Maleate-induced bicarbonaturia in the dog: a carbonic anhydrase-independene effect

1976 ◽  
Vol 231 (4) ◽  
pp. 1010-1017 ◽  
Author(s):  
A Gougoux ◽  
G Lemieux ◽  
N Lavoie
Keyword(s):  
Carbonic Anhydrase ◽  
Intravenous Administration ◽  
Maleic Acid ◽  
Krebs Cycle ◽  
Urinary Ph ◽  
Renal Effects ◽  
Carbonic Anhydrase Inhibition ◽  
Tubular Lumen ◽  
Proximal Tubular ◽  
Anesthetized Dogs

Studies were performed to characterize the renal effects of maleate in anesthetized dogs. Following the intravenous administration of maleate or maleic acid (50 mg/kg), mean fractional bicarbonate excretion (CHCO3/GFR) rose to as high as 26%. Na, K, and phosphate excretion also increased markedly, whereas C1 excretion remained low. An initial transient fall in urinary pH from 6.53 to 6.13 contrasted sharply with the rapid alkalinization of the urine induced by acetazolamide administration. During saline expansion CHCO3/GFR rose from 4 to 37% after maleate administration, whereas Cl excretion did not change significantly. During continuous carbonic anhydrase inhibition with acetazolamide, maleate administration resulted in a further rise in CHCO3/GFR from 22 to 35%. Whereas CPO4/GFR increased only from 1 to 3% during acetazolamide administration, this ratio reached 75% following the addition of maleate. Fumarate, the transisomer of maleate, and malonate, a well-known inhibitor of Krebs cycle, failed to affect bicarbonate excretion. This study demonstrates that maleate inhibits the fraction of bicarbonate reabsorption uncatalyzed by carbonic anhydrase. Impaired anionic reabsorption of bicarbonate or accelerated passive backflux of this ion into proximal tubular lumen are the two mechanisms that best explain the bicarbonaturia induced by maleate.

Effect of carbonic anhydrase inhibition on proximal tubular bicarbonate reabsorption

1963 ◽  
Vol 205 (4) ◽  
pp. 693-696 ◽  
Author(s):  
James R. Clapp ◽  
John F. Watson ◽  
Robert W. Berliner
Keyword(s):  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Intravenous Administration ◽  
Distal Portion ◽  
Bicarbonate Concentration ◽  
Plasma Bicarbonate ◽  
Bicarbonate Reabsorption ◽  
Carbonic Anhydrase Inhibition ◽  
Before And After ◽  
Proximal Tubular

Samples of fluid from the proximal tubule were collected for the measurement of pH and bicarbonate concentration before and after the administration of acetazolamide (Diamox). Samples collected before acetazolamide were consistently more acid than plasma with the most acid samples coming from the more distal portion of the proximal tubule. After the intravenous administration of acetazolamide, the pH and bicarbonate concentration were consistently higher than in plasma. Bicarbonate concentrations as high as 2.8 times that in plasma were observed. The rise in proximal tubular fluid bicarbonate concentration after acetazolamide is presumably due to a reduction in the rate of bicarbonate reabsorption out of proportion to any impairment in proximal tubular fluid volume reduction.

Effect of carbonic anhydrase inhibition on mixed venous CO2 tension in anesthetized dogs

1960 ◽  
Vol 15 (3) ◽  
pp. 390-392 ◽  
Author(s):  
Stephen M. Cain ◽  
Arthur B. Otis
Keyword(s):  
Carbonic Anhydrase ◽  
Venous Blood ◽  
Carbonic Anhydrase Inhibitor ◽  
Mixed Venous Blood ◽  
Bicarbonate Concentration ◽  
Significant Difference ◽  
Carbonic Anhydrase Inhibition ◽  
Anesthetized Dogs ◽  
The Difference ◽  
Mixed Venous

The ventilation of one lung in dogs was isolated and that lung continually rebreathed into a small rubber bag. The Pco2 of a sample of the gas in the rebreathing bag was compared with the Pco2 calculated from pH and bicarbonate concentration determined in a sample of mixed venous blood drawn simultaneously. Before the injection of a carbonic anhydrase inhibitor, acetazolamide, the difference between the two values for Pco2 was not significant. After acetazolamide, a highly significant difference (P < 0.001) was found. Apparently, when carbonic anhydrase was inhibited, the dissolved CO2 of mixed venous blood did not attain equilibrium with bicarbonate by the time the blood entered the lung. Submitted on December 18, 1959

