scholarly journals Jianpi Qushi Heluo Formula alleviates renal damages in Passive Hemann nephritis in rats by upregulating Parkin-mediated mitochondrial autophagy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin-hui Wang ◽  
Rui Lang ◽  
Qin Zeng ◽  
Ying Liang ◽  
Nan Chen ◽  
...  
Keyword(s):  
Renal Damage ◽  
Positive Control ◽  
Tubular Damage ◽  
Model Group ◽  
Active Components ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription ◽  
Experimental Rat Model ◽  
Complex Deposition ◽  
Renal Tubular

AbstractJianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.

scholarly journals Jianpi Qushi Heluo Formula Alleviates Renal Damages in Passive Hemann Nephritis Rats by Upregulating Parkin-Mediated Mitochondrial Autophagy

2021 ◽  
Author(s):  
Xin-hui Wang ◽  
Rui Lang ◽  
Qin Zeng ◽  
Nan Chen ◽  
Zhi-zhong Ma ◽  
...  
Keyword(s):  
Positive Control ◽  
Control Group ◽  
Tubular Damage ◽  
Model Group ◽  
Active Components ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription ◽  
Experimental Rat Model ◽  
Complex Deposition ◽  
Renal Tubular

Abstract Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating membranous nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine(TET), and Benazepril was used as a positive control group. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 hour urinary protein, total cholesterol (TC) and increased serum albumin (ALB). Histology showed that JQHF significant improvements of glomerular hyperplasia, renal tubular damage, IgG immune complex deposition and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF decreasing the level of Reactive Oxygen Species and apoptosis rate, upregulating the level of mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of Parkin and LC3II, and downregulating the expression of Cytochrome c and Cleaved caspase-3 in the kidneys of MN rats. Similarly, TET treatment significantly upregulates the mitochondrial autophagy and decrease the apoptosis of rats after 4 weeks compared with the Model group. Notably, combined with the above results, the ability to alleviates renal damages of JQHF was significantly better than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by Parkin pathways.

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.

Immunomodulating Effects of Fractioned Polysaccharides Isolated from Yu-Ping-Feng-Powder in Cyclophosphamide-Treated Mice

2006 ◽  
Vol 34 (04) ◽  
pp. 631-641 ◽  
Author(s):  
Xiang-Tao Chen ◽  
Jun Li ◽  
Hui-Li Wang ◽  
Wen-Ming Cheng ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Probability ◽  
Delayed Type Hypersensitivity ◽  
T Cell Proliferation ◽  
Splenocyte Proliferation ◽  
Active Components ◽  
Humoral And Cellular Immunity ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription ◽  
Ifn Γ

Yu-Ping-Feng-Powder (YP), a traditional Chinese medicine prescription, is widely applied in China for the cure and prevention of diseases related to immunodeficiency. To test whether the fractioned polysaccharides (YPF-P) isolated from YP have immunomodulating activities, the effects of YPF-P on cyclophosphamide (Cy)-treated mice were studied in relation to phagocytosis of macrophage, splenocyte proliferation, and humoral, and cellular immunity parameters. It was found that YPF-P enhances phagocytic activity, augments ConA- or LPS-stimulated T cell proliferation, increases the quantitative haemolysis of SRBC (QHS) and delayed-type hypersensitivity reaction (DTH) to dinitrofluorobenzene. Hence, YPF-P restored the immuno-competence suppressed by Cy. YPF-P also augmented IL-2 and IFN-γ production, but failed to increase IL-4 production, which indicates that there is high probability that it enhance Th1 function. These results suggested that YPF-P has immunomodulating effects and that the polysaccharides constitute one of the active components of YP.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients

2020 ◽  
Vol 49 (5) ◽  
pp. 560-566 ◽  
Author(s):  
Keren-Lee Rozenfeld ◽  
David Zahler ◽  
Moshe Shtark ◽  
Ilana Goldiner ◽  
Gad Keren ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Renal Damage ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Tubular Damage ◽  
Renal Tubular Damage ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Renal Tubular ◽  
Neutrophil Gelatinase

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among ­ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(–) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(–) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. Results: Of the study patients, 56 (42%) were NGAL(–)/sCr(–), 58 (44%) NGAL(+)/sCr(–), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(–) patients developed the composite endpoint when compared to NGAL(–)/sCr(–) patients (64 vs. 46%; OR 2.1, [95% CI 1.1–4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. Conclusions: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

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.

scholarly journals Fatal diquat intoxication

2009 ◽  
Vol 66 (6) ◽  
pp. 477-481 ◽  
Author(s):  
Jasmina Jovic-Stosic ◽  
Gordana Babic ◽  
Veljko Todorovic
Keyword(s):  
Renal Damage ◽  
Medical Literature ◽  
Brain Infarction ◽  
Healthy Woman ◽  
Tubular Damage ◽  
Acute Renal Injury ◽  
Mucosal Surfaces ◽  
Pontine Hemorrhage ◽  
Severe Gastroenteritis ◽  
Renal Tubular

Background. Since the introduction of diquat in agriculture practice in 1960's, about 40 cases of poisoning have been described in detail in medical literature. Case report. We presented two cases. A case one, a 35-year-old, previously healthy, woman ingested 14% diquat solution. The poisoning had fulminant course, consisted of severe stomachache, vomiting, cardiocirculatory shock, respiratory failure and cardiac arrest 20 hours post-ingestion. Autopsy revealed myocardial infarction, bronchopneumonia and incipient renal damage. A case two, a 64-year-old man developed severe gastroenteritis, corrosive lesions of mucosal surfaces, acute renal injury, arrhythmias, brain stem infarction and bronchopneumonia. The diagnosis of diquat poisoning was made retrospectively upon the clinical picture and identification of pesticides he had been exposed to. The patient died 18 days post-exposure. The most prominent findings on autopsy were pontine hemorrhage and infarction, bronchopneumonia, left ventricle papillary muscle infarction and renal tubular damage. Conclusion. Cardiocirculatory disturbances led to fatal complications, the heart and brain infarction. We pointed out the heart as one of the most severely affected organs in diquat poisoning.

scholarly journals AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Critical Role ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubular Cell ◽  
Ang Ii ◽  
Renal Tubular

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.

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.

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