Effects of chitosan oligosaccharide (COS) on the glycerol-induced acute renal failure in vitro and in vivo

2008 ◽  
Vol 46 (2) ◽  
pp. 710-716 ◽  
Author(s):  
Hyun Joong Yoon ◽  
Myoung E. Moon ◽  
Haeng Soon Park ◽  
Hyun Woo Kim ◽  
Shun Young Im ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Chitosan Oligosaccharide

Enhanced skeletal muscle arteriolar reactivity to ANG II after recovery from ischemic acute renal failure

2005 ◽  
Vol 289 (6) ◽  
pp. R1770-R1776 ◽  
Author(s):  
David P. Basile ◽  
Deborah L. Donohoe ◽  
Shane A. Phillips ◽  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Pressor Response ◽  
Gracilis Muscle ◽  
Ang Ii ◽  
Sprague Dawley

In addition to the long-term renal complications, previous studies suggested that after acute renal failure (ARF), rats manifest an increased pressor response to an overnight infusion of ANG II. The present study tested whether recovery from ARF results in alterations in sensitivity to the peripheral vasculature. ARF was induced in Sprague-Dawley rats by 45 min of bilateral renal ischemia and reperfusion. Animals were allowed to recover renal structure and function for 5–8 wk, after which the acute pressor responses to ANG II were evaluated either in vivo in in situ skeletal muscle arterioles or in isolated gracilis muscle arteries in vitro. Baseline arterial pressure was not different in ARF rats vs. sham-operated controls, although ARF rats exhibited an enhanced pressor response to bolus ANG II infusion compared with control rats. Steady-state plasma ANG II concentration and plasma renin activity were similar between ARF and control rats. Constrictor reactivity of in situ cremasteric arterioles from ARF rats was enhanced in response to increasing concentrations of ANG II; however, no difference was observed in arteriolar responses to elevated Po2, norepinephrine, acetylcholine, or sodium nitroprusside. Isolated gracilis muscle arteries from ARF rats also showed increased vasoconstriction in response to ANG II but not norepinephrine. In conclusion, recovery from ischemic ARF is not associated with hypertension but is associated with increased arteriolar constrictor reactivity to ANG II. Although the mechanisms of this altered responsiveness are unclear, such changes may relate, in part, to cardiovascular complications in patients with ARF and/or after renal transplant.

In vitro versus in vivo mitochondrial calcium loading in ischemic acute renal failure

1985 ◽  
Vol 248 (6) ◽  
pp. F845-F850
Author(s):  
P. E. Arnold ◽  
D. Lumlertgul ◽  
T. J. Burke ◽  
R. W. Schrier
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Ruthenium Red ◽  
Respiratory Dysfunction ◽  
Calcium Loading ◽  
Ischemic Tissue ◽  
High Concentrations ◽  
Ischemic Acute Renal Failure

Progressive mitochondrial Ca2+ accumulation and respiratory dysfunction have been observed during reperfusion after renal ischemia. The present study demonstrated that normal mitochondria, isolated in the presence of high Ca2+ concentrations, are capable of accumulating large amounts of Ca2+ in vitro and exhibit depressed respiratory rates. Since mitochondria isolated from reperfused ischemic tissue may be exposed to high concentrations of Ca2+ during the isolation procedure, the present study examined the effect of in vitro versus in vivo mitochondrial Ca2+ loading on mitochondrial function during ischemic acute renal failure (ARF) in anesthetized rats. When ruthenium red was added during isolation to prevent mitochondrial Ca2+ exchange with the medium, mitochondrial Ca2+ increased from 10.8 +/- 0.3 to 65.6 +/- 11.6 nmol/mg (P less than 0.001) after 24 h of postischemic reperfusion; this resulted in a 47% reduction in the acceptor-control ratio (ACR) from 4.19 +/- 0.09 to 2.70 +/- 0.13 (P less than 0.001). These data were compared with an increase in mitochondrial Ca2+ from 52.5 +/- 2.9 to 167.6 +/- 25.4 nmol/mg (P less than 0.001) and a 95% fall in ACR (3.84 +/- 0.40 to 1.15 +/- 0.08, P less than 0.001) at 24 h of reperfusion when no ruthenium red was added. However, at each time point examined, in vivo mitochondrial Ca2+ accumulation was shown to account for 50% or more of the mitochondrial respiratory dysfunction observed during ischemic ARF.

scholarly journals In vitro and in vivo protective effect of atriopeptin III on ischemic acute renal failure.

