Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The toxic effects of imidocarb diproprionate (3,3'-bis [2 imidazolin-2yl]-carbanilde diproprionate) were evaluated in adult goats given (intramuscular injection) a lethal dose (6.75 mg/kg). The immediate clinical signs of toxicosis were transient excessive salivation and diarrhea. Anorexia, dyspnea, recumbency, and death occurred between postinjection days (PID) 4 and 8, during which time 7 goats died and 4 moribund goats were euthanatized. There were marked increases in mean serum urea nitrogen concentration and significant increases in serum glutamic oxalacetic transminase activity and in the mean number of circulating neutrophils after PID 4. Renal hyperemia and enlargement were evident by PID1. Serosanguineous fluid in the trachea and major bronchi, pulmonary congestion and edema, hydrothorax, hydroperitoneum, and less frequently hydropericardium were observed on and after day 4. Microscopic renal tubular lesions rapidly progressed from pyknotic epithelial nuclei observed at 6 and 12 hours to acute tubular necrosis of epithelium of the proximal convoluted tubules on days 1 and 2. Pulmonary congestion and edema; hemorrhage into alveoli, bronchioles, and bronchi; and intracytoplasmic lipid vacuoles within the hepatocytes in the periacinar zones of the hepatic lobules were observed on or after day 4. Succinic dehydrogenase and adenosine triphosphatase activities decreased progressively in the epithelial cells of the proximal convoluted tubules. The decreases in cellular enzymatic activity occurred shortly after the appearance of microscopic lesions in the tubular epithelium.
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PMID:Clinical, histologic, and histochemical study of imidocarb diproprionate toxicosis in goats. 13 83

To further characterize changes in tubular Na-K-ATPase in acute tubular necrosis (ATN), segmental analysis was performed in rat nephrons. Na-K-ATPase was assayed in the following segments: proximal convolution (PC), proximal straight (PS), outer medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convolution (DC) and cortical collecting duct (CCD) in three groups of rats: 1.) intact; 2.) moderate non-oliguric ATN; and 3.) severe oliguric ATN. GFR and CNa/GFR X 100 were in group 1 0.80 +/- 0.05 ml/min and 0.68 +/- 0.06, in group 2 0.14 +/- 0.02 and 1.46 +/- 0.35, and in group 3 0.04 +/- 0.01 and 0.46 +/- 0.15, respectively. Na-K-ATPase in PC and PS were similar in all three groups. Na-K-ATPase levels were in MTAL: in group 1 37 +/- 2 X 10(-11) mol/mm/min, in group 2 20 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 24 +/- 2 X 10(-11), P less than 0.001 versus group 1. In CTAL Na-K-ATPase levels were: in group 1 40 +/- 2 X 10(-11), in group 2 33 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 27 +/- 2 X 10(-11), P less than 0.001 versus groups 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced Na-K-ATPase in distal nephron in glycerol-induced acute tubular necrosis. 215 4

Sprague-Dawley rats given gentamicin from 10 to 70 mg/kg/day for 9 days showed a linear decrease in glomerular filtration rate with increasing dose, paralleled by histologic changes of acute tubular necrosis and cast formation only at the higher doses. Nephrotoxicity was correlated with the peak, rather than trough, serum gentamicin levels in this study, suggesting that it is the mean level of gentamicin over time that determines renal injury. The polyuria caused by gentamicin resulted mainly from a tubular concentrating defect rather than enhanced sodium or osmolal excretion and may be explained by the finding of a predominance of casts in the medullary thin limbs of the loops of Henle. No effect of gentamicin on the activity of cortical or medullary sodium-potassium adenosine triphosphatase was found to account for the modest sodium wasting. Concurrent administration of sodium cephalothin decreased the renal toxicity of gentamicin at high doses, an effect not explained by the added sodium or nonreabsorbable anion.
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PMID:Features of gentamicin nephrotoxicity and effect of concurrent cephalothin in the rat. 687 60

