The role of adenosine in HgCl2-induced acute renal failure in rats

1990 ◽  
Vol 258 (6) ◽  
pp. F1554-F1560 ◽  
Author(s):  
N. Rossi ◽  
V. Ellis ◽  
T. Kontry ◽  
S. Gunther ◽  
P. Churchill ◽  
...  

It has been proposed that adenosine mediates the renal hemodynamic changes in acute renal failure (ARF) and that these changes are pathogenic in reducing glomerular filtration rate. Consistently, adenosine-receptor antagonists such as theophylline have been shown to have protective effects in several experimental models of ARF. The present experiments were designed to explore the potential role of adenosine in HgCl2-induced ARF in rats. In isolated perfused rat kidneys, HgCl2 increased adenosine production and induced a concentration-dependent vasoconstriction. However, the vasoconstriction was unrelated to adenosine production and was not antagonized by theophylline. During the initiation phase of HgCl2-induced ARF in intact rats (first 4 h after injection), theophylline failed to reverse the reduction in inulin clearance, and this failure could not be attributed to a loss of vascular responsiveness to adenosine, since N6-cyclohexyladenosine, a receptor agonist, produced a further reduction in inulin clearance. Furthermore, theophylline actually had deleterious effects during the maintenance phase of HgCl2-induced ARF in intact unanesthetized rats, as evidenced by higher mean serum creatinine values in theophylline-injected rather than in saline-injected rats, on both the second and third days after HgCl2 injection. Therefore HgCl2 acutely increases renal adenosine production, but increased adenosine does not mediate acute HgCl2-induced renal vasoconstriction, and adenosine-receptor antagonism does not have protective effects during the initiation or the maintenance phases of HgCl2-induced ARF in rats. These results provide no support for the hypothesis that increased adenosine mediates the hemodynamic changes in HgCl2-induced ARF.

2000 ◽  
Vol 279 (1) ◽  
pp. F3-F11 ◽  

This review, which is the final installment in a series devoted to controversial issues in acute renal failure (ARF) (3, 47), will examine available information regarding the role of growth factors in ARF. In general, studies in this area have fallen into two broad categories: 1) those that have examined the renal expression of genes encoding growth factors or transcriptional factors associated with the growth response that is induced after ARF, and 2) those that have examined the efficacy of exogenously administered growth factors in accelerating recovery of renal function in experimental models of ARF. Despite the vast amount of information that has accumulated in these two areas of investigation, our understanding of the mechanisms involved in the process of regeneration and repair after ARF, and the role of growth factors in this response, remains rudimentary. This overview, contributed to by a number of experts in the field, is designed to summarize present knowledge and to highlight potentially fertile areas for future research in this area.


2016 ◽  
Vol 4 (3) ◽  
pp. 329-336 ◽  
Author(s):  
Ahmed Atwa ◽  
Rehab Hegazy ◽  
Nermeen Shaffie ◽  
Neamat Yassin ◽  
Sanaa Kenawy

BACKGROUND: Rhabdomyolysis (RM)-induced acute renal failure (ARF) accounts for about 10–40% of all cases of ARF.AIM: The present study investigated the possible protective effect of two nitric oxides (NO)-releasing third generation β-blockers, carvedilol (Carv) and nebivolol (Nebi), against RM-mimicking glycerol (Gly)-induced ARF in rats.MATERIAL AND METHODS: After 24 h dehydration, rats received a single dose of 50% Gly (8 ml/kg, im). They were treated with vehicle, Carv (2.5 mg/kg/day, po) or Nebi (10 mg/kg, po) for 3 successive days starting from an hour prior to Gly injection. Evaluation of blood pressure and locomotor activity was performed during the experiment. 72 h following Gly administration, total protein in the urine, serum levels of creatinine, blood urea nitrogen, sodium and potassium as well as the renal contents of malondialdehyde, reduced glutathione and NO were assessed, together with a histopathological examination of renal tissues.RESULTS: Carv and Nebi attenuated Gly-induced renal dysfunction and histopathological alterations. They decreased the Gly-induced oxidative stress and increased renal NO concentration. Restoration of normal blood pressure and improvement of locomotor activity were also observed.CONCLUSION: The results clearly demonstrate protective effects of Carv and Nebi against renal damage involved in RM-induced ARF and suggest a role of their antioxidant and NO-releasing properties.


1983 ◽  
Vol 61 (6) ◽  
pp. 567-571 ◽  
Author(s):  
K. Bidani ◽  
P. C. Churchill

The effect of aminophylline (theophylline complexed with ethylenediamine) on the severity of glycerol-induced myohemoglobinuric acute renal failure was examined in rats. In the first series of experiments, one group of rats received twice daily injections of aminophylline following the induction of acute renal failure, and a second group (controls) received twice daily injections of saline. Only one of the aminophylline-injected rats but five of the saline-injected rats died during the 3-day follow-up period. Moreover, mean serum creatinine was lower in the aminophylline-injected rats than in the saline-injected controls on each of the 3 days, demonstrating that aminophylline reduced the renal functional impairment. In the second series, single injections of aminophylline were given at the time of glycerol injections or 3, 6, or 24 h later. As assessed by mean serum creatinine during the 3-day follow up, even single injections had protective effects if given during the initiation phase (0–3 h after glycerol). Since aminophylline dissociates into theophylline in biological fluids, and since theophylline is an adenosine-receptor antagonist, these observations are consistent with the hypothesis that adenosine plays a pathogenic role in myohemoglobinuric acute renal failure in rats.