1987 ◽  
Vol 80 (3) ◽  
pp. 698-705 ◽  
Author(s):  
M Nakamoto ◽  
J I Shapiro ◽  
P F Shanley ◽  
L Chan ◽  
R W Schrier
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Protective Effect ◽  
Ischemic Acute Renal Failure

scholarly journals The influence of mannitol on myoglobinuric acute renal failure: functional, biochemical, and morphological assessments.

1991 ◽  
Vol 2 (4) ◽  
pp. 848-855
Author(s):  
R A Zager ◽  
C Foerder ◽  
C Bredl
Keyword(s):  
Lipid Peroxidation ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Membrane Vesicles ◽  
Tubular Cell ◽  
Protective Effects ◽  
Beneficial Action ◽  
Cellular Energetics

This study was undertaken to explore the protective influence of mannitol against the glycerol model of myohemoglobinuric acute renal failure. Three hypotheses were tested: (1) mannitol confers cytoprotection by acutely blunting renal hypoperfusion, thereby improving tubular cell energetics; (2) as an hydroxyl radical (OH.) scavenger, mannitol mitigates Fe-driven lipid peroxidation and, hence, decreases tubular cell necrosis; and (3) mannitol prevents intrarenal heme pigment trapping, decreasing cast formation. Rats were injected with 50% glycerol (10 mL/kg im), followed immediately by an iv mannitol (1.25 mL/100 g over 1 h) or sham infusion. Mannitol induced a brisk diuresis (approximately 5.7 mL/2 h; approximately 35 mg of heme protein excreted), whereas glycerol controls were anuric. Mannitol did not significantly increase postglycerol RBF (2.8 mL/min), and it paradoxically worsened cellular energetics, halving cortical ATP concentrations at 1 h. However, this adverse effect on ATP was transient, correlating with active diuresis. Glycerol did not induce convincing in vivo lipid peroxidation (malondialdehyde; conjugated diene assay), and mannitol did not block Fe-driven in vitro lipid peroxidation of isolated brush border membrane vesicles. Na benzoate, an OH. scavenger, conferred no in vivo or in vitro protection. However, Na2SO4, not an OH. scavenger, reproduced the diuretic and in vivo protective effects of mannitol. Purified myoglobin infusion (35 mg) largely negated the beneficial action of mannitol. It was concluded that mannitol confers functional but not cytoprotection against the glycerol acute renal failure model, it acutely worsens renal bioenergetics, and its protective influence is probably due to a diuretic, not an antioxidant, effect.

Coordination of the cell cycle is an important determinant of the syndrome of acute renal failure

2002 ◽  
Vol 283 (4) ◽  
pp. F810-F816 ◽  
Author(s):  
Judit Megyesi ◽  
Lucia Andrade ◽  
Jose M. Vieira ◽  
Robert L. Safirstein ◽  
Peter M. Price
Keyword(s):  
Cell Cycle ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
In Vitro Models ◽  
Severe Renal Failure ◽  
Differentiated Cells ◽  
Tissue Recovery ◽  
Cell Cycle Inhibitors

