Priming prevent nephrotoxic acute renal failure through stimulation of antioxidant defense mechanism

Although ischemia remains the leading cause of acute renal failure in humans, there is little information on the expression and activities of gelatinases of kidney glomeruli during ischemia–reperfusion injury. In this study, we used a unilateral ischemia–reperfusion model to investigate the activity and expression of gelatinases in glomeruli during acute ischemia. Unilateral ischemia was induced in rats by vascular clamping (30 min) followed by reperfusion (60 min) and isolation of glomeruli. The activity and expression of gelatinase proteins were determined by gelatin zymography and Western blotting. Gelatinase mRNA levels were evaluated by reverse transciptase-PCR. Ischemia and reperfusion increased serum creatinine levels, hallmark of acute renal failure. Ischemia induced mRNA and protein MMP-2 expression. There was strong stimulation of MMP-9 mRNA, both forms of dimeric MMP-9, and active mono meric MMP-9. In contrast to TIMP-1 decreasing, TIMP-2 protein and mRNA increased during ischemia. During reperfusion, there was a gradual reversal of the MMP-2 and MMP-9 levels and a strong inhibition of TIMP-1 and TIMP-2 at the protein and mRNA levels. Endocytic receptor LRP was increased during ischemia and returned to normal during reperfusion. Expression of MMP-9 docking receptor CD-44 was increased during reperfusion. Finally, ZO-1, an in vivo MMP-9 substrate, was degraded during ischemia, revealing that MMP-9 upregulated during ischemia was functional. Our data suggest that stimulation of gelatinase activity during ischemia could contribute to glomeruli injury, providing new therapeutic targets for acute renal failure in humans. In contrast, elevated monomeric MMP-9 activity due to TIMP-1 decrease during reperfusion may participate to glomerular recovery.Key words: gelatinases, ischemia-reperfusion, TIMPs, ZO-1, CD-44, LRP, glomeruli.

Download Full-text

The Role of Oxygen Free Radicals in Acute Renal Failure Complicating Obstructive Jaundice: An Experimental Study

HPB Surgery ◽

10.1155/1998/47363 ◽

1998 ◽

Vol 10 (6) ◽

pp. 387-393 ◽

Cited By ~ 7

Author(s):

Serdar Yüceyar ◽

Koray Gümüştaş ◽

Süphan Ertürk ◽

Ismail H. Hamzaoğlu ◽

Nesrin Uygun ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Free Radicals ◽

Obstructive Jaundice ◽

Renal Cortex ◽

Defense Mechanism ◽

Oxygen Free Radicals ◽

Statistical Significance ◽

Renal Ischemia

Oxydant injury is considered to be an important mechanism in the pathophysiology of acute renal failure. It has been thought that decrease in extracellular and intracellular fluid and endotoxemia seen in obstructive jaundice may cause an increase in production of oxygen free radicals and impairment in antioxydant defense mechanism. This study is designed to investigate the possible role of oxydant injury in renal failure seen in jaundiced patients. In this study, 28 rats were divided into four groups: Control(C) (N=7); Renal ischemia (RI) (N=7); Obstructive jaundice+renal ischemia (OJ+RI) (N=7); Obstructive jaundice (OJ) (N=7). All groups were compared with each other according to renal failure findings and enzyme activities, such as Xanthine oxidase (XOD), Superoxide Dismutase (SOD) and Catalase in renal cortex and Glutathione Peroxidase (GSH-Px), in blood at 3rd day after ischemia and reperfusion. Renal failure findings monitored by blood urea and creatinine levels, seemed more evident in OJ+RI than RI group (p <0.05). When compared with RI, in OJ+RI group, increase in XOD activity at 3rd day was statistically significant [0.259 ±0.01 U/g (tissue) and 0.362±0.03 U/g (tissue) respectively] (p <0.05). SOD and GSH-Px activities of each ischemic group at 3rd day were decreased compared to non-ischemic groups. This fall was significant (p <0.05). But there was no statistical difference between jaundiced and non-jaundiced groups. Alterations in catalase activities also had no statistical significance.These findings may suggest that the injury induced by oxygen free radicals at re-oxygenation of tissue after ischemia may also play a role in the pathogenesis of acute renal failure developed in obstructive jaundice.

Download Full-text

Canine renal cortical necrosis and haemorrhage following ingestion of an Amitraz-formulated insecticide dip : clinical communication

Journal of the South African Veterinary Association ◽

10.4102/jsava.v77i3.366 ◽

2006 ◽

Vol 77 (3) ◽

Cited By ~ 4

Author(s):

P.A. Oglesby ◽

K.E. Joubert ◽

T. Meiring

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Veterinary Medicine ◽

Case Report ◽

Adrenergic Receptors ◽

Clinical Signs ◽

Clinical Communication ◽

Cortical Necrosis ◽

Adrenergic Antagonists ◽

Stimulation Of

Amitraz is a formamidine compound used in veterinary medicine as a topical dip to control ticks and mites on dogs and livestock. A 10-year-old female Scottish terrier was presented following the accidental oral administration of a dip containing amitraz. This case report describes the clinical signs, treatment and pathology of this dog. Clinical signs of toxicity from amitraz result from stimulation of alpha2-adrenergic receptors. Amitraz is seldom fatal because the effects can be reversed by alpha2-adrenergic antagonists. The dog recovered from the amitraz toxicity but died 5 days later from acute renal failure.

Download Full-text