1988 ◽  
Vol 255 (3) ◽  
pp. F539-F544 ◽  
Author(s):  
M. S. Paller

In ischemic acute renal failure oxygen free radicals may mediate injury. In addition, iron appears to play a critical role in hydroxyl radical formation and lipid peroxidation during reperfusion of ischemic kidneys. To determine whether iron may play a similar role in pigment (heme protein)-induced acute renal failure, we studied the effects of the iron chelator deferoxamine in two experimental models of pigment-induced acute renal failure, intramuscular glycerol injection and intravenous hemoglobin infusion without and with concurrent ischemia in the rat. Intramuscular injection of 50% glycerol (5 ml/kg) caused inulin clearance to fall to 0.13 +/- 0.03 (SE) ml/min (normal value, 1.0–1.2 ml/min). Continuous infusion of deferoxamine beginning at the time of glycerol injection significantly attenuated this renal dysfunction. Deferoxamine-treated animals had an inulin clearance of 0.37 +/- 0.06 ml/min (P less than 0.01). Glycerol injection was also associated with significant lipid peroxidation, measured as renal malondialdehyde content. Deferoxamine-treated glycerol-injected rats had renal malondialdehyde content not significantly different from control animals. In another model of heme pigment-induced renal injury, hemoglobin was infused to produce hemoglobinuria. Inulin clearance 1 h after hemoglobin infusion was significantly reduced to 0.84 +/- 0.5 ml/min (P less than 0.025). Infusion of deferoxamine after hemoglobin prevented the hemoglobin-induced decrease in inulin clearance. Thirty minutes of renal ischemia followed by infusion of hemoglobin resulted in more severe renal dysfunction with inulin clearance of 0.54 +/- 0.08 ml/min. Deferoxamine infused at the time of reperfusion attenuated the fall in glomerular filtration rate after ischemia and hemoglobin infusion:inulin clearance 1.04 +/- 0.07 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)


2002 ◽  
Vol 103 (s2002) ◽  
pp. 434S-437S ◽  
Author(s):  
Masanori TAKAOKA ◽  
Mikihiro YUBA ◽  
Toshihide FUJII ◽  
Mamoru OHKITA ◽  
Yasuo MATSUMURA

We investigated whether the treatment with 17β-oestradiol has renal protective effects in male rats with ischaemic acute renal failure (ARF). We also examined if the effect of 17β-oestradiol is accompanied by suppression of enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was induced by clamping the left renal artery and vein for 45min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine and creatinine clearance were measured to test the effectiveness of the steroid hormone. Renal function in ARF rats markedly decreased 24h after reperfusion. The ischaemia/reperfusion-induced renal dysfunction was dose-dependently improved by pretreatment with 17β-oestradiol (20 or 100µg/kg, intravenously). Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were markedly improved by the higher dose of 17β-oestradiol. In addition, endothelin-1 content in the kidney after the ischaemia/reperfusion increased significantly by approx. 2-fold over sham-operated rats, and this elevation was dose-dependently suppressed by the 17β-oestradiol treatment. These results suggest that oestrogen exhibits protective effects against renal dysfunction and tissue injury induced by ischaemia/reperfusion, possibly through the suppression of endothelin-1 overproduction in postischaemic kidneys.


Renal Failure ◽  
2007 ◽  
Vol 29 (3) ◽  
pp. 379-386 ◽  
Author(s):  
Alessio Sturiale ◽  
Susanna Campo ◽  
Eleonora Crascì ◽  
Carmela Aloisi ◽  
Michele Buemi

2004 ◽  
Vol 19 (1) ◽  
pp. 93-96 ◽  
Author(s):  
Rachita Nanda ◽  
Pramila K. Mishra ◽  
U. K. Das ◽  
S. B. Rout ◽  
P. C. Mohapatra ◽  
...  

2002 ◽  
Vol 36 (9) ◽  
pp. 1466-1470 ◽  
Author(s):  
Donald F Brophy

OBJECTIVE: To examine the role of N-acetylcysteine (NAC) in the prevention of radiocontrast—induced nephropathy (RIN). DATA SOURCES: A literature search of MEDLINE (1966–December 2001) was performed using the following search terms: N-acetylcysteine, nephropathy, acute renal failure, and radiocontrast. STUDY SELECTION: Pertinent English-language animal and human studies were reviewed. DATA SYNTHESIS: Few small animal trials have demonstrated that NAC significantly prevents the development or reduces the severity of acute renal failure. Two human studies demonstrated NAC significantly reduces the occurrence of RIN. CONCLUSIONS: NAC may reduce the occurrence of RIN in high-risk patients. Further large-scale studies are needed to corroborate findings from earlier trials.


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