Reactive oxygen molecules, oxidant injury and renal disease

1991 ◽  
Vol 5 (6) ◽  
pp. 733-742 ◽  
Author(s):  
Sharon P. Andreoli
Keyword(s):  
Renal Disease ◽  
Reactive Oxygen ◽  
Oxidant Injury ◽  
Reactive Oxygen Molecules

scholarly journals Fight-or-flight: murine unilateral ureteral obstruction causes extensive proximal tubular degeneration, collecting duct dilatation, and minimal fibrosis

2012 ◽  
Vol 303 (1) ◽  
pp. F120-F129 ◽  
Author(s):  
Michael S. Forbes ◽  
Barbara A. Thornhill ◽  
Jordan J. Minor ◽  
Katherine A. Gordon ◽  
Carolina I. Galarreta ◽  
...  
Keyword(s):  
Renal Disease ◽  
Ureteral Obstruction ◽  
Volume Fraction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Oxidant Injury ◽  
Superoxide Formation ◽  
Atubular Glomeruli ◽  
Proximal Tubular ◽  
Fight Or Flight

Unilateral ureteral obstruction (UUO) is the most widely used animal model of progressive renal disease. Although renal interstitial fibrosis is commonly used as an end point, recent studies reveal that obstructive injury to the glomerulotubular junction leads to the formation of atubular glomeruli. To quantitate the effects of UUO on the remainder of the nephron, renal tubular and interstitial responses were characterized in mice 7 and 14 days after UUO or sham operation under anesthesia. Fractional proximal tubular mass, cell proliferation, and cell death were measured by morphometry. Superoxide formation was identified by nitro blue tetrazolium, and oxidant injury was localized by 4-hydroxynonenol and 8-hydroxydeoxyguanosine. Fractional areas of renal vasculature, interstitial collagen, α-smooth muscle actin, and fibronectin were also measured. After 14 days of UUO, the obstructed kidney loses 19% of parenchymal mass, with a 65% reduction in proximal tubular mass. Superoxide formation is localized to proximal tubules, which undergo oxidant injury, apoptosis, necrosis, and autophagy, with widespread mitochondrial loss, resulting in tubular collapse. In contrast, mitosis and apoptosis increase in dilated collecting ducts, which remain patent through epithelial cell remodeling. Relative vascular volume fraction does not change, and interstitial matrix components do not exceed 15% of total volume fraction of the obstructed kidney. These unique proximal and distal nephron cellular responses reflect differential “fight-or-flight” responses to obstructive injury and provide earlier indexes of renal injury than do interstitial compartment responses. Therapies to prevent or retard progression of renal disease should include targeting proximal tubule injury as well as interstitial fibrosis.

scholarly journals The role of tubular iron accumulation in the remnant kidney.

1994 ◽  
Vol 4 (8) ◽  
pp. 1598-1607
Author(s):  
B J Nankivell ◽  
J Chen ◽  
R A Boadle ◽  
D C Harris
Keyword(s):  
Reactive Oxygen Species ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Iron Chelator ◽  
Iron Accumulation ◽  
Tubular Damage ◽  
Oxygen Species ◽  
Proximal Tubular

Iron has been implicated in the pathophysiology of several models of acute and chronic renal disease. In this study, energy-dispersive x-ray spectrometry was used to quantify and localize iron in rat remnant kidneys (RK) and normal kidneys (NK) and to determine its pathophysiologic significance. Substantial iron accumulation occurred in proximal tubular cell secondary lysosomes of RK (P < 0.001 versus NK) and reached a plateau at 8 wk after partial nephrectomy. In NK, minor increases of iron also occurred with aging (P < 0.02). Proximal tubular iron accumulation correlated independently with protein excretion (r = 0.90) and impairment of GFR (r = 0.70) and was associated with tubular damage and phosphate accumulation (both P < 0.001). Iron nitrilotriacetate (1 mg/kg ip) increased tubular lysosomal iron accumulation and tubular damage (P < 0.001 versus nitrilotriacetate) in NK, comparable to levels seen in untreated RK, and increased cortical cytosolic malondialdehyde, consistent with reactive oxygen species generation. The iron chelator deferoxamine (30 mg/kg per day ip) significantly reduced iron accumulation and tubular damage in RK at 4 wk, compared with deferoxamine chelated to iron and untreated RK. These results suggest that filtered iron enters the remnant tubular lysosomes across the brush border membrane by endocytosis and may produce tubular damage in chronic renal disease by the generation of reactive oxygen species.

