The Kidney

Bioprinting ◽  
2021 ◽  
pp. 183-201
Author(s):  
Kenneth Douglas
Keyword(s):  
Fluorescence Microscopy ◽  
Serum Albumin ◽  
Blood Vessels ◽  
Kidney Tissue ◽  
Proximal Convoluted Tubule ◽  
Proximal Tubules ◽  
Drug Induced ◽  
Series Of Experiments ◽  
Critical Components ◽  
Vectorial Transport

Abstract: This chapter puts forward a series of experiments in which scientists bioprinted one of the critical components of a kidney’s nephron (the filtering unit of the kidney), namely the proximal convoluted tubule where the majority of nutrient absorption back into the bloodstream takes place (and where most drug-induced toxicities of the kidney occur). The same team of researchers bioprinted colocalized (printed very close together) proximal tubules and blood vessels and, with the use of fluorescence microscopy, were able to observe vectorial transport, the process in which valuable nutrients such as serum albumin are selectively reabsorbed into the bloodstream. They also induced a state of hyperglycemia and administered a countermeasure drug, thus demonstrating the ability of their bioprinted kidney tissue to functionally respond as native kidney tissue does to an overdose of glucose and to a drug designed to mitigate this undesirable condition.

scholarly journals Antioxidant Activity, Phenolic Profile, and Nephroprotective Potential of Anastatica hierochuntica Ethanolic and Aqueous Extracts against CCl4-Induced Nephrotoxicity in Rats

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2973
Author(s):  
Tariq I. Almundarij ◽  
Yousef M. Alharbi ◽  
Hassan A. Abdel-Rahman ◽  
Hassan Barakat
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Therapeutic Agent ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Total Phenolic ◽  
Drug Induced ◽  
Total Carotenoids ◽  
Phenolic Profile ◽  
Better Than

Kaff-e-Maryam (Anastatica hierochuntica L.) is extensively used to treat a range of health problems, most notably to ease childbirth and alleviate reproductive system-related disorders. This study aimed to evaluate the effect of A. hierochuntica ethanolic (KEE), and aqueous (KAE) extracts on CCl4-induced oxidative stress and nephrotoxicity in rats using the biochemical markers for renal functions and antioxidant status as well as histopathological examinations of kidney tissue. A. hierochuntica contained 67.49 mg GAE g−1 of total phenolic compounds (TPC), 3.51 µg g−1 of total carotenoids (TC), and 49.78 and 17.45 mg QE g−1 of total flavonoids (TF) and total flavonols (TFL), respectively. It resulted in 128.71 µmol of TE g−1 of DPPH-RSA and 141.92 µmol of TE g−1 of ABTS-RSA. A. hierochuntica presented superior antioxidant activity by inhibiting linoleic acid radicals and chelating oxidation metals. The HPLC analysis resulted in 9 and 21 phenolic acids and 6 and 2 flavonoids in KEE and KAE with a predominance of sinapic and syringic acids, respectively. Intramuscular injection of vit. E + Se and oral administration of KEE, KAE, and KEE + KAE at 250 mg kg−1 body weight significantly restored serum creatinine, urea, K, total protein, and albumin levels. Additionally, they reduced malondialdehyde (MOD), restored reduced-glutathione (GSH), and enhanced superoxide dismutase (SOD) levels. KEE, KAE, and KEE + KAE protected the kidneys from CCl4-nephrotoxicity as they mainly attenuated induced oxidative stress. Total nephroprotection was about 83.27%, 97.62%, and 78.85% for KEE, KAE, and KEE + KAE, respectively. Both vit. E + Se and A. hierochuntica extracts attenuated the histopathological alteration in CCl4-treated rats. In conclusion, A. hierochuntica, especially KAE, has the potential capability to restore oxidative stability and improve kidney function after CCl4 acute kidney injury better than KEE. Therefore, A. hierochuntica has the potential to be a useful therapeutic agent in the treatment of drug-induced nephrotoxicity.