Recovery from injury is usually accompanied by cell replication, in which new cells replace those irreparably damaged. After acute renal failure, normally quiescent kidney cells enter the cell cycle, which in tubule segments is accompanied by the induction of cell cycle inhibitors. We found that after acute renal failure induced by either cisplatin injection or renal ischemia, induction of the p21 cyclin-dependent kinase (cdk) inhibitor is protective. Mice lacking this gene developed more widespread kidney cell death, more severe renal failure, and had reduced survival, compared with mice with a functional p21gene. Here, we show induction of 14-3-3ς, a regulator of G2-to-M transition, after acute renal failure. Our findings, using both in vivo and in vitro models of acute renal failure, show that this protein likely helps to coordinate cell cycle activity to maximize recovery of renal epithelial cells from injury and reduce the extent of the injury itself. Because in terminally differentiated cells, these proteins are highly expressed only after injury, we propose that cell cycle coordination by induction of these proteins could be a general model of tissue recovery from stress and injury.

Levosimendan protects against experimental endotoxemic acute renal failure

2006 ◽  
Vol 290 (6) ◽  
pp. F1453-F1462 ◽  
Author(s):  
Richard A. Zager ◽  
Ali C. Johnson ◽  
Steve Lund ◽  
Sherry Y. Hanson ◽  
Christine K. Abrass
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Sepsis Syndrome ◽  
Atp Depletion ◽  
Ang Ii ◽  
Tubular Injury ◽  
Renal Vasoconstriction ◽  
Channel Opening

Endotoxemia induces a hemodynamic form of acute renal failure (ARF; renal vasoconstriction ± reduced glomerular ultrafiltration coefficient, Kf; minimal/no histological damage). We tested whether levosimendan (LS), an ATP-sensitive K+ (KATP) channel opener with cardiac ionotropic and possible anti-inflammatory properties, might have utility in combating this form of ARF. CD-1 mice were injected with LPS ± LS. LS effects on LPS-induced systemic inflammation (plasma TNF-α/MCP-1; cardiorenal mRNAs), plasma NO levels, and azotemia were assessed. Because KATP channel opening has been reported to mediate hypoxic tubular injury, possible adverse LS effects on ischemic ARF and ATP depletion injury were sought. Effects of diazoxide (another KATP channel agonist) and glibenclamide (a channel antagonist) on hypoxic tubular injury also were assessed. Finally, the ability of LS to alter rat mesangial cell (MC) contraction in response to ANG II (elevated in sepsis) was tested. LS conferred almost complete protection against LPS-induced ARF, without any apparent reduction in the LPS-induced inflammatory response. Neither LS nor diazoxide altered ATP depletion-mediated tubule injury (in vivo or in vitro). Conversely, glibenclamide induced a marked and direct cytotoxic effect. LS completely blocked ANG II-induced MC contraction, an action likely to increase Kf. We concluded that 1) LS can confer marked protection against LPS-induced ARF; 2) this likely stems from vasoactive properties, rather than reductions in LPS-induced inflammation; and 3) KATP channel agonists (but not antagonists) appear to be devoid of toxic proximal tubular cell effects. This suggests that LS, and other KATP channel agonists, have a margin of safety if employed in situations (sepsis syndrome, heart failure) in which severe renal vasoconstriction might lead to ischemic ARF.

scholarly journals Protection of renal cells from cisplatin toxicity by cell cycle inhibitors

2004 ◽  
Vol 286 (2) ◽  
pp. F378-F384 ◽  
Author(s):  
Peter M. Price ◽  
Robert L. Safirstein ◽  
Judit Megyesi
Keyword(s):  
Cell Cycle ◽  
Renal Failure ◽  
Cell Death ◽  
Acute Renal Failure ◽  
Proximal Tubule ◽  
Selective Inhibition ◽  
Proximal Tubule Cell ◽  
Cell Cycle Inhibitors