Taurine attenuates renal disease in chronic puromycin aminonucleoside nephropathy

1992 ◽  
Vol 262 (1) ◽  
pp. F117-F123 ◽  
Author(s):  
H. Trachtman ◽  
R. Del Pizzo ◽  
S. Futterweit ◽  
D. Levine ◽  
P. S. Rao ◽  
...  
Keyword(s):  
Renal Disease ◽  
Tap Water ◽  
Repeated Administration ◽  
Sprague Dawley ◽  
Tubulointerstitial Injury ◽  
Puromycin Aminonucleoside ◽  
Sprague Dawley Rats ◽  
Taurine Treatment ◽  
Reactive Oxygen Molecules ◽  
Endogenous Antioxidant

Repeated administration of low doses of puromycin aminonucleoside (PAMN) to rats induces a proteinuric renal disease that resembles focal segmental glomerulosclerosis (FSGS). Reactive oxygen molecules may be involved in the progressive course of this nephropathy. Therefore we evaluated whether taurine, an endogenous antioxidant, could limit the extent of renal injury. Sprague-Dawley rats received low-dose injections of PAMN, 2 mg/100 g body wt, over a 12-wk period. Two groups were studied: 1) controls given tap water (n = 23), and 2) an experimental group that drank 1% taurine-supplemented water (n = 22). Taurine-treated nephrotic rats had a reduction in albuminuria, as assessed by the urinary albumin-to-creatinine ratio (26 +/- 4 vs. 44 +/- 4, P less than 0.0001). After 12 wk, creatinine clearance was 0.33 +/- 0.03 (experimental) vs. 0.17 +/- 0.03 ml.min-1.100 g body wt-1 (control) (P less than 0.001), and inulin clearance (n = 6 pairs) was 0.26 +/- 0.04 (experimental) vs. 0.13 +/- 0.02 ml.min-1.100 g body wt-1 (control) (P less than 0.025). Administration of taurine reduced the percentage of segmentally sclerosed glomeruli (9.8 +/- 1.7 vs. 16.2 +/- 1.8%, P less than 0.02) and the tubulointerstitial injury score (1.36 +/- 0.19 vs. 2.61 +/- 0.25, P less than 0.0025) in experimental vs. control rats. Taurine treatment normalized the elevated renal cortical malondialdehyde level in rats with PAMN nephropathy (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Mechanisms for the oxidation of reduced gluthathione by stimulated granulocytes

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 96-104 ◽  
Author(s):  
AL Jr Sagone ◽  
RM Husney ◽  
MS O'Dorisio ◽  
EN Metz
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Hypochlorous Acid ◽  
Reduced Glutathione ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Oxidant Injury ◽  
Cellular Protection ◽  
Human Granulocytes ◽  
Additional Role

Abstract We have reported previously that human granulocytes have an irreversible fall in their endogenous reduced soluble sulfhydryls following zymosan stimulation. In the present study, we demonstrate that stimulated granulocytes release one or more reactive oxygen species (ROS) with the capacity to oxidize reduced glutathione (GSH). One or more of these compounds is stable enough to be detected in the supernatant. The formation of these stable oxidants appears to require H2O2 and heme or a heme-containing enzyme. However, once formed, the compound reacts with GSH without these factors. The ROS is not superoxide or hydroxyl radical, since neither superoxide dismutase nor the hydroxyl scavengers, mannitol and benzoic acid, change the rate of the reaction. Methionine has recently been demonstrated to be oxidized to a sulfoxide by a reactive oxygen species that is dependent on H2O2 and heme for its production. We found that methionine could directly react with the same ROS that degrades GSH. The ROS also has the capacity to oxidize iodide and fix halogen to proteins. Our data indicate that stimulated granulocytes release a ROS with the capacity to oxidize GSH, react with methionine, and oxidize and fix I- to protein. The compound, therefore, appears dependent on H2O2 and the myeloperoxidase system for its production, and is either hypochlorous acid (HOCI) or a compound derived from HOCI, such as a chloramine. The capacity of GSH to react with this ROS suggests an additional role for this tripeptide in cellular protection against oxidant injury.