Megalin/gp330 mediates uptake of albumin in renal proximal tubule

1996 ◽  
Vol 271 (4) ◽  
pp. F900-F907 ◽  
Author(s):  
S. Cui ◽  
P. J. Verroust ◽  
S. K. Moestrup ◽  
E. I. Christensen
Keyword(s):  
Bovine Serum Albumin ◽  
Ligand Binding ◽  
Serum Albumin ◽  
Proximal Tubule ◽  
Proximal Tubules ◽  
Rat Serum ◽  
Gold Particles ◽  
Receptor Associated Protein ◽  
Rat Serum Albumin

Serum albumin filtered in renal glomeruli is reabsorbed very efficiently in the proximal tubule by endocytosis. The present study was undertaken to determine whether megalin/gp330 binds and mediates endocytosis of albumin. Rat serum albumin (RSA) labeled with 125I and colloidal gold particles labeled with bovine serum albumin (BSA) were microinfused into rat surface proximal tubules in vivo, and tubular uptake was determined in the presence or absence of different substances known to interfere with ligand binding to megalin. Binding of 125I-BSA and 125I-RSA to purified megalin was also determined directly using Sepharose columns. The results revealed that the tubular uptake of 125I-labeled RSA was significantly inhibited by receptor-associated protein (RAP), which reduced the uptake by > 50% and by cold RSA. The uptake of BSA gold by the proximal tubule was very intensive. BSA gold was found in small and large endocytic vacuoles, dense apical tubules, and in lysosomes. The uptake was reduced by RAP to 17%, by EDTA to 19%, by BSA to 16%, by megalin to 35%, by cytochrome c to 49%, and, together with gentamicin, there was virtually no uptake. Megalin-Sepharose columns bound 125I-labeled BSA as well as 125I-RSA, the binding was inhibited by RAP and EDTA, and analysis of the eluate revealed the bound tracer to be albumin. In conclusion, the present study demonstrates that megalin is a mediator of albumin reabsorption in renal proximal tubules.

scholarly journals Immunopathogenesis of Acute Kidney Injury

2018 ◽  
Vol 46 (8) ◽  
pp. 930-943 ◽  
Author(s):  
Zaher A. Radi
Keyword(s):  
Acute Kidney Injury ◽  
T Cells ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Drug Induced ◽  
Inflammatory Damage ◽  
Anti Inflammatory ◽  
Renal Tubular ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Pathophysiologically, the classification of acute kidney injury (AKI) can be divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal. Emerging evidence supports the involvement of renal tubular epithelial cells and the innate and adaptive arms of the immune system in the pathogenesis of intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen-associated molecular patterns, hypoxia inducible factors, toll-like receptors, complement system, oxidative stress, adhesion molecules, cell death, resident renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural killer T cells, cytokines, and secreted chemokines contribute to the immunopathogenesis of AKI. However, other immune cells and pathways such as M2 macrophages, regulatory T cells, progranulin, and autophagy exhibit anti-inflammatory properties and facilitate kidney tissue repair after AKI. Thus, therapies for AKI include agents such as anti-inflammatory (e.g., recombinant alkaline phosphatase), antioxidants (iron chelators), and apoptosis inhibitors. In preclinical toxicity studies, drug-induced kidney injury can be seen after exposure to a nephrotoxicant test article due to immune mechanisms and dysregulation of innate, and/or adaptive cellular immunity. The focus of this review will be on intrinsic AKI, as it relates to the immune and renal systems cross talks focusing on the cellular and pathophysiologic mechanisms of AKI.

Rapid modulation of Na+/K+-ATPase activity in osmoregulatory tissues of a salmonid fish

2001 ◽  
Vol 204 (4) ◽  
pp. 701-709 ◽  
Author(s):  
C.K. Tipsmark ◽  
S.S. Madsen
Keyword(s):  
Cyclic Amp ◽  
Atpase Activity ◽  
Salmo Trutta ◽  
Kidney Tissue ◽  
Gill Tissue ◽  
Phosphatase Inhibitors ◽  
Protein Phosphatase Inhibitors ◽  
Brown Trout Salmo Trutta ◽  
Series Of Experiments ◽  
Rapid Modulation

