scholarly journals Effect of Cysteine on Methylglyoxal-Induced Renal Damage in Mesangial Cells

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 234 ◽  
Author(s):  
Jae Hyuk Lee ◽  
Lalita Subedi ◽  
Sun Yeou Kim
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Damage ◽  
Mesangial Cells ◽  
Protective Effects ◽  
Advanced Glycation ◽  
Dicarbonyl Compound ◽  
Glycation End Products ◽  
Induced Apoptosis ◽  
Apoptosis And Necrosis ◽  
Potential Use

Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. The activation of glyoxalase-I (GLO-I) increases MGO and MGO-AGE detoxification. MGO-mediated glucotoxicity can also be ameliorated by MGO scavengers such as N-acetylcysteine (NAC), aminoguanidine (AG), and metformin. In this study, we noted that l-cysteine demonstrated protective effects against MGO-induced glucotoxicity in renal mesangial cells. l-cysteine prevented MGO-induced apoptosis and necrosis, together with a reduction of reactive oxygen species (ROS) production in MES13 cells. Interestingly, l-cysteine significantly reduced MGO-AGE formation and also acted as an MGO-AGE crosslink breaker. Furthermore, l-cysteine treatment accelerated MGO catabolism to D-lactate via the upregulation of GLO-I. The reduction of AGE formation and induction of AGE breakdown, following l-cysteine treatment, further supports the potential use of l-cysteine as an alternative for the therapeutic control of MGO-induced renal complications in diabetes, especially against diabetic nephropathy.

scholarly journals 3′-O-β-d-glucopyranosyl-α,4,2′,4′,6′-pentahydroxy-dihydrochalcone, from Bark of Eysenhardtia polystachya Prevents Diabetic Nephropathy via Inhibiting Protein Glycation in STZ-Nicotinamide Induced Diabetic Mice

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1214 ◽  
Author(s):  
Rosa Pérez Gutierrez ◽  
Abraham García Campoy ◽  
Silvia Paredes Carrera ◽  
Alethia Muñiz Ramirez ◽  
José Mota Flores ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Advanced Glycation End Products ◽  
Renal Damage ◽  
Histological Analysis ◽  
Protein Glycation ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3′-O-β-d-glucopyranosyl α,4,2′,4′,6′-pentahydroxy–dihydrochalcone (1) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya. The aim was to investigate whether (1) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly (p < 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly (p < 0.05) attenuated by (1) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound (1) attenuated the renal damage in diabetic mice by inhibiting AGEs formation.

scholarly journals Protective Effects of Broussonetia kazinoki Siebold Fruit Extract against Palmitate-Induced Lipotoxicity in Mesangial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Donghee Kim ◽  
Hyo-Jin Kim ◽  
Seon-Heui Cha ◽  
Hee-Sook Jun
Keyword(s):  
Diabetic Nephropathy ◽  
Antioxidant Enzymes ◽  
Protective Effect ◽  
Mesangial Cells ◽  
Ethanolic Extract ◽  
Protective Effects ◽  
Glomerular Mesangial Cells ◽  
Apoptotic Genes ◽  
Stress Related Genes ◽  
Induced Apoptosis

Diabetic nephropathy is one of the most serious complications of diabetes. Lipotoxicity in glomerular mesangial cells is associated with the progression of diabetic nephropathy. Paper mulberry, Broussonetia kazinoki Siebold (BK), has been used in oriental medicine for human health problems. However, to date, the beneficial effect of BK fruit has not been studied. In this study, we investigated the protective effect of an ethanolic extract of BK fruit (BKFE) against palmitate- (PA-) induced toxicity in mesangial cells. BKFE significantly increased the viability of PA-treated SV40 MES13 cells. BKFE significantly inhibited PA-induced apoptosis and decreased the expression of apoptotic genes, cleaved caspase-3, and cleaved PARP. Moreover, BKFE inhibited the expression of endoplasmic reticulum (ER) stress-related genes, such as BiP, phosphorylated eIF2α, cleaved ATF6, and spliced XBP-1, in PA-treated SV40 MES13 cells. BKFE decreased PA-induced ROS production. In addition, BKFE activated the transcription factor Nrf2 and increased the expression of antioxidant enzymes. However, knockdown of Nrf2 using siRNA suppressed this BKFE-induced increase in antioxidant enzyme expression. Furthermore, the protective effect of BKFE on PA-induced apoptosis was significantly reduced by Nrf2 knockdown. In conclusion, BKFE induced the expression of antioxidant enzymes via activation of Nrf2 and protected against PA-induced lipotoxicity in mesangial cells.

scholarly journals DJC Suppresses Advanced Glycation End Products-Induced JAK-STAT Signaling and ROS in Mesangial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Min Sun ◽  
Yan Li ◽  
Wenjie Bu ◽  
Jindong Zhao ◽  
Jianliang Zhu ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Advanced Glycation End Products ◽  
Oxidase Activity ◽  
Mesangial Cells ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Nadph Oxidase Activity ◽  
Glycation End Products ◽  
End Products ◽  
Anti Inflammatory

The antidiabetic properties and anti-inflammatory effects of Danzhi Jiangtang Capsules (DJC) have been demonstrated in clinical and laboratory experiments. In this study, we explored whether DJC can ameliorate advanced glycation end products- (AGEs-) mediated cell injury and the precise mechanisms of DJC in treating diabetic nephropathy (DN). Western blot analysis was employed to assess the expressions of iNOS, COX2, and SOCS and the phosphorylation of JAK2, STAT1, and STAT3 in glomerular mesangial cells (GMCs) after treatment with DJC. TNF-α, IL-6, and MCP-1 were determined using double-antibody sandwich ELISA. ROS and NADPH oxidase activity were measured by DCFH-DA assay and lucigenin-enhanced chemiluminescence, respectively. DJC significantly reversed the AGEs-induced expression of COX2 and iNOS. Moreover, DJC inhibited the AGEs-induced JAK2-STAT1/STAT3 activation, resulting in the inhibition of inflammatory cytokines such as IL-6, MCP-1, and TNF-αin a concentration-dependent manner. The ability of DJC to suppress STAT activation was also verified by the observation that DJC significantly increased the SOCS3 protein level. DJC reversed the AGEs-induced accumulation of ROS and NADPH oxidase activity, thus confirming that DJC possesses antioxidant activity. The results suggest that the anti-inflammatory effects of DJC in GMCs may be due to its ability to suppress the JAK2-STAT1/STAT3 cascades and reduce ROS production.

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