scholarly journals VERNONIA CINEREA (NEICHITTI KEERAI) REGENERATES PROXIMAL TUBULES IN CISPLATININDUCED RENAL DAMAGE IN MICE

2019 ◽  
Vol 12 (1) ◽  
pp. 332 ◽  
Author(s):  
Arul Amuthan ◽  
Vasudha Devi ◽  
Chandrashekara Shastry Shreedhara ◽  
Venkata Rao ◽  
Kunal Puri ◽  
...  
Keyword(s):  
Renal Damage ◽  
Tubular Damage ◽  
Aqueous Fraction ◽  
Renal Tubular Cells ◽  
Damage Grade ◽  
Proximal Tubular ◽  
Proximal Tubular Damage ◽  
Grade 3 ◽  
Renal Tubular ◽  
Vernonia Cinerea

Objective: The aim of the study was to evaluate whether Vernonia cinerea (VC) regenerates the proximal renal tubular cells in cisplatin-induced necrosis in male Swiss albino mice.Methods: The crude aqueous extract (CAE) of VC was fractionated from non-polar to polar using different solvents. Mice were injected a single dose of cisplatin (15 mg/kg) on day 1, which took 5 days to cause maximal renal damage. From day 6, CAE and all fractions were orally administered (200, 300, and 400 mg/kg) for 5 continuous days. On day 11, blood was collected to estimate urea and creatinine. Kidney was collected for histology and grading was done.Results: Cisplatin induced proximal renal tubular damage (grade 5) in corticomedullary junction, characterized by necrosis, proximal tubular dilatation, inflammation and vasodilation. Aqueous fraction (AF) did not show any regeneration; whereas, 400 mg/kg dose of CAE and butanol fraction (BF) showed a significant reduction (p<0.001) in proximal tubular damage (Grade 3) and 50–75% regeneration of proximal tubular epithelial cells.Conclusion: This is the first study to demonstrate the regenerative potential of Neichitti kashayam (CAE of VC) and its BF in cisplatin-induced proximal tubular damage in kidney. Further study is warranted to find out the dose regimen for complete regeneration, lead compounds, and molecular mechanism.

scholarly journals VERNONIA CINEREA (NEICHITTI KEERAI) REGENERATES PROXIMAL TUBULES IN CISPLATININDUCED RENAL DAMAGE IN MICE

2019 ◽  
Vol 12 (1) ◽  
pp. 332
Author(s):  
Arul Amuthan ◽  
Vasudha Devi ◽  
Chandrashekara Shastry Shreedhara ◽  
Venkata Rao ◽  
Kunal Puri ◽  
...  
Keyword(s):  
Renal Damage ◽  
Tubular Damage ◽  
Aqueous Fraction ◽  
Renal Tubular Cells ◽  
Damage Grade ◽  
Proximal Tubular ◽  
Proximal Tubular Damage ◽  
Grade 3 ◽  
Renal Tubular ◽  
Vernonia Cinerea

Objective: The aim of the study was to evaluate whether Vernonia cinerea (VC) regenerates the proximal renal tubular cells in cisplatin-induced necrosis in male Swiss albino mice.Methods: The crude aqueous extract (CAE) of VC was fractionated from non-polar to polar using different solvents. Mice were injected a single dose of cisplatin (15 mg/kg) on day 1, which took 5 days to cause maximal renal damage. From day 6, CAE and all fractions were orally administered (200, 300, and 400 mg/kg) for 5 continuous days. On day 11, blood was collected to estimate urea and creatinine. Kidney was collected for histology and grading was done.Results: Cisplatin induced proximal renal tubular damage (grade 5) in corticomedullary junction, characterized by necrosis, proximal tubular dilatation, inflammation and vasodilation. Aqueous fraction (AF) did not show any regeneration; whereas, 400 mg/kg dose of CAE and butanol fraction (BF) showed a significant reduction (p<0.001) in proximal tubular damage (Grade 3) and 50–75% regeneration of proximal tubular epithelial cells.Conclusion: This is the first study to demonstrate the regenerative potential of Neichitti kashayam (CAE of VC) and its BF in cisplatin-induced proximal tubular damage in kidney. Further study is warranted to find out the dose regimen for complete regeneration, lead compounds, and molecular mechanism.