The effects of cyclic AMP on Na+/K+-ATPase activity were studied in the gill and kidney of the euryhaline brown trout Salmo trutta using two different experimental approaches. In the first series of experiments, in situ Na+/K+-ATPase activity was analyzed by measuring the ouabain-sensitive uptake of non-radioactive rubidium (Rb+) into gill cells and blocks of gill and kidney tissue. Rubidium uptake was linear for at least 30 min and was significantly inhibited by 1 mmol × l(−1) ouabain. Several agents presumed to increase the intracellular cyclic AMP concentration inhibited ouabain-sensitive Rb+ uptake in both gill (0.5 and 2 mmol × l(−1) dibutyryl-cyclic AMP, 1 mmol × l(−1) theophylline, 10 micromol × l(−1) forskolin and 10 micromol × l(−1)isoproterenol) and kidney (10 micromol × l(−1) forskolin) tissue from freshwater-acclimated fish. In a separate series of experiments, ATP hydrolase activity was assayed in a permeabilised gill membrane preparation after incubation of tissue blocks with 10 micromol × l(−1)forskolin. Forskolin elevated gill cyclic AMP levels 40-fold, inhibited maximal enzymatic Na+/K+-ATPase activity (Vmax) in gill tissue from both freshwater- and seawater-acclimated fish and reduced the apparent K+ affinity in the gills of seawater-acclimated fish, demonstrating that the effects are mediated through modifications of the enzyme itself. The protein phosphatase inhibitors okadaic acid and cyclosporin A did not affect forskolin-induced inhibition of Na+/K+-ATPase activity, indicating that forskolin-mediated modulation was stable for the duration of assay. We suggest that cyclic-AMP-mediated phosphorylation through protein kinases may underlie the rapid modulation of Na+/K+-ATPase activity in the osmoregulatory tissues of euryhaline teleosts.

Prevalence and Risk Factors Associated with First-Line Anti-Tuberculosis Induced Hepatotoxicity in Suratthani Hospital, Thailand

2021 ◽  
Vol 104 (2) ◽  
pp. 233-239
Keyword(s):  
Risk Factors ◽  
Serum Albumin ◽  
Clinical Symptoms ◽  
Significant Risk ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
First Line ◽  
Drug Induced ◽  
Factors Associated ◽  
Drug Risk

ackground: Tuberculosis (TB) is a major public health problem, including Thailand. Anti-TB drugs are very effective treatment, but they can cause hepatotoxicity. Data on the prevalence of anti-TB drug-induced hepatotoxicity (DIH), as well as the contributing risk factors, are scarce in Thailand. Objective: To measure the prevalence and identify risk factors associated with first-line drugs (FLD) induced hepatoxicity in TB patients. Materials and Methods: The present study was a retrospective study design in TB clinic of Suratthani Hospital, in Southern Thailand. All patients diagnosed with TB and received FLD between January and December 2017, were eligible for the study. Hepatoxicity defined as the following criteria: serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >5x upper limit of normal (ULN) without symptoms, or AST or ALT >3x ULN with clinical symptoms. Results: Of all the 198 TB cases, 18 were identified as DIH. Prevalence of DIH was 9.1%. Hepatitis after FLD was independently associated with age>60 years (adjusted OR [aOR] 28.49, 95% CI 2.68 to 302.95, p=0.005) and serum albumin <3.5 g/dL (aOR 20.97, 95% CI 2.11 to 208.51, p=0.009). Conclusion: Age of more than 60 years and low serum albumin of less than 3.5 g/dL were significant risk factors associated with first-line anti-TB drugs induced hepatoxicity. Keywords: Hepatoxicity, Anti-tuberculosis drug, Risk factor, Thailand

scholarly journals Sodium valproate inhibits the movement of secretory vesicles in rat hepatocytes

1988 ◽  
Vol 249 (2) ◽  
pp. 513-519 ◽  
Author(s):  
M E Bellringer ◽  
K Rahman ◽  
R Coleman
Keyword(s):  
Serum Albumin ◽  
Sodium Valproate ◽  
Rat Hepatocytes ◽  
Biliary Fistula ◽  
Rat Serum ◽  
Control Series ◽  
Anti Epileptic Drug ◽  
Series Of Experiments ◽  
Branched Chain ◽  
Rat Livers