The present study was designed to determine whether the administration of free radical scavengers, superoxide dismutase (SOD), catalase or dimethylsulfoxide (DMSO) is able to ameliorate ischemia/reperfusion injury in the canine kidney and also ascertain whether or not a relationship exists between oxygen free radicals and membrane-bound Na(+)-K(+)-ATPase activity. In 23 dogs, the vascular pedicle of the left kidney was clamped for 75 min at room temperature. The experimental animals received free radical scavengers for 30 min starting at 2 min prior to reperfusion. Renal tissue specimens were enzyme-histochemically examined regarding the activity of membrane-bound Na(+)-K(+)-ATPase, and a marked reduction just before reperfusion was revealed. The SOD- and the DMSO-treated groups showed a marked recovery of the membrane-bound Na(+)-K(+)-ATPase activity; however, the untreated and the catalase-treated groups still demonstrated a marked reduction 1 day after reperfusion. At the same time, widespread acute tubular necrosis in the cortex was observed in the untreated and catalase groups in comparison with the SOD and the DMSO groups. In addition, the SOD and the DMSO groups significantly preserved better renal function. Based on these findings, it was thus concluded that free radical scavengers ameliorate the recovery of depressed membrane-bound Na(+)-K(+)-ATPase activity and ischemia/reperfusion injury in the canine kidney.
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PMID:The influence of oxygen free radical scavengers on the reduction of membrane-bound Na(+)-K(+)-ATPase activity induced by ischemia/reperfusion injury in the canine kidney. 873 Apr 34

Tubulointerstitial nephritis is a common clinicopathological finding in leptospirosis. Clinically, nonoliguric acute kidney injury (AKI), hypokalemia, sodium, and magnesium wasting frequently occur in leptospirosis. The exact mechanisms of renal involvement remain largely unclear. Immunohistochemistry to detect expression of the endogenous sodium/hydrogen exchanger isoform 3 (NHE 3), aquaporin 1 and 2, alpha-Na(+)K(+)ATPase, and sodium-potassium-chloride cotransporter in its NKCC2 isoform was performed on kidneys removed during autopsy of human leptospirosis cases and kidneys removed during autopsy of human non-leptospirosis cases with and without evidence of acute tubular necrosis (ATN). A decrease in NHE 3, aquaporin 1, and alpha-Na(+)K(+)ATPase expression occurred in proximal convoluted tubule cells. Expression of aquaporin 1 was preserved along the descending thin limb of the loop of Henle in the outer medulla. alpha-Na(+)K(+)ATpase expression was essentially preserved in the distal tubules, i.e., the thick ascending limb of the loop of Henle, macula densa, and distal convoluted tubule. Aquaporin 2 expression in the collecting tubules was enhanced compared to those of non-leptospirotic kidneys. NKCC2 cotransport isoform was expressed in the thick ascending limb of the loop of Henle and was essentially preserved in leptospirotic kidneys. Primary injury of the proximal convoluted tubules is regarded as the hallmark of the kidney in leptospirosis. Sodium and water transport are particularly affected with increased distal potassium excretion, hypokalemia, and polyuria. Enhanced expression of aquaporin 2 in medullary collecting tubules is probably an attempt to retain water during the nonoliguric phase of renal failure.
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PMID:Acute kidney injury in human leptospirosis: an immunohistochemical study with pathophysiological correlation. 2021 29

Contrast media induce various factors that may increase vasoconstriction and decrease vasodilatation in the renal medulla, leading to hypoxia and acute tubular necrosis known as contrast-induced nephropathy (CIN) that tends to occur in diabetics and patients with preexisting renal insufficiency. Contrast media inhibit mitochondrial enzyme activities and subsequently increase adenosine through hydrolysis of ATP. Both catabolism of adenosine and medullary hypoxia generate reactive oxygen species (ROS) that scavenge nitric oxide (NO). Released along with endothelin and prostaglandin from endothelial cells exposed to contrast media, adenosine activates the A1 receptor that mainly constricts afferent arteriole at the glomerulus but not the medullary vasculature. Adenosine also activates the A2 receptor that increases NO production, leading to medullary vasodilatation which is induced by activation of endothelin-B receptor and G-protein coupled E-prostanoid receptor 2, and 4 of prostaglandin PGE2 respectively as well. Conversely medullary vasoconstriction is mediated by activating endothelin-A receptor and G-protein coupled E-prostanoid receptor 1, and 3 of prostaglandin PGE2 respectively. The osmotic load of contrast media increases interstitial pressure and sodium transport and thus oxygen consumption. Risking hypoxia, increased medullary oxygen consumption may also result from stimulating Na(+)-K(+)-ATPase activity by endothelin-A receptor. N-acetylcysteine (NAC) scavenges ROS and therefore preserves NO that not only dilates medullary vasculature but also reduces sodium reabsorption and oxygen consumption, tipping the balance against medullary vasoconstriction, hypoxia, and thus CIN. While prostacyclin and its analog, iloprost, prevent CIN by inducing medullary vasodilatation, atrial natriuretic peptide (ANP) may do so by inhibiting renin secretion.
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PMID:Pathophysiology of contrast-induced nephropathy. 2302 89