Longterm treatment of psoriasis using fumaric acid preparations can be associated with severe proximal tubular damage

1999 ◽  
Vol 18 (12) ◽  
pp. 738-739 ◽  
Author(s):  
C Raschka ◽  
H J Koch
Keyword(s):  
Side Effects ◽  
Effective Treatment ◽  
Fumaric Acid ◽  
Renal Damage ◽  
Clinical Laboratory ◽  
Tubular Damage ◽  
Longterm Treatment ◽  
Proximal Tubular ◽  
Proximal Tubular Damage

Fumaric acid preparations are used as longterm and effective treatment of psoriasis. Apart from gastrointestinal, dermatological and hematological side-effects, transient renal damage was observed during treatment with fumaric acid. The case of a 38 year old woman who was treated with fumaric acid (420 mg bid) for 5 years before she complained of fatigue and weakness. According to clinical laboratory she had developed severe proximal tubular damage. Hypophosphatemia, glycosuria and proteinuria persisted although medication was stopped immediately.

scholarly journals Tenofovir and Severe Symptomatic Hypophosphatemia

2019 ◽  
Vol 7 ◽  
pp. 232470961984879 ◽  
Author(s):  
Asim Kichloo ◽  
Savneek Singh Chugh ◽  
Sanjeev Gupta ◽  
Jay Panday ◽  
Ghazaleh Goldar
Keyword(s):  
Renal Damage ◽  
Organic Anion ◽  
Significant Risk ◽  
Anion Transporters ◽  
Immunodeficiency Virus ◽  
Tubular Lumen ◽  
Associated Proteins ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Initial Results

Tenofovir is a broadly used drug used for the treatment of human immunodeficiency virus (HIV). Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria. It is both filtered in the glomerulus and actively secreted in the tubules for elimination and is excreted unchanged in the urine. Studies have shown an active transportation of 20-30% of this drug into the renal proximal tubule (PCT) cells via the organic anion transporters in the baso-lateral membrane (primarily hOAT1, and OAT3 to a lesser extent) and ultimate excretion of the drug into the tubular lumen via the transporters in the proximal tubular apical membrane MRP4 and MRP2 (multidrug resistance-associated proteins 2 & 4). Subsequently, the mitochondrial injury caused by Tenofovir can lead to the development of Fanconi’s syndrome which causes renal tubular acidosis, phosphaturia, aminoaciduria, glucosuria with normoglycemia, and tubular proteinuria. Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.

New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A

2004 ◽  
Vol 18 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Alessandra Gennari ◽  
Patricia Pazos ◽  
Monica Boveri ◽  
Robert Callaghan ◽  
Juan Casado ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Tubular Damage ◽  
Proximal Tubular ◽  
Proximal Tubular Damage ◽  
Renal Proximal Tubular

scholarly journals Palmitate aggravates proteinuria-induced cell death and inflammation via CD36-inflammasome axis in the proximal tubular cells of obese mice

2018 ◽  
Vol 315 (6) ◽  
pp. F1720-F1731 ◽  
Author(s):  
Lung-Chih Li ◽  
Jenq-Lin Yang ◽  
Wen-Chin Lee ◽  
Jin-Bor Chen ◽  
Chien-Te Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Tubular Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Caspase 1 ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Nlrp3 Inflammasomes

High levels of serum free fatty acids (FFAs) and proteinuria have been implicated in the pathogenesis of obesity-related nephropathy. CD36, a class B scavenger receptor, is highly expressed in the renal proximal tubules and mediates FFA uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation. In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA-induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL/6 mice and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro models. Immunohistochemical staining showed that CD36, IL-1β, and IL-18 levels increased progressively in the kidneys of HFD-fed mice. Sulfo- N-succinimidyl oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3, IL-1β, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL-1β, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment with SSO and the knockdown of caspase-1 expression by siRNA both inhibited palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate causes renal tubular inflammation, cell death, and apoptosis via the CD36/NLRP3/caspase-1 axis, which may explain, at least in part, the mechanism underlying FFA-related renal tubular injury. The blockade of CD36-induced cellular processes is therefore a promising strategy for treating obesity-related nephropathy.