Additive effects of acetazolamide and fat emulsion on alveolar-arterial Pco2 difference

1962 ◽  
Vol 17 (4) ◽  
pp. 622-624 ◽  
Author(s):  
Stephen M. Cain
Keyword(s):  
Carbonic Anhydrase ◽  
Intravenous Infusion ◽  
Control Period ◽  
Additive Effects ◽  
Fat Emulsion ◽  
Arterial Pco2 ◽  
Intravenous Injections ◽  
Carbonic Anhydrase Inhibition ◽  
Additive Increase ◽  
Anesthetized Dogs

Alveolar and arterial gas tensions were measured in anesthetized dogs during a control period, after intravenous injections of a carbonic anhydrase inhibitor, and after rapid intravenous infusion of fat emulsion. These were carried out in sequence. The alveolar-arterial (A-a) Pco2 difference increased from about 6 mm Hg during the control to 26 mm Hg after carbonic anhydrase inhibition. A further increase took place after fat emulsion when the A-a Pco2 difference averaged 35 mm Hg. There was no increase in the A-a Po2 difference between carbonic anhydrase inhibition and fat emulsion. The additive increase in the A-a Pco2 difference strongly suggested that fat emulsion did not further interfere with the interconversion of CO2 and bicarbonate. Submitted on February 8, 1962

Coumaronochromone as antibacterial and carbonic anhydrase inhibitors from Aerva persica (Burm.f.) Merr.: experimental and first-principles approaches

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Muhammad Imran ◽  
Ahmad Irfan ◽  
Mohammed A. Assiri ◽  
Sajjad H. Sumrra ◽  
Muhammad Saleem ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
First Principles ◽  
Molecular Electrostatic Potential ◽  
Chemical Constituents ◽  
Bacterial Strains ◽  
Hirshfeld Analysis ◽  
Carbonic Anhydrase Inhibition ◽  
Inhibition Studies ◽  
Lowest Unoccupied Molecular Orbitals

AbstractThe Aerva plants are exceptionally rich in phytochemicals and possess therapeutics potential. Phytochemical screening shows that Aerva persica (Burm.f.) Merr. contains highest contents i.e., total phenolics, flavonoids, flavonols, tannins, alkaloids, carbohydrates, anthraquinones and glycosides. In-vitro antibacterial and enzymatic (carbonic anhydrase) inhibition studies on methanol extracts of A. persica indicated the presence of biological active constituents within chloroform soluble portions. Investigation in the pure constituents on the chloroform portions of A. persica accomplished by column chromatography, NMR and MS analysis. The bioguided isolation yields four chemical constituents of coumaronochromone family, namely aervin (1-4). These pure chemical entities (1-4) showed significant antibacterial activity in the range of 60.05–79.21 µg/ml against various bacterial strains using ampicillin and ciprofloxacin as standard drugs. The compounds 1-4 showed promising carbonic anhydrase inhibition with IC50 values of 19.01, 18.24, 18.65 and 12.92 µM, respectively, using standard inhibitor acetazolamide. First-principles calculations revealed comprehensive intramolecular charge transfer in the studied compounds 1-4. The spatial distribution of highest occupied and lowest unoccupied molecular orbitals, ionization potential, molecular electrostatic potential and Hirshfeld analysis revealed that these coumaronochromone compounds would be proficient biological active compounds. These pure constituents may be used as a new pharmacophore to treat leaukomia, epilepsy, glaucoma and cystic fibrosis.

scholarly journals Protective effects of carbonic anhydrase inhibition in brain ischaemia in vitro and in vivo models

2021 ◽  
Vol 36 (1) ◽  
pp. 964-976
Author(s):  
Ilaria Dettori ◽  
Irene Fusco ◽  
Irene Bulli ◽  
Lisa Gaviano ◽  
Elisabetta Coppi ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Protective Effects ◽  
Brain Ischaemia ◽  
In Vivo Models ◽  
Carbonic Anhydrase Inhibition

scholarly journals Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

2021 ◽  
Vol 36 (1) ◽  
pp. 1230-1235
Author(s):  
Secil Deniz ◽  
Tugba Kevser Uysal ◽  
Clemente Capasso ◽  
Claudiu T. Supuran ◽  
Ozen Ozensoy Guler
Keyword(s):  
Carbonic Anhydrase ◽  
Complementary Therapy ◽  
Carbonic Anhydrase Inhibition

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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