◽  
Anne P. Brogden ◽  
Brian Min ◽  
Howard Rasmussen ◽  
Michael Kashgarian

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