scholarly journals Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function

2013 ◽  
Vol 305 (6) ◽  
pp. F881-F890 ◽  
Author(s):  
Hasiyeti Maimaitiyiming ◽  
Yanzhang Li ◽  
Wenpeng Cui ◽  
Xiaopeng Tong ◽  
Heather Norman ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tubular Damage ◽  
Dependent Protein Kinase ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Renal Tubular

Cisplatin is widely used to treat malignancies. However, its major limitation is the development of dose-dependent nephrotoxicity. The precise mechanisms of cisplatin-induced kidney damage remain unclear, and the renoprotective agents during cisplatin treatment are still lacking. Here, we demonstrated that the expression and activity of cGMP-dependent protein kinase-I (PKG-I) were reduced in cisplatin-treated renal tubular cells in vitro as well as in the kidney tissues from cisplatin-treated mice in vivo. Increasing PKG activity by both pharmacological and genetic approaches attenuated cisplatin-induced kidney cell apoptosis in vitro. This was accompanied by decreased Bax/Bcl2 ratio, caspase 3 activity, and cytochrome c release. Cisplatin-induced mitochondria membrane potential loss in the tubular cells was also prevented by increased PKG activity. All of these data suggest a protective effect of PKG on mitochondria function in renal tubular cells. Importantly, increasing PKG activity pharmacologically or genetically diminished cisplatin-induced tubular damage and preserved renal function during cisplatin treatment in vivo. Mitochondria structural and functional damage in the kidney from cisplatin-treated mice was inhibited by increased PKG activity. In addition, increasing PKG activity enhanced ciaplatin-induced cell death in several cancer cell lines. Taken together, these results suggest that increasing PKG activity may be a novel option for renoprotection during cisplatin-based chemotherapy.

Analgesic use of inhaled methoxyflurane

2015 ◽  
Vol 35 (1) ◽  
pp. 91-100 ◽  
Author(s):  
AD Dayan
Keyword(s):  
Clinical Experience ◽  
Renal Damage ◽  
Safety Margin ◽  
Tubular Damage ◽  
Fluoride Ions ◽  
Fluoride Level ◽  
Tubular Toxicity ◽  
Renal Tubular ◽  
Higher Doses ◽  
Analgesic Use

Methoxyflurane is a volatile, halogenated analgesic, self-administered in a controlled low dose from the Penthrox® inhaler for short-term pain relief. It was formerly used in significantly higher doses to produce anaesthesia, when it caused a specific type of dose-related renal tubular damage. The pathogenesis of the renal damage and clinical use of methoxyflurane are discussed here with evidence that a low but effective analgesic dose is not associated with the risk of renal adverse effects. The maximum dose employed to produce analgesia is limited to methoxyflurane 6 mL/day and 15 mL/week, producing a minimum alveolar concentration (MAC) of 0.59 MAC-hours. Renal damage is due to the metabolism of methoxyflurane and release of fluoride ions. Exposure of humans to methoxyflurane ≤2.0 MAC-hours, resulting in serum fluoride ≤40 µmol/L, has not been associated with renal tubular toxicity. The safety margin of analgesic use of methoxyflurane in the Penthrox® inhaler is at least 2.7- to 8-fold, based on methoxyflurane MAC-hours or serum fluoride level, with clinical experience suggesting it is higher. It is concluded from clinical experience in emergency medicine, surgical procedures and various experimental and laboratory investigations that the analgesic use of methoxyflurane in subanaesthetic doses in the Penthrox inhaler does not carry a risk of nephrotoxicity.

