Renal failure following perinatal anoxia

Dauber, Ira; Krauss, Alfred N.; Symchych, Paul S.; Auld, Peter A. M.

doi:10.1016/s0022-3476(76)81130-4

Cited by 109 publications

(48 citation statements)

References 12 publications

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“…Accumulating experimental evidence suggests that ischemia-reperfusion injury mediated by active oxygen species can be a mechanism of renal tubular damage, leading to acute tubular necrosis (3,23). Perinatal asphyxia and hypoxia is known to accompany ischemic renal dysfunction (24). We cannot extrapolate the development of antioxidant enzymes in human fetus from the results obtained in the rat.…”

Section: Resultsmentioning

confidence: 95%

Prenatal Development of Antioxidant Enzymes in Rat Lung, Kidney, and Heart: Marked Increase in Immunoreactive Superoxide Dismutases, Glutathione Peroxidase, and Catalase in the Kidney

et al. 1990

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ABSTRACT. The immaturity of antioxidant capacity in sion injury involving a variety of organs including heart (2) and the lung in preterm newborn infants is postulated to con-kidney (3). The antioxidant enzymes, comprised of cytosolic tribute to the development of hyperoxic lung injury. An-CuZnSOD, mitochondrial MnSOD (EC 1.15.1. I), GPX (EC tioxidant enzymes in fetal lung, comprised of copper-zinc 1.1 1.1.9), and CAT (EC 1.1 1.1.6), afford protection by reducing (cytosolic) and manganese (mitochondrial) superoxide dis-the cellular concentration of active oxygen species (4). In special mutases, glutathione peroxidase, and catalase, have been relevance to bronchopulmonary dysplasia, several previous studreported to increase during the late gestational period. To ies focused on prenatal development of pulmonary antioxidant determine whether such maturation of antioxidant capacity enzymes in the rat (5-8). The activities of total SOD, GPX, and occurs in other tissues, we have evaluated the development CAT in lung were invariably found to be low before term and of these four enzymes from d 18 to 22 of gestation in rat the low activities are considered to account, in part, for the lung, kidney, and heart. To resolve the confusion in the vulnerability of premature newborn lung to hyperoxia. However, reported levels of lung superoxide dismutases, the two the two SOD isoenzymes were measured in only two previous isoenymes were assayed separately by specific RIA. The studies (7,8) and the data were conflicting. growth of the kidney exceeded that of the whole body Part of the confusion is due to the limited sensitivity and during this period, while the growth of the lung and heart specificity of the biologic SOD activity assays generally used. The did not. The concentrations of the four antioxidant enzymes activity assays detect all SOD-like activities, and are not specific in lung and kidney increased in a stepwise manner during to each form of intracellular SOD. Furthermore, a relatively low this period, and the magnitude of the change for each concentration of MnSOD in the tissues of rats compared with enzyme was greater in the kidney than in the lung. On the that in other species (9) makes biologic activity assays more other hand, the only significant change in the concentra-prone to interference when applied to rat tissue homogenate. tions of heart antioxidant enzymes observed was a mild The specific RIA for rat MnSOD and CuZnSOD (10) have increase in the glutathione peroxidase concentration from obviated the concerns regarding activity assays for SOD, although d 20 to 22. These results suggest that the prenatal matu-they do not measure biological activity. These assays have enration of antioxidant capacity occurs earlier in the heart abled us to measure CuZnSOD and MnSOD accurately not only and later in the kidney than in the lung, and that the in fetal lung, but also in smaller tissues in fetal rat. immaturity of antioxidant capacity could make the fetal In our present study, we evaluated the development of Curat k...

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Section: Resultsmentioning

confidence: 95%

Prenatal Development of Antioxidant Enzymes in Rat Lung, Kidney, and Heart: Marked Increase in Immunoreactive Superoxide Dismutases, Glutathione Peroxidase, and Catalase in the Kidney

et al. 1990

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“…Proximal renal tubular cells are highly sensitive to hypoxia, and proximal tubular necrosis (Fig. ld) may partly be a consequence of pulmonary failure (64). Thus, mortality of GSH-deficient newborn rats may be ascribed to functional defects in one or more organs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress.

