Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema states, to increase urine flow and flush out debris from the renal tubules in patients with acute tubular necrosis, and to increase toxin excretion in patients with barbiturate, salicylate or bromide intoxication. As an obligate extracellular solute it may be useful to ameliorate symptoms of the dialysis disequilibrium syndrome, to decrease cerebral edema following trauma or cerebrovascular accident, and to prevent cell swelling related to renal ischemia following cross-clamping of the aorta. Largely unexplored uses for mannitol include its use as an osmotic agent in place of dextrose in peritoneal dialysis solutions, its use to maintain urine output in patients newly begun on hemodialysis, and its use to limit infarct size following acute myocardial infarction.
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PMID:Mannitol. 38 67

An elevation in cytosolic free calcium (Cai) produced by cellular ATP depletion may contribute to the initiation of cytotoxic events in renal ischemia. To evaluate whether ATP depletion results in a rise in Cai we examined the effect of cyanide and 2-deoxy-D-glucose on the Cai of Madin-Darby canine kidney cells. Exposure to the metabolic inhibitors resulted in a rise in Cai from 112 +/- 11 to 649 +/- 99 nM in 15 min. This combination of metabolic inhibitors also resulted in a decrement of cell ATP to 11 +/- 2% of control by 15 min. Experiments that were performed with other metabolic inhibitors confirm that the increment in Cai is due to inhibition of ATP synthesis. With the removal of cyanide and 2-deoxy-D-glucose, Cai recovered to 101 +/- 16 nM. In the absence of extracellular calcium activity (Ca0), Cai declined from 127 +/- 7 to 38 +/- 6 nM, whereas with cyanide plus 2-deoxy-D-glucose in the absence of Ca0 the Cai rose from 108 +/- 21 to 151 +/- 28 nM. Because the rise in Cai produced by ATP depletion in the absence of Ca0 is significantly less than that which occurs in the presence of Ca0, influx of Ca0 is necessary for the maximal rise of Cai. The rise in Cai that occurred in the absence of Ca0 suggests that the release of calcium from intracellular stores contributes to the increment in Cai seen with ATP depletion. TMB-8, an inhibitor of calcium release from intracellular stores, blunted the rise in Cai by nearly 50%. Neither verapamil nor nifedipine inhibited the rise in Cai. This study demonstrates that ATP depletion induced by the metabolic inhibitors cyanide and 2-deoxy-D-glucose is associated with a rapid and reversible increase in Cai. Both Ca0 influx and Cai redistribution contribute to this rise.
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PMID:Adenosine triphosphate depletion induces a rise in cytosolic free calcium in canine renal epithelial cells. 284 53

Treatment with thromboxane (Tx) synthase inhibitors or free radical scavengers has been shown to afford protection from renal ischemia. Since free radicals are closely associated with thromboxane (Tx) synthesis, this study examines the thesis that free radical scavengers inhibit formation of Tx. Anesthetized rats (n = 42) underwent right nephrectomy. By random choice, before 45 min of left renal pedicle clamping, rats received: 0.5 ml dextrose placebo IV (n = 6); the hydroxyl radical scavenger dimethyl-thiourea (DMTU), 500 mg/kg IV (n = 10); or the superoxide scavenger superoxide dismutase (SOD), 24,000 Sigma Units (SU)/kg IV (n = 12). This dose of SOD was repeated before release of the clamp. Treatment with DMTU and SOD decreased plasma TxB2 levels following 5 min of reperfusion from 2,480 pg/ml in dextrose treated controls to 1,155 pg/ml (p less than 0.01) and 1,419 pg/ml (p less than 0.03), respectively. At 24 hr, DMTU and SOD therapy decreased creatinine from 3.0 mg/dl in controls to 1.6 mg/dl (p less than 0.01) and 2.1 mg/dl (p less than 0.05), respectively. At 24 hr, DMTU but not SOD decreased left renal weight from 113 to 94% (p less than 0.0003) of the weight of the previously removed right kidney, and histologically prevented acute tubular necrosis (p less than 0.05). In nephrectomized but nonischemic sham control rats (n = 7) plasma TxB2 and 6-keto-PGF1 alpha concentrations were 757 pg/ml and 82 pg/ml, creatinine level 0.9 mg/dl and kidney weight 94% of the previously removed right kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of thromboxane (Tx) synthesis by free radical scavengers. 312 99

