scholarly journals Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells

2013 ◽  
Vol 85 (2) ◽  
pp. 745-752 ◽  
Author(s):  
Jyh-Gang Leu ◽  
Chin-Yao Lin ◽  
Jhin-Hao Jian ◽  
Chin-Yu Shih ◽  
Yao-Jen Liang

The anti-oxidant effects of epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG)-induced TNF-α and IL-6 production in human embryonic kidney (HEK) cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE) mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.

2010 ◽  
Vol 299 (5) ◽  
pp. C1212-C1219 ◽  
Author(s):  
W. Bao ◽  
D. Min ◽  
S. M. Twigg ◽  
N. A. Shackel ◽  
F. J. Warner ◽  
...  

CD147 is a highly glycosylated transmembrane protein that is known to play a role in regulation of many protein families. It has the unique ability to maintain functional activity in both the membrane bound state and in the soluble form. CD147 is known to play a role in regulation of matrix metalloproteinase (MMP) expression, but whether its expression is affected by the diabetic milieu is not known, and its role in regulation of monocyte MMPs in this environment has not been investigated. Therefore, in this study we investigated the effect of advanced glycation end products (AGEs) and high glucose (HG; 25 mM), on monocyte CD147 expression. Culture of THP-1 monocytes in the presence of AGEs or HG significantly increased CD147 at the gene and protein level. THP-1 cell results were confirmed using freshly isolated monocytes from human volunteers. The effect of AGEs and HG on CD147 expression was also mimicked by addition of proinflammatory cytokines. Addition of AGEs or HG also increased expression of monocyte MMP-1 and MMP-9 but not MMP-2. This increase in MMPs was significantly attenuated by inhibition of CD147 using either a small interfering RNA or an anti-CD147 antibody. Inhibition of NF-κB or addition of antibodies to either TNF-α or the receptor for AGE (RAGE) each significantly prevented in a dose-dependent manner the induction of CD147 gene and protein by AGE and also decreased MMP-1 and MMP-9. This novel result shows that AGEs can induce monocyte CD147 expression, an effect mediated by inflammatory pathways and RAGE. Because MMPs play a role in monocyte migration, inhibition of their regulator CD147 may assist in the prevention of diabetic complications, particularly those where monocyte infiltration is an early initiating event.


2021 ◽  
Vol 14 (7) ◽  
pp. 965-972
Author(s):  
Qing Liu ◽  
◽  
Hong Yan ◽  

AIM: To study the effect of thioltransferase (TTase) on oxidative stress in human lens epithelial cells (HLECs) induced by high glucose and advanced glycation end products (AGEs). METHODS: HLECs were treated with 35.5 mmol/L glucose or 1.5 mg/mL AGEs modified bovine serum albumin (AGEs-BSA) as the experimental groups, respectively. Cells were collected at the time point of 1, 2, 3, and 4d. The TTase activity were measured accordingly. TTase mRNA levels were detected by quantitative reverse transcription polymerase chain response (qRT-RCR) and its protein level was detected by Western blot. The siRNA was used to knock down the expression of TTase. The activity of catalase (CAT) and superoxide dismutase (SOD), the content of reactive oxygen species (ROS) and the ratio of oxidized glutathione/total glutathione (GSSG/T-GSH) were assessed in different groups, respectively. RESULTS: The level of TTase mRNA gradually increased and reached the top at 2d, then it decreased to the normal level at 4d, and the TTase activity increased from 2 to 3d in both high glucose and AGEs-BSA groups. The TTase expression elevated from 2d in high glucose group, and it began to rise from 3d in AGEs-BSA group. The activity of CAT and SOD showed a decrease and the content of ROS and the ratio of GSSG/T-GSH showed an increase in high glucose and AGEs-BSA group. These biochemical alterations were more prominent in the groups with TTase siRNA. CONCLUSION: High glucose and AGEs can increase ROS content in HLECs; therefore, it induces oxidative stress. This may result in the decreased GSH and increased GSSG content, impaired activity of SOD and CAT. The up-regulated TTase likely provides oxidation damage repair induced by high glucose and AGEs in the early stage.


2013 ◽  
Vol 83 (2) ◽  
pp. 77-85 ◽  
Author(s):  
Nazanin Noori ◽  
Hadi Tabibi ◽  
Farhad Hosseinpanah ◽  
Mehdi Hedayati ◽  
Mohsen Nafar

This study was designed to investigate the effects of combined administration of lipoic acid and pyridoxine on albuminuria, oxidative stress, blood pressure, serum advanced glycation end-products, nitric oxide (NO), and endothelin-1 in patients with diabetic nephropathy. Thirty-four patients were randomly assigned to either a supplement group or a placebo group. The patients in the supplement group received 800 mg lipoic acid and 80 mg pyridoxine daily for 12 weeks, whereas the placebo group received corresponding placebos. Urinary albumin, serum malondialdehyde (MDA), and systolic blood pressure decreased significantly in the supplement group compared to the placebo group (p < 0.05). Serum NO increased in the supplement group compared to the placebo group (p < 0.05). Serum pentosidine and carboxymethyl lysine decreased significantly in the supplement group at the end of week 12 compared to baseline (p < 0.05). No statistically significant differences were observed between the two groups in mean changes of serum endothelin-1, glucose, and diastolic blood pressure. The present study indicates that combined administration of lipoic acid and pyridoxine improves albuminuria in patients with diabetic nephropathy by reducing oxidative stress, advanced glycation end-products, and systolic blood pressure. The reduction in microalbuminuria may be of benefit in retarding the progression of diabetic nephropathy.


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