scholarly journals Renoprotective Effects of Nobiletin on High Glucose-Induced Loss of Proximal Tubular Microvilli

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 412-412
Author(s):  
Min kyung Kang ◽  
Dongyeon Kim ◽  
Young-Hee Kang
Keyword(s):  
Proximal Tubule ◽  
High Glucose ◽  
Citrus Fruit ◽  
Cellular Polarity ◽  
Funding Sources ◽  
In Vivo Animal Model ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Abstract Objectives Kidney proximal tubular epithelium has microvillar brush borders, which is critical to renal reabsorption. Hyperglycemia induce change the loss of brush border and cellular polarity, tight junction disruption. Nobiletin is a polymethoxyflavone present in citrus fruit and peels, and has anti-inflammatory effects. This study investigated the renoprotective effects of nobiletin on proximal tubule microvillar ultrastructure and reabsorption under diabetic condition. Methods Human renal proximal tubular epithelial cells (RPTEC) were incubated in a media exposed to 33 mM glucose in the absence and presence of 1–20 μM nobiletin up to 6 days. Antibodies F-actin, villin, cubulin, megalin, SGLT2 and GLUT2 were used for Western blot analysis. The in vivo animal model employed db/db mice orally administrated with 10 mg/kg of nobiletin. Extracts of tissues were subjected to Western blotting or immunohistochemical staining. Results High glucose declined expression of F-actin and villin required for the assembly of proximal tubule microvilli. In addition, the expression of glucose uptake proteins of GLUT2 and SGLT2 was prompted in hyperglycemia. However, nontoxic nobiletin enhanced the expression of F-actin reduced by high glucose, while the elevated expression of the GLUT2 and SGLT2 was attenuated by nobiletin. In the in vivo study, oral administration of 10 mg/kg nobiletin inhibited loss of tubular microvilli through restoring expression of F-actin and villin in diabetic kidneys. Furthermore, nobiletin reduced expressions of GLUT2 and the albumin uptake receptors of cubulin and megalin in db/db mouse kidneys. Conclusions These results demonstrated that nobiletin curtailed loss of the proximal tubular microvillar proteins responsible for tubular reabsorption. Nobiletin may be a potent renoprotective agent counteracting diabetes-associated proximal tubular dysfunctions leading to kidney failure. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (2017R1A6A3A04011473).

In Vitro and In Vivo Evaluation of Amphiphilic Chitosan Derivatives for Inhibition of Organic Cation Transport Function

2020 ◽  
Vol 859 ◽  
pp. 45-50
Author(s):  
Sirima Soodvilai ◽  
Sunhapas Soodvila ◽  
Warayuth Sajomsang ◽  
Theerasak Rojanarata ◽  
Prasopchai Patrojanasophon ◽  
...  
Keyword(s):  
Organic Cation ◽  
Drug Disposition ◽  
Organic Cation Transporter ◽  
Transport Function ◽  
Chitosan Derivatives ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

This study explored the interaction of amphiphilic chitosan derivatives, N-benzyl-N,O-succinyl chitosan (BSCS), N-naphthyl-N,O-succinyl chitosan (NSCS) and N-octyl-N,O-succinyl chitosan (OSCS), with renal organic cation transporter 2 (OCT2). The influence of amphiphilic chitosan derivatives on renal OCT2 transport function was determined by monitoring the transport of a positively charged substrate into human renal proximal tubular epithelial cells (RPTEC/TERT1 cells), and murine kidney. Amphiphilic chitosan derivatives inhibited 3H-MPP (a substrate of OCT2) transport in the renal cells in a concentration-reliance characteristic. OSCS reduced the accumulation of the cationic drug, cisplatin, in RPTEC/TERT1 cells. This effect was more pronounced than that of other chitosan derivatives. In addition, co-administration of cisplatin and OSCS significantly reduced cisplatin accumulation compared with receiving cisplatin alone. This result was accompanied by the decrease in nephrotoxicity induced by cisplatin. In conclusion, OSCS inhibited OCT2 function and reduced cationic drug disposition in human renal proximal tubular cells and murine kidney.

scholarly journals Therapy with antisense TGF-β1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice

2000 ◽  
Vol 278 (4) ◽  
pp. F628-F634 ◽  
Author(s):  
Dong Cheol Han ◽  
Brenda B. Hoffman ◽  
Soon Won Hong ◽  
Jia Guo ◽  
Fuad N. Ziyadeh
Keyword(s):  
Proximal Tubule ◽  
High Glucose ◽  
Leucine Incorporation ◽  
Diabetic Mice ◽  
Renal Hypertrophy ◽  
Kidney Weight ◽  
Cell Hypertrophy ◽  
Proximal Tubular ◽  
Tgf Β1

