Na+,K+-ATPase Expression in Maleic-Acid-Induced Fanconi Syndrome in Rats

Abstract

Na+,K(+)-ATPase activity and its alpha 1 subunit protein and mRNA in kidney cortex were monitored in rats developing Fanconi syndrome after the administration of maleate. Na+,K(+)-ATPase activity was significantly lower than in saline-injected controls, although this was partially mediated by a general, non-specific decrease in the cortex protein content. 2. The low activity of the sodium pump correlated with low abundance of alpha 1 subunit mRNA and protein levels. Hsp60 protein levels were also decreased in kidney cortex from maleate-treated rats. 3. Kidney cortex brush-border membrane vesicles from maleate-treated rats showed a marked decrease in Na(+)-dependent alanine and glucose transport, which was not dependent on the Na(+)-transmembrane gradient itself, a finding which is consistent with a more stable effect at the plasma membrane level. 4. The effect of maleate may be partially non-specific and involve a great variety of proteins, but seems to be restricted to selected tissues because alpha 1 subunit Na+,K(+)-ATPase and hsp60 protein amounts were not significantly modified in livers from rats developing Fanconi syndrome. 5. These results show that maleate administration induces a low activity of selected concentrative transport systems and a decrease in Na+,K(+)-ATPase activity and expression. The combination of both effects may explain the increased excretion of most organic solutes present in rats developing Fanconi syndrome.

Melatonin attenuates ifosfamide‐induced Fanconi syndrome in rats

“…Most solute transport, including bicarbonate, phosphate, amino acids, and glucose, is mediated by Na + ‐coupled mechanisms. The effectiveness of Na + ‐dependent transport depends on the maintenance of a low intracellular sodium concentration, and the basolateral Na + ,K + ‐ATPase plays the major role in maintaining this process [7, 8, 45]. The failure of proximal sodium transport, that leads to a global failure in reabsorption, has been shown in an experimental model of FS induced by maleic acid [8, 45].…”

“…However, the clinical efficacy of IFO is greatly limited because of its severe cytotoxic side effects including hemorrhagic cytitis and nephrotoxicity [6]. Proximal tubular impairment is the most common feature of toxicity, which frequently presents as Fanconi syndrome (FS) with a generalized increase in organic solute and ion excretion resulting in polyuria, glucosuria, aminoaciduria, proteinuria, calciuria and phosphaturia [7, 8], these changes are a result of a number of reabsorptive and secretory transport defects, mainly of Na + ‐dependent transporters.…”

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

“…Published work reported that exposure to high doses of MA result in phenotypic manifestations such as alopecia and significant decreases in both absolute and relative organ weights (Burnett et al, ). Upon consumption, the absorbed and metabolized MA become nephrotoxic and cause symptoms such as phosphaturia, glycosuria, low molecular weight proteinuria, metabolic acidosis and aminoaciduria (Castano, Marzabal, Casado, Felipe, & Pastor‐Anglada, ; Shikano et al, ). The aforementioned damages to the proximal renal tubules of the kidney, collectively known as Fanconi syndrome, can result in cell necrosis and renal tubular injury in the proximal tubules (Bunton, Fuller, Perry, & Shiner, ).…”

Proteomic analysis of rat kidney under maleic acid treatment by SWATH‐MS technology

“…At present, a wide range of past studies have already indicated that the consumption of maleic acid can cause kidney damage . However, most of those studies discussed the damage caused to renal tubules.…”