Neuropeptide Y shifts equilibrium between α- and β-adrenergic tonus in proximal tubule cells

1998 ◽  
Vol 275 (1) ◽  
pp. F1-F7 ◽  
Author(s):  
Ulla Holtbäck ◽  
Yoshiyuki Ohtomo ◽  
Petter Förberg ◽  
Bo Sahlgren ◽  
Anita Aperia
Keyword(s):  
Atpase Activity ◽  
Neuropeptide Y ◽  
Sympathetic Nerves ◽  
Renal Tissue ◽  
Adrenergic Agonists ◽  
Renal Tubular Cells ◽  
Dependent Inhibition ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Renal Sympathetic

Renal sympathetic nerves play a central role in the regulation of tubular Na+ reabsorption. Norepinephrine (NE) and neuropeptide Y (NPY) are colocalized in renal sympathetic nerve endings. The purpose of this study is to examine the integrated effects of these neurotransmitters on the regulation of Na+-K+-ATPase, the enzyme responsible for active Na+ reabsorption in renal tubular cells. Studies were performed on proximal tubular segments, which express adrenergic α- and β-receptors, as well as NPY-Y2 receptors. It was found that α- and β-adrenergic agonists had opposing effects on Na+-K+-ATPase activity. β-Adrenergic agonists induced a dose-dependent inhibition of the Na+-K+-ATPase activity, whereas α-adrenergic agonists stimulated the enzyme. NPY abolished β-agonist-induced deactivation of Na+-K+-ATPase and enhanced α-agonist-induced activation of Na+-K+-ATPase. The β-adrenergic agonist appeared to inhibit Na+-K+-ATPase activity via a cAMP pathway. NPY antagonized β-agonist-induced accumulation of cAMP. In our preparation, NE alone had no net effect but stimulated the Na+-K+-ATPase activity in the presence of β-adrenergic antagonists, as well as in the presence of NPY. The results indicate that, in renal tissue, NPY determines the net effect of its colocalized transmitter, NE, by its ability to attenuate the β- and enhance the α-adrenergic effect.

Abstract 210: Stem Cell Conditioned Culture Media Attenuated Albumin-induced Epithelial-mesenchymal Transition in Renal Tubular Cells

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Junping Hu ◽  
Weiqing Han ◽  
Qing Zhu ◽  
Pin-Lan Li ◽  
Ningjun Li
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Culture Media ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Protein Levels ◽  
Renal Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Renal Tubular

Mesenchymal stem cells (MSCs) have been shown to be a promising therapy for many different diseases. Stem cell conditioned culture media (SCM) exhibit similar beneficial effects as MSCs. Albuminuria-induced epithelial-mesenchymal transition (EMT) plays an important role in progressive renal tubulointerstitial fibrosis in chronic renal disease. The present study tested the hypothesis that SCM inhibit albumin-induced EMT in cultured renal tubular cells. SCM were obtained by culturing rat adult MSCs for 3 days. Cultured renal proximal tubular cells were incubated with rat albumin (20μg/ml) and treated with SCM or control culture media. Our results showed that 48 h albumin incubation stimulated EMT in renal proximal tubular cells as shown by significant decrease in the protein levels of epithelial marker E-cadherin from 2.30 ± 0.27 to 0.87 ± 0.11 ( P < 0.05) and increase in the protein levels of mesenchymal marker fibroblast-specific protein 1 (FSP-1) (2.18±0.33 folds, P < 0.05). SCM treatment significantly inhibited these albumin-induced changes in E-cadherin and FSP-1 by 2.33±0.17 and 1.95±0.23 folds ( P < 0.05), respectively. Meanwhile, albumin increased the mRNA levels of pro-inflammatory factor monocyte chemoattractant protein-1 (MCP)-1 by nearly 30 folds compared with control. SCM almost abolished the increase of MCP-1 induced by albumin. Furthermore, Western blot results displayed that albumin rapidly decreased the cytosolic levels and increased the nuclear levels of NF-κB, indicating a translocation of NF-κB; immunofluorescence microscopy also demonstrated that albumin induced NF-κB translocation from the cytosol into nucleus. SCM blocked the translocation of NF-κB into nucleus. These results suggest that SCM attenuated albumin-induced EMT in renal tubular cells via inhibiting NF-κB activation and inflammation, which may serve as a new therapeutic approach for chronic kidney diseases. (Supported by NIH grant HL89563 and HL106042)

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