Mårtensson

Jain

Stole

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

174

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A model for oxidative stress is described in which glutathione (GSH) synthesis is selectively blocked in newborn rats by administration of L-buthionine-(SR)-sulfoxipuine (BSO). In this model, the normal endogenous physiological formation of reactive oxygen species is largely unopposed, and therefore oxidative tissue damage occurs; because GSH is used for reduction of dehydroascorbate, tissue ascorbate levels decrease. In lung there are decreased numbers of Isieflar bodies and decrease of intraalveolar surfactant. Proximal renal tubular, hepatic, and brain damage also occur. A diastereolsomer of BSO that does not inhibit GSH synthesis, L-buthiflR-sulfoximine, does not produce toxicity; this control experiment renders it unlikely that the observed effects of BSO are produced by the sulfoximine moiety itself. There is correlation between the decrease of mitochondrial GSH levels and mitochondrial and cell damage. Oxidative stress as evaluated by mitochondrial damage and mortality can be prevented by treatment with GSH esters or ascorbate. There is apparent inkage between the antioxidant actions of GSH and ascorbate. This model, which may readily be applied to evaluation of the efficacy of other compounds in preventing oxidsative stress, offers an approach to study of other effects of GSH deficiency (e.g., on lipid metabolim, hematopoiesis), and closely resembles oxidative stress that occurs in certain human newborns and in other clinical states.Glutathione (GSH), the ubiquitous peptide thiol that provides cells with their reducing environment, is a key component of the antioxidant system (which includes ascorbate, a-tocopherol, and other compounds) that defends cells against the toxic effects ofoxygen (1-3). GSH is synthesized within cells; its export by many cells is a step in a recycling pathway that seems to protect cell membrane components against oxidative damage (4-6). The functions of GSH may be probed by examining the effects of decreasing cellular GSH. Cellular GSH may be decreased by administering compounds that react with GSH to form conjugates or that oxidize GSH to GSSG; however, these approaches are limited by lack of specificity of the reagents available and, because the effects obtained are transient, are associated with major perturbations of metabolism, or both. Inhibition of GSH synthesis by inhibition of -glutamylcysteine synthetase [rather than of GSH synthetase, whose blockage leads to metabolic acidosis (7,8)] is the preferred approach to a sustained decrease in cellular GSH (9). L-Buthionine-(S,R)-sulfoximine (BSO) and related sulfoximines are highly selective inactivators of -glutamylcysteine synthetase, and their administration to animals turns off cellular GSH synthesis effectively (10-13). BSO does not react with GSH, and there is no evidence that the sulfoximine moiety itself exerts toxicity, a conclusion supported by studies reported here on a diastereoisomer, L-buthionine-(R)-sulfoximine, that does not inhibit GSH synthesis. The effects observed after treatment with BSO, which ...

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“…Rowe and Strauss (15) found an increase in urine flow and solute excretion during the first 6 0 min in newborn piglets breathing 10% oxygen. Other investigators have reported that the newborn infant is oliguric during prolonged periods of respiratory distress (4,6,19). Possibly the increased urinary output observed early in the course of the stress is later modified by changes in total fluid and electrolyte balance as well as changes in renal hemodynamics.…”

Section: Discussionmentioning

confidence: 99%

Effects of Asphyxia on Renal Function in the Newborn Piglet

et al. 1978

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Summarveter was advanced into the abdominal aorta from the right femoral artery. This catheter was used for the determinatioiof This investigation was undertaken to determine the nature of blood pressure and heart rate and for sampling arterial blood. acute alterations in renal function following the production of Radioactive injections were made through a third h~~o x e m i a , h~~e r c a r b i a , and acidosis in newborn piglets 6-96 catheter (PE-90) placed in the ascending aorta by way of the left hr of age* After com~letion of the procedure piglets carotid artery. The urinary bladder was isolated through a small were allowed to recover from the effects of anesthesia. When midline abdominal incision and catheterizedThe posidead space was increased arterial Oxygen tion of all catheters was confirmed by inspection at the end of decreased whereas arterial carbon dioxide tension and hydrogen the experiment. ion concentration increased. There was little change in glomerAfter suturing the skin incisions all wounds were infiltrated ular fdtration rate. Total renal blood flow decreased and renal with lidocaine. Anesthesia was discontinued and the piglets were increased * 78 mm Hg/ placed upright in a supporting sling and allowed to recover from liter/mm/m2 to 1422 * 504). There was no change in distribu-anesthesia for hr. During the surgical procedure and the tion of intrarenal blood flow. Sodium excretion and urinary flow experiment the piglets were maintained at a body temperature rate demonstrated significant parallel increases following the of 380 using a Merco infant Under these conditions the increase in dead space. Plasma renin concentration increased animals remained calm and undisturbed in the sling, often from 67 to 110 ng/ml.sleeping during the experiment. Rectal temperature was continuously monitored using a Yellow Springs thermister. After Speculation completion of the surgical procedure the piglets were intubated Hypoxia, hypercarbia, and acidosis produced changes in renal with a 3.5 mm Portex endotracheal tube. Baseline determinafunction in newborn piglets. Therapeutic approaches to the tions were made and then a dead space 45 cc/ newborn human with respiratory distress must consider the kg) Was added to the tube in order to produce potential for modifications of renal function which may be hypoxia and hypercarbiadetrimental to the infant.Tritiated methoxy inulin (1 pCi/ml) was infused into the femoral vein at a rate of 0.04 ml/min beginning 1 hr before the onset of the experiment. During each clearance period urine The effects of respiratory distress on cardiopulmonary func-collections were made in preweighed flasks under oil. Urine tion in the newborn infant have been extensively studied. flow rate was estimated from the change in weight without However, renal function during this disease process has not ~0"ection for Specific gravity. Urine Was collected for determibeen adequately described. Recent observations have indicated nation of i n~l i n and sodium and potassium concentration. Artethat newbo...

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Renal failure following perinatal anoxia

Cited by 109 publications

References 12 publications

Prenatal Development of Antioxidant Enzymes in Rat Lung, Kidney, and Heart: Marked Increase in Immunoreactive Superoxide Dismutases, Glutathione Peroxidase, and Catalase in the Kidney

Prenatal Development of Antioxidant Enzymes in Rat Lung, Kidney, and Heart: Marked Increase in Immunoreactive Superoxide Dismutases, Glutathione Peroxidase, and Catalase in the Kidney

Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress.

Effects of Asphyxia on Renal Function in the Newborn Piglet

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