To determine if moderate hyperglycemia produced by dextrose administration was detrimental in normothermic renal ischemia, 15 halothane-anesthetized mongrel dogs underwent right nephrectomy and 60 minutes of left renal artery and vein occlusion. Six dogs received 1 L of lactated Ringer's solution (LR) and six others received 1 L of 5% dextrose in lactated Ringer's solution (D5LR). Three sham-operated dogs received 1 L of D5LR and underwent right nephrectomy but no occlusions. All dogs received 500 mL of fluid before occlusion and 500 mL after occlusion. The blood glucose concentration for the LR group was 7.6 mmol/L (137 mg/dL) after 500 mL and 7.2 mmol/L (130 mg/dL) after 1000 mL. In the D5LR group, the blood glucose concentration was 21.5 mmol/L (387 mg/dL) after 500 mL and 20.2 mmol/L (363 mg/dL) after 1000 mL. In the sham-operated group, the blood glucose concentration was 22.8 mmol/L (410 mg/dL) after 500 mL and 20.7 mmol/L (373 mg/dL) after 1000 mL. At 30 hours, the plasma creatinine concentration rose from 70 to 300 mumol/L (0.8 to 3.4 mg/dL) in the LR group and from 90 to 500 mumol/L (1.0 to 5.8 mg/dL) in the D5LR group; the increase for the D5LR group was significantly greater than that for the LR group. In the sham-operated group, the plasma creatinine concentration was stable throughout the 30-hour period. This study demonstrates a significant detrimental effect of dextrose administration on renal function during normothermic ischemia.
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PMID:Dextrose administration exacerbates acute renal ischemic damage in anesthetized dogs. 359 69

During renal ischemia, ATP is degraded to hypoxanthine. When xanthine oxidase converts hypoxanthine to xanthine in the presence of molecular oxygen, superoxide radical (O-2) is generated. We studied the role of O-2 and its reduction product OH X in mediating renal injury after ischemia. Male Sprague-Dawley rats underwent right nephrectomy followed by 60 min of occlusion of the left renal artery. The O-2 scavenger superoxide dismutase (SOD) was given 8 min before clamping and before release of the renal artery clamp. Control rats received 5% dextrose instead. Plasma creatinine was lower in SOD treated rats: 1.5, 1.0, and 0.8 mg/dl vs. 2.5, 2.5, and 2.1 mg/dl at 24, 48, and 72 h postischemia. 24 h after ischemia inulin clearance was higher in SOD treated rats than in controls (399 vs. 185 microliter/min). Renal blood flow, measured after ischemia plus 15 min of reflow, was also greater in SOD treated than in control rats. Furthermore, tubular injury, judged histologically in perfusion fixed specimens, was less in SOD treated rats. Rats given SOD inactivated by prior incubation with diethyldithiocarbamate had plasma creatinine values no different from those of control rats. The OH X scavenger dimethylthiourea (DMTU) was given before renal artery occlusion. DMTU treated rats had lower plasma creatinine than did controls: 1.7, 1.7, and 1.3 mg/dl vs. 3.2, 2.2, and 2.4 mg/dl at 24, 48, and 72 h postischemia. Neither SOD nor DMTU caused an increase in renal blood flow, urine flow rate, or solute excretion in normal rats. The xanthine oxidase inhibitor allopurinol was given before ischemia to prevent the generation of oxygen free radicals. Plasma creatinine was lower in allopurinol treated rats: 2.7, 2.2, and 1.4 mg/dl vs. 3.6, 3.5, and 2.3 mg/dl at 24, 48, and 72 h postischemia. Catalase treatment did not protect against renal ischemia, perhaps because its large size limits glomerular filtration and access to the tubular lumen. Superoxide-mediated lipid peroxidation was studied after renal ischemia. 60 min of ischemia did not increase the renal content of the lipid peroxide malondialdehyde, whereas ischemia plus 15 min reflow resulted in a large increase in kidney lipid peroxides. Treatment with SOD before renal ischemia prevented the reflow-induced increase in lipid peroxidation in renal cortical mitochondria but not in crude cortical homogenates. In summary, the oxygen free radical scavengers SOD and DMTU, and allopurinol, which inhibits free radical generation, protected renal function after ischemia. Reperfusion after ischemia resulted in lipid peroxidation; SOD decreased lipid peroxidation in cortical mitochondria after renal ischemia and reflow. We concluded that restoration of oxygen supply to ischemic kidney results in the production of oxygen free radicals, which causes renal injury by lipid peroxidation.
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PMID:Oxygen free radicals in ischemic acute renal failure in the rat. 643 91