Oxidant injury alters barrier function of ferret tracheal epithelium

1993 ◽  
Vol 264 (2) ◽  
pp. L165-L174 ◽  
Author(s):  
R. K. McBride ◽  
K. K. Stone ◽  
M. G. Marin
Keyword(s):  
Reactive Oxygen Species ◽  
Ion Transport ◽  
Short Circuit ◽  
Oxidant Stress ◽  
Reactive Oxygen ◽  
Short Circuit Current ◽  
Oxygen Species ◽  
Oxidant Injury ◽  
Active Ion Transport ◽  
Mannitol Flux

To understand the influence of oxidant stress on the barrier function of airway epithelium, we conducted studies to determine the effects of chemically generated reactive oxygen species on permeability, permselectivity, and active ion transport of ferret trachea. We examined the consequences of oxidant injury using ferret trachea mounted in Ussing-type chambers and bathed with a modified Krebs-Henseleit solution containing mannitol and xanthine. We added xanthine oxidase to the luminal bathing solution, which reacted with the xanthine to generate reactive oxygen species. Tissue electrical conductance and short-circuit current were significantly increased after the addition of xanthine oxidase. Simultaneous measurement of mannitol flux (as a marker of paracellular conductance) and the backflux of chloride (lumen to submucosa) demonstrated a significant oxidant-induced increase in mannitol flux and backflux of chloride. Mannitol flux and the backflux of sodium (submucosa to lumen) also increased after oxidant stress. Comparison of the diffusion of sodium relative to the diffusion of chloride in relation to predicted diffusion in free solution indicated that the paracellular pathway was cation selective after oxidant stress. Active ion transport, as reflected by the short-circuit current, was significantly increased transiently after oxidant stress. Studies with furosemide, amiloride, and diphenylamine-2-carboxylate are suggestive that oxidant stress transiently stimulates the Na-K-ATPase. These studies demonstrated that exposure to reactive oxygen species significantly altered the permeability of the tracheal epithelium as well as active ion transport.

scholarly journals Mechanisms for the oxidation of reduced gluthathione by stimulated granulocytes

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 96-104
Author(s):  
AL Jr Sagone ◽  
RM Husney ◽  
MS O'Dorisio ◽  
EN Metz
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Hypochlorous Acid ◽  
Reduced Glutathione ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Oxidant Injury ◽  
Cellular Protection ◽  
Human Granulocytes ◽  
Additional Role

We have reported previously that human granulocytes have an irreversible fall in their endogenous reduced soluble sulfhydryls following zymosan stimulation. In the present study, we demonstrate that stimulated granulocytes release one or more reactive oxygen species (ROS) with the capacity to oxidize reduced glutathione (GSH). One or more of these compounds is stable enough to be detected in the supernatant. The formation of these stable oxidants appears to require H2O2 and heme or a heme-containing enzyme. However, once formed, the compound reacts with GSH without these factors. The ROS is not superoxide or hydroxyl radical, since neither superoxide dismutase nor the hydroxyl scavengers, mannitol and benzoic acid, change the rate of the reaction. Methionine has recently been demonstrated to be oxidized to a sulfoxide by a reactive oxygen species that is dependent on H2O2 and heme for its production. We found that methionine could directly react with the same ROS that degrades GSH. The ROS also has the capacity to oxidize iodide and fix halogen to proteins. Our data indicate that stimulated granulocytes release a ROS with the capacity to oxidize GSH, react with methionine, and oxidize and fix I- to protein. The compound, therefore, appears dependent on H2O2 and the myeloperoxidase system for its production, and is either hypochlorous acid (HOCI) or a compound derived from HOCI, such as a chloramine. The capacity of GSH to react with this ROS suggests an additional role for this tripeptide in cellular protection against oxidant injury.

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