The optimal use of cisplatin as a chemotherapeutic drug has been limited by its nephrotoxicity. Murine models have been used to study cisplatin-induced acute renal failure. After cisplatin administration, cells of the S3 segment in the renal proximal tubule are especially sensitive and undergo extensive necrosis in vivo. Similarly, cultured proximal tubule cells undergo apoptosis in vitro after cisplatin exposure. We have shown in vivo that kidney cells enter the cell cycle after cisplatin administration but that cell cycle-inhibitory proteins p21 and 14-3-3σ are also upregulated. These proteins coordinate the cell cycle, and deletion of either of the genes resulted in increased nephrotoxicity in vivo or increased cell death in vitro after exposure to cisplatin. However, it was not known whether cell cycle inhibition before acute renal failure could protect from cisplatin-induced cell death, especially in cells with functional p21 and 14-3-3σ genes. Using several cell cycle inhibitors, including a p21 adenovirus, and the drugs roscovitine and olomoucine, we have been able to completely protect a mouse kidney proximal tubule cell culture from cisplatin-induced apoptosis. The protection by p21 was independent of an effect on the cell cycle and was likely caused by selective inhibition of caspase-dependent and -independent cell death pathways in the cells.

Rapamycin impairs recovery from acute renal failure: role of cell-cycle arrest and apoptosis of tubular cells

2001 ◽  
Vol 281 (4) ◽  
pp. F693-F706 ◽  
Author(s):  
Wilfred Lieberthal ◽  
Robert Fuhro ◽  
C. Christopher Andry ◽  
Helmut Rennke ◽  
Vivian E. Abernathy ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Interleukin 2 ◽  
Cell Loss ◽  
Tubular Cells

The immunosuppressive effect of rapamycin is mediated by inhibition of interleukin-2-stimulated T cell proliferation. We report for the first time that rapamycin also inhibits growth factor-induced proliferation of cultured mouse proximal tubular (MPT; IC50 ∼1 ng/ml) cells and promotes apoptosis of these cells by impairing the survival effects of the same growth factors. On the basis of these in vitro data, we tested the hypothesis that rapamycin would impair recovery of renal function after ischemic acute renal failure induced in vivo by renal artery occlusion (RAO). Rats given daily injections of rapamycin or vehicle were subjected to RAO or sham surgery. Rapamycin had no effect on the glomerular filtration rate (GFR) of sham-operated animals. In rats subjected to RAO, GFR fell to comparable levels 1 day later in vehicle- and rapamycin-treated rats (0.25 ± 0.08 and 0.12 ± 0.05 ml · min−1 · 300 g−1, respectively) ( P = not significant). In vehicle-treated rats subjected to RAO, GFR increased to 0.61 ± 0.08 ml · min−1 · 300 g−1 on day 3 ( P < 0.02 vs. day 1) and then rose further to 0.99 ± 0.09 ml · min−1 · 300 g−1 on day 4 ( P < 0.02 vs. day 3). By contrast, GFR did not improve in rapamycin-treated rats subjected to RAO over the same time period. Rapamycin also increased apoptosis of tubular cells while markedly reducing their proliferative response after RAO. Furthermore, rapamycin inhibited activation of 70-kDa S6 protein kinase (p70S6k) in cultured MPT cells as well as in the renal tissue of rats subjected to RAO. We conclude that rapamycin severely impairs the recovery of renal function after ischemia-reperfusion injury. This effect appears to be due to the combined effects of increased tubular cell loss (via apoptosis) and profound inhibition of the regenerative response of tubular cells. These effects are likely mediated by inhibition of p70S6k.

Evidence for an Increased Generation of Prostacyclin in the Microvasculature and an Impairment of the Platelet α-Granule Release in Chronic Renal Failure

1988 ◽  
Vol 60 (02) ◽  
pp. 205-208 ◽  
Author(s):  
Paul A Kyrle ◽  
Felix Stockenhuber ◽  
Brigitte Brenner ◽  
Heinz Gössinger ◽  
Christian Korninger ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Blood Clotting ◽  
Normal Subjects ◽  
Chronic Uraemia ◽  
Wall Interaction ◽  
End Stage ◽  
Granule Release

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.

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