Sodium valproate (VPA), a simple 8-carbon branched chain fatty acid, is an effective anti-epileptic drug with an occasional serious side effect of liver damage, including the accumulation of triacylglycerols within hepatocytes, and reductions in serum protein concentrations. By investigating the effects of VPA, using biliary fistula rats and isolated perfused rat livers, we have shown that secretion of triacylglycerols and rat serum albumin at the sinusoidal pole of hepatocytes, and of phospholipids, lysosomal contents, and IgA at their biliary pole, are all reduced, to somewhat different extents, by acute VPA administration. In addition, the vesicular transcytosis of exogenous protein (i.e. bovine serum albumin) from the perfusion fluid into bile is also decreased by VPA administration. To determine whether the phenomena were specific to VPA, a control series of experiments was also performed using octanoate (a straight-chain analogue of VPA). With the biliary fistula rats, octanoate did not show inhibition of secretion as compared with the saline controls; with the isolated perfused livers, however, octanoate did show such an inhibition. These phenomena suggest that VPA inhibition of secretion may be a factor in its hepatotoxicity, as the effects are apparent in both the whole animal and the isolated perfused liver, whereas octanoate is not hepatotoxic in the whole animal. Since when octanoate is administered to the isolated liver it causes an inhibition in secretion similar to that caused by VPA, it may be that the large dose of this compound reaching the liver affects a key step in liver metabolism or vesicle transport under these circumstances. Since octanoate does not normally reach the liver in such amounts, as it will normally be metabolized by other tissues, it is not hepatotoxic in the whole animal as is VPA.

scholarly journals Spontaneous and Drug-induced Arteritis/Polyarteritis in the Göttingen Minipig—Review

2018 ◽  
Vol 46 (2) ◽  
pp. 121-130 ◽  
Author(s):  
Zuhal Dincer ◽  
Virginie Piccicuto ◽  
Ursula Junker Walker ◽  
Andreas Mahl ◽  
Sean McKeag
Keyword(s):  
Spinal Cord ◽  
Urinary Bladder ◽  
Blood Vessels ◽  
Polyarteritis Nodosa ◽  
Pain Syndrome ◽  
Vascular Changes ◽  
Drug Induced ◽  
Göttingen Minipig ◽  
Age Related ◽  
Immune Mediated

Arteritis/polyarteritis occurs spontaneously in many species used in preclinical toxicology studies. In Göttingen minipigs, arteritis/polyarteritis is an occasionally observed background change. In the minipig, this finding differs in frequency and nature from age-related polyarteritis nodosa in rats or monkeys, and Beagle pain syndrome in dogs. In minipigs, it can be present in a single small- or medium-sized artery of an organ or a few organs and is most commonly recorded in the cardiac and extracardiac blood vessels, vagina, oviduct, rectum, epididymis, spinal cord, pancreas, urinary bladder, kidneys, and stomach. The etiology is unknown although it has been considered in minipigs as well as in rats, dogs, and monkeys to be possibly immune mediated. This background change is important with respect to its nature and distribution in the minipig in order to distinguish it from drug-induced vascular changes, which might occur in similar locations and have similar morphologic features. This review summarizes the morphology, incidence, and predilection sites of arteritis as a spontaneously occurring background change and as a drug-induced vasculopathy in the minipig, and also describes the main aspects to consider when evaluating vascular changes in Göttingen minipig toxicity studies and their human relevance.

scholarly journals Intracellular pH regulation in the renal proximal tubule of the salamander. Basolateral HCO3- transport.

1983 ◽  
Vol 81 (1) ◽  
pp. 53-94 ◽  
Author(s):  
W F Boron ◽  
E L Boulpaep
Keyword(s):  
Negative Charge ◽  
Ph Regulation ◽  
Basolateral Membrane ◽  
Proximal Tubules ◽  
Ambystoma Tigrinum ◽  
Intracellular Ph Regulation ◽  
Rapid Fall ◽  
Tight Linkage ◽  
Series Of Experiments ◽  
Basolateral Membrane Potential

We have used pH-, Na-, and Cl-sensitive microelectrodes to study basolateral HCO3- transport in isolated, perfused proximal tubules of the tiger salamander Ambystoma tigrinum. In one series of experiments, we lowered basolateral pH (pHb) from 7.5 to 6.8 by reducing [HCO3-]b from 10 to 2 mM at a constant pCO2. This reduction of pHb and [HCO3-]b causes a large (approximately 0.35), rapid fall in pHi as well as a transient depolarization of the basolateral membrane. Returning pHb and [HCO3-]b to normal has the opposite effects. Similar reductions of luminal pH (pHl) and [HCO3-]l have only minor effects. The reduction of [HCO3-]b and pHb also produces a reversible fall in aiNa. In a second series of experiments, we reduced [Na+]b at constant [HCO3-]b and pHb, and also observed a rapid fall in pHi and a transient basolateral depolarization. These changes are reversed by returning [Na+]b to normal. The effects of altering [Na+]l in the presence of HCO3-, or of altering [Na+]b in the nominal absence of HCO3-, are substantially less. Although the effects on pHi and basolateral membrane potential of altering either [HCO3-]b or [Na+]b are largely blocked by 4-acetamido-4-isothiocyanostilbene-2,2'-disulfonate (SITS), they are not affected by removal of Cl-, nor are there accompanying changes in aiCl consistent with a tight linkage between Cl- fluxes and those of Na+ and HCO3-. The aforementioned changes are apparently mediated by a single transport system, not involving Cl-. We conclude that HCO3- transport is restricted to the basolateral membrane, and that HCO3- fluxes are linked to those of Na+. The data are compatible with an electrogenic Na/HCO3 transporter that carries Na+, HCO3-, and net negative charge in the same direction.