The influence of timing of FK 506 (Tacrolimus) administration on renal function and recovery from renal warm ischemia was studied in Sprague-Dawley rats. Animals were administered FK 506 and subjected to 60 min of renal warm ischemia by temporary occlusion of the renal artery and vein. No significant differences in serum creatinine levels among rats subjected to renal ischemia, FK 506, or FK 506 vehicle (methanol and 5% dextrose in water) were demonstrated. In contrast, FK 506 administration (4 mg/kg intraperitoneally) in combination with renal warm ischemia resulted in significant deterioration of renal function with peaking of serum creatinine on day 2. The timing of FK 506 administration relative to renal ischemia did not significantly affect serum creatinine levels. Rats that received FK 506 either 24 hr pre-ischemia, 4 hr pre-ischemia, 4 hr post-ischemia, or 24 hr post-ischemia all showed similar serum creatinine levels on day 2 (3.85 +/- 0.9, 4.7 +/- 0.5, 3.8 +/- 0.9, and 5.1 +/- 0.6 mg/dl, respectively, p = NS). In all animals, serum creatinine returned to baseline values by day 10. Histopathologic examination of kidneys revealed tubular atrophy and dilatation with tubular calcifications at the corticomedullary junction in FK 506 treated animals with or without ischemia. Our data suggest the timing of FK 506 administration in rats subjected to renal warm ischemia does not influence the extent of renal injury with an equally deleterious effect seen when administered within a 24 hr period of an ischemic event. Changes in kidney morphology, however, were seen in all FK 506 treated rats, with or without a period of warm ischemia.
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PMID:Influence of the timing of FK 506 (Tacrolimus) administration on recovery of renal function from warm ischemic injury in rats. 753 42

The 72-kDa heat stress protein (HSP-72) is an inducible cytoprotectant protein. Although transient renal ischemia in vivo induces HSP-72, it is not known whether prior heat stress protects renal epithelial cells from injury mediated by ATP depletion. To evaluate this hypothesis, opossum kidney (OK) cells were exposed to sodium cyanide and 2-deoxy-D-glucose in the absence of medium glucose, a maneuver that reduced cell ATP content to < 10% of the control value within 10 min and decreased cell survival. One day after 2 h of ATP depletion, OK cells previously exposed to heat stress (to induce accumulation of HSP-72) exhibited marked improvement in survival (a > 4-fold increase in total DNA), less uptake of vital dye, and less release of lactate dehydrogenase (LDH) than cells subjected to ATP depletion alone (23.0 +/- 1.6 vs. 34.1 +/- 1.2% of total LDH, respectively). Enhanced clonogenicity post-heat stress was completely prevented by cycloheximide and positively correlated with the steady-state content of HSP-72. In the recovery period after ATP depletion, cell ATP content, maximum mitochondrial ATP production rate, and total LDH activity were all significantly higher in cells with abundant HSP-72. Although the protective effects associated with heat stress are likely to be multifactoral, preserved cell metabolism and higher ATP content could enhance cellular repair processes after ATP depletion.
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PMID:Prior heat stress enhances survival of renal epithelial cells after ATP depletion. 876 25