Inhibition of gene expression by antisense oligodeoxynucleotides (ODNs) relies on their ability to bind complementary mRNA sequences and prevent translation. The proximal tubule is a suitable target for ODN therapy in vivo because circulating ODNs accumulate in the proximal tubule in high concentrations. Because increased proximal tubular transforming growth factor- β1 (TGF-β1) expression may mediate diabetic renal hypertrophy, we investigated the effects of antisense TGF-β1 ODN on the high-glucose-induced proximal tubular epithelial cell hypertrophy in tissue culture and on diabetic renal hypertrophy in vivo. Mouse proximal tubular cells grown in 25 mM d-glucose and exposed to sense ODN as control (1 μM) exhibited increased3[H]leucine incorporation by 120% and total TGF-β1 protein by 50% vs. culture in 5.5 mM d-glucose. Antisense ODN significantly decreased the high-glucose-stimulated TGF-β1 secretion and leucine incorporation. Continuous infusion for 10 days of ODN (100 μg/day) was achieved via osmotic minipumps in diabetic and nondiabetic mice. Sense ODN-treated streptozotocin-diabetic mice had 15.3% increase in kidney weight, 70% increase in α1(IV) collagen and 46% increase in fibronectin mRNA levels compared with nondiabetic mice. Treatment of diabetic mice with antisense ODN partially but significantly decreased kidney TGF-β1 protein levels and attenuated the increase in kidney weight and the α1(IV) collagen and fibronectin mRNAs. In conclusion, therapy with antisense TGF-β1 ODN decreases TGF-β1 production and attenuates high-glucose-induced proximal tubular cell hypertrophy in vitro and partially prevents the increase in kidney weight and extracellular matrix expression in diabetic mice.

scholarly journals Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Blanca Humanes ◽  
Juan Carlos Jado ◽  
Sonia Camaño ◽  
Virginia López-Parra ◽  
Ana María Torres ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Morphological Changes ◽  
Antimicrobial Effect ◽  
Bactericidal Effect ◽  
Mitochondrial Activity ◽  
Protective Effects ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular ◽  
Induced Apoptosis

Vancomycin is a very effective antibiotic for treatment of severe infections. However, its use in clinical practice is limited by nephrotoxicity. Cilastatin is a dehydropeptidase I inhibitor that acts on the brush border membrane of the proximal tubule to prevent accumulation of imipenem and toxicity. The aim of this study was to investigate the potential protective effect of cilastatin on vancomycin-induced apoptosis and toxicity in cultured renal proximal tubular epithelial cells (RPTECs). Porcine RPTECs were cultured in the presence of vancomycin with and without cilastatin. Vancomycin induced dose-dependent apoptosis in cultured RPTECs, with DNA fragmentation, cell detachment, and a significant decrease in mitochondrial activity. Cilastatin prevented apoptotic events and diminished the antiproliferative effect and severe morphological changes induced by vancomycin. Cilastatin also improved the long-term recovery and survival of RPTECs exposed to vancomycin and partially attenuated vancomycin uptake by RPTECs. On the other hand, cilastatin had no effects on vancomycin-induced necrosis or the bactericidal effect of the antibiotic. This study indicates that cilastatin protects against vancomycin-induced proximal tubule apoptosis and increases cell viability, without compromising the antimicrobial effect of vancomycin. The beneficial effect could be attributed, at least in part, to decreased accumulation of vancomycin in RPTECs.

scholarly journals Long term safety of targeted internalization of cell penetrating peptide crotamine into renal proximal tubular epithelial cells in vivo

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joana Darc Campeiro ◽  
Wendy Dam ◽  
Gabriela Guilherme Monte ◽  
Lucas Carvalho Porta ◽  
Lilian Caroline Gonçalves de Oliveira ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Penetrating Peptide ◽  
Tubular Epithelial Cells ◽  
Cell Penetrating ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

scholarly journals High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Daisuke Ogawa ◽  
Masato Asanuma ◽  
Ikuko Miyazaki ◽  
Hiromi Tachibana ◽  
Jun Wada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Vitamin E ◽  
Epithelial Cells ◽  
High Glucose ◽  
Male Rats ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

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