Stimulation of weak organic acid uptake in rat renal tubules by cadmium and nystatin

Nikiforov, A. A.; Ostretsova, Irina B.

doi:10.1016/0006-2952(94)90481-2

Cited by 10 publications

(3 citation statements)

References 18 publications

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“…Similar results were obtained when we studied the influence of Cd on the fluorescein uptake and gluconeogenesis in rat RPTs (Nikiforov & Ostretsova, 1994). Then we tested one more agent inducing in vivo a Fanconi's syndrome, namely maleate, and found that maleate (0O1-1 mM) also stimulated the baseline fluorescein uptake in standard (but not Na-free) medium.…”

supporting

confidence: 76%

Epithelia & Membrane Transport

1994

The Journal of Physiology

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supporting

confidence: 76%

Epithelia & Membrane Transport

1994

The Journal of Physiology

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“…To further confirm this point, two TCA enzyme inhibitors, malonate and fluoroacetate, were tested using CÜ cells. A 20 min pretreatment of the cells with 10 mÒ malonate (Table 2; Nikiforov & Ostretsova, 1994) or 1 mÒ fluoroacetate (Table 2; Nikiforov & Ostretsova, 1994) had no effect on the subsequent HµOµ-induced acidosis, again suggesting that the respiratory chain and TCA cycle are not involved in HµOµ-induced acidosis in CÜ cells.…”

Section: Cü Glioma Cells: Inhibition Of the Glycolytic Pathwaymentioning

confidence: 95%

Mechanism of oxidative stress‐induced intracellular acidosis in rat cerebellar astrocytes and C₆ glioma cells

Tsai

Wang

Chen

et al. 1997

The Journal of Physiology

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Following ischaemic reperfusion, large amounts of superoxide anion (.O2−), hydroxyl radical (.OH) and H2O2 are produced, resulting in brain oedema and changes in cerebral vascular permeability. We have found that H2O2 (100 μm) induces a significant intracellular acidosis in both cultured rat cerebellar astrocytes (0.37 ± 0.04 pH units) and C6 glioma cells (0.33 ± 0.07 pH units). Two membrane‐crossing ferrous iron chelators, phenanthroline and deferoxamine, almost completely inhibited H2O2‐induced intracellular acidosis, while the non‐membrane‐crossing iron chelator apo‐transferrin had no effect. Furthermore, the acidosis was completely inhibited by two potent membrane‐crossing .OH scavengers, N‐(2‐mercaptopropionyl)‐grycine (N‐MPG) and dimethyl thiourea (DMTU). Since .OH can be produced during iron‐catalysed H2O2 breakdown (Fenton reaction), we have shown that a large reduction in pH1 in glial cells can result from the production of intracellular .OH via H2O2 oxidation. We have ruled out the possible involvement of: (i) an increase in intracellular Ca2+ levels; and (ii) inhibition of oxidative phosphorylation. Our results suggest that .OH inhibits glycolysis, leading to ATP hydrolysis and intracellular acidosis. This conclusion is based on the following observations: (i) in glucose‐free medium, or in the presence of iodoacetate or 2‐deoxy‐D‐glucose, H2O2‐induced acidosis is completely suppressed; (ii) H2O2 and iodoacetate both produce an increase in levels of intracellular free Mg2+, an indicator of ATP breakdown; and (iii) direct measurement of intracellular ATP levels and lactate production show 50 and 55% reductions in ATP content and lactate production, respectively, following treatment with 100 μm H2O2. Inhibition of the pH1 regulators (i.e. the Na+–H+ exchange and possibly the Na+–HCO3−–dependent pH1 transporters) resulting from H2O2‐induced intracellular ATP reduction may also be involved in the H2O2‐evoked intracellular acidosis in glial cells.

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“…The most reasonable explanation is stimulation of the tricarboxylic acid cycle by Cd 2+ , resulting in an enhanced delivery of ␣-ketoglutarate. 20 In summary, the data presented provide evidence that divalent inorganic cations inhibit renal PAH transport probably by their calcium antagonistic properties and/or inhibition of renal Na + /H + -ATPase. Furthermore, direct toxic effects may contribute to the reduced PAH transport observed after Ni 2+ and Zn 2+ application.…”

Section: Discussionmentioning

confidence: 71%

Effects of inorganic divalent cations on the renal basolateral transport system for organic anions

Hohage¹,

Matzkies

Mergelsberg

et al. 1999

J. Appl. Toxicol.

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Recent work demonstrated that the heavy metal ion Cd2+ increases the transport of p ‐aminohippuric acid (PAH) across the basolateral membrane of microdissected non‐perfused rabbit kidney S2 proximal tubule segments. Usually, such ions induce damage of various renal transport systems, therefore the effects of divalent metal ions Zn2+, Co2+ and Ni2+ on this transporter were investigated. Addition of Ni2+ or Zn2+ to the bathing solution leads to a significant reduction of basolateral PAH transport, with ic50 values of 2 × 10−5 and 10−6 M, respectively, whereas Co2+ failed to inhibit PAH accumulation. Simultaneous incubation with thrombin (10−9 M), which is known to increase [Ca2+]i, abolished the effects of the divalent ions. Our results indicate that Ni2+ and Zn2+ reduce cellular PAH uptake. Because Ni2+ and Zn2+ are calcium channel blockers, these effects are probably due to a reduction of [Ca2+]i by an interaction of these metals with binding sites in the calcium channel, whereas Co2+ does not affect these binding sites. This finding is supported by the fact that thrombin abolished the cation effects. Copyright © 1999 John Wiley & Sons, Ltd.

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Stimulation of weak organic acid uptake in rat renal tubules by cadmium and nystatin

Cited by 10 publications

References 18 publications

Epithelia & Membrane Transport

Epithelia & Membrane Transport

Mechanism of oxidative stress‐induced intracellular acidosis in rat cerebellar astrocytes and C₆ glioma cells

Effects of inorganic divalent cations on the renal basolateral transport system for organic anions

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Stimulation of weak organic acid uptake in rat renal tubules by cadmium and nystatin

Cited by 10 publications

References 18 publications

Epithelia & Membrane Transport

Epithelia & Membrane Transport

Mechanism of oxidative stress‐induced intracellular acidosis in rat cerebellar astrocytes and C6 glioma cells

Effects of inorganic divalent cations on the renal basolateral transport system for organic anions

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Resources

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Mechanism of oxidative stress‐induced intracellular acidosis in rat cerebellar astrocytes and C₆ glioma cells