D-Allose is one of the rare sugars produced from D-psicose. We examined whether d-allose reduces the extent of rat renal ischemia/reperfusion (I/R) injury by suppressing the activation of neutrophils. The renal concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1 and myeloperoxidase were significantly increased after renal I/R. These increases were significantly inhibited by D-allose administration. Furthermore, D-allose significantly inhibited the increase in the concentrations of blood urea nitrogen (BUN), creatinine, N-acetyl beta-D-glucosaminidase (NAG) and histopathologic changes after renal I/R. These findings strongly suggest that D-allose protects against I/R-induced renal injury by inhibiting the activation of neutrophils that play an important role in I/R-induced renal injury. These findings may have important implications in understanding the biologic functions of D-allose. D-Allose may prove useful in renal surgery and transplantation.
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PMID:Inhibitory effect of d-allose on neutrophil activation after rat renal ischemia/reperfusion. 1802 4

D-allose is a monosaccharide. We previously reported that D-allose attenuated renal injury by inhibiting the activation of neutrophils after renal ischemia/reperfusion. Lipopolysaccharide (LPS) triggers sepsis syndrome by activating monocytes to produce proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, which potently stimulates the activation of neutrophils. This study was undertaken to examine the effects of D-allose on renal injury in the systemic inflammatory response induced by LPS administration, with emphasis on systemic TNF-alpha and the activation of neutrophils in the rat kidney. Serum and renal TNF-alpha, renal cytokine-induced neutrophil chemoattractant (CINC)-1, and myeloperoxidase (MPO) concentrations, and renal function after LPS administration were evaluated. D-allose (400 mg/kg body weight) inhibited LPS-induced increases in serum and renal TNF-alpha concentrations and renal CINC-1 and MPO concentrations after LPS administration, as well as the subsequent neutrophil-mediated renal injury. These findings may have important implications in understanding the biologic functions of D-allose. D-allose may prove useful in protecting against acute renal injury in systemic inflammatory responses to LPS.
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PMID:D-allose protects against endotoxemic acute renal injury. 1855 38

The ischemia/reperfusion (I/R) represents a common pathological mechanism that causes renal injuries. A monosaccharide D-allose has been shown to inhibit neutrophil activation, which is involved in the I/R-induced organ injuries. We therefore examined the role of D-ribose in the I/R-induced renal injury using a rat model. D-ribose, a monosaccharide found in all living cells, serves as a key component of adenosine-5'-triphosphate and nicotinamide adenine dinucleotide. Male Wistar rats were divided into the sham, control and D-ribose groups. In the control and D-ribose groups, rats were subjected to 45 min of left renal ischemia, followed by 24 h of reperfusion, while the I/R procedure was not performed in the sham group. Rats were intravenously administered D-ribose (sham group and D-ribose group, 400 mg/kg) or saline (control group) 30 min before ischemia. Blood urea nitrogen (BUN), serum creatinine and urinary N-acetyl beta-D-glucosaminidase (NAG) were measured as indicators of glomerular function and proximal tubular function. We also measured cytokine-induced neutrophil chemoattractant-1 (CINC-1) and myeloperoxidase concentrations to assess neutrophil activation and infiltration, respectively. The tissue sections were scored to evaluate the tubular injury. In the control group, BUN, creatinine, NAG, CINC-1, myeloperoxidase, histological severity score, and number of infiltrating neutrophils were increased following I/R insult, as compared with the sham group. Such increases in biochemical markers, severity score, and infiltrating neutrophils were significantly inhibited in the D-ribose group. Thus, D-ribose ameliorates the I/R-induced renal injury probably by inhibiting neutrophil activation, and may be useful in attenuating the renal injury associated with renal ischemia.
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PMID:D-ribose attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. 1939 71


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