Relationship between cytokeratins CK8/18&19 and KIM-1 level in urine with apoptosis and necrosis of nephrotheliocytes in rats with toxic nephropathy

2020 ◽  
Vol 20 (2) ◽  
pp. 17-26
Author(s):  
Konstantin V. Sivak ◽  
Ruslan G. Guseynov
Keyword(s):  
Cell Death ◽  
Fluorescence Microscopy ◽  
Urinary Excretion ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Uranyl Acetate ◽  
Tissue Polypeptide Antigen ◽  
Acetate Dihydrate ◽  
Apoptosis And Necrosis ◽  
The Relationship

The aim of the article. The aim of this work was to elucidate the role of apoptosis and necrosis in kidney tissue in the development of acute renal damage in poisoning rats with uranyl acetate. The research objectives included modeling acute poisoning in rats, collecting urine and kidney tissue with identifying markers of programmed cell death, tissue polypeptide antigen (TPA, fragments of cytokeratin CK8/18 19), and KIM-1 level in urine. An analysis of the relationship between an early increase in urinary excretion of the TPA and apoptosis level, a kidney injury molecule KIM-1, and necrosis of the tubular epithelial cells during rat poisoning with nephrotoxin uranyl acetate dihydrate. Materials and methods. Uranyl acetate dihydrate (CAS # 6159-44-0) was administered to 18-week old female Sprague-Dawley rats weighing 175199 g by intragastrically at a dose of 30 mg / 100 g body weight once through an atraumatic probe. Rats were divided into 2 groups: group 1 intact animals (12 individuals), group 2 animals with induced AKI (36 individuals). Daily urine was collected before, on the 1st, 3rd, and 7th day after poisoning in metabolic cages. The concentration of creatinine, KIM-1, tissue polypeptide antigen was measured in urine. In the kidney tissue samples, the fraction of dead cells and nephrothelial cells with apoptotic signs of nuclear changes by fluorescence microscopy with AMD Hoechst 33342 staining was determined. Data processing was performed using GraphPad Prism 6.0. Results. Acute kidney injury in rats with uranyl acetate dihydrate leads to a rapid increase in urinary excretion of cytokeratin fragments CK8/18 19 due to subtotal damage to nephrothelial cells due to activation of apoptosis, and then an increase in KIM-1 as a marker of necrotic cell death. Fluorescence microscopy of nuclear chromatin stained renal tubule cells showed a significant increase in the proportion of cells with apoptotic bodies, chromatin condensation, and a change in the shape of the nuclei. Conclusion. Examination of the curves of risk function showed that only creatinine in blood (p = 0.0002) and urine KIM-1 (p = 0.0005) had a significant level of association with rat mortality and necrosis of the nephrothelial cells. A comparative analysis of the relationship between apoptosis biomarker levels TPA (cytokeratin fragments CK8/18 19) and urinary nephrotoxicity marker KIM-1 with the proportion of kidney cells dying by the mechanism of necrosis and apoptosis revealed positive correlations of Spearman in pairs of cytokeratin CK8/18 19 apoptosis (r = 0.73, 95% CI 0.450.88, p 0.0001), KIM-1 necrosis (r = 0.98, 95% CI 0.960.99, p 0.0001). The revealed relationship indicated the possibility of determining urinary tissue polypeptide antigen TPA as a marker of the early stage of acute kidney damage as a surrogate marker of tubular cell apoptosis, and KIM-1 as a marker for necrosis of nephrothelial cells.

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