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- W53100660 abstract "We studied the effect of RGZ treatment on urinary ammonium and citrate excretion as noninvasive indices of proximal tubular cell pH. Male Sprague Dawley rats fed RGZ 9.4mg/kg diet for 3 days increased their ammonium excretion by 120%(42.6± 3 vs 19.4 ±2umol/mg, p=0.01) and decreased their citrate excretion by 66%(5.8 ± 0.9 vs 17.4± 4.7 mg/mg creatinine, p=0.03) as urine pH decreased (6.16± 0.06 vs 6.33± 0.07, p=0.04). Serum bicarbonate remained unchanged (27 ± 1 and 27±1mM) suggesting enhanced systemic metabolic acid production. In a healthy human subject, RGZ, 6mg x 2days increased UV NH4+ by 186%(33 vs 17umol/min, avg of 3-1h clearance periods), decreased urine pH (5.7 vs 6.4) and increased plasma bicarbonate(24.8 to 28.1mM). In proximal tubule-like OKP cells RGZ (20uM) induced a spontaneous acidosis (6.98± 0.03 vs 7.29± 0.05, p=0.01 after 8minutes measured by BCECF assay) and increased ammonium production from glutamine by 176%(2,421± 147 vs 1,376± 67 nmol/mg protein/18h, p<0.005). Since NHE 3 protein increased 50% and sodium excretion decreased (2JPET 308:426,2004), these results are consonant with increased NH4+/Na+ exchange contributing to sodium retention observed with RGZ and that either cellular acidosis or PPARγ upregulating NHE3 activity in the proximal tubule." @default.
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- W53100660 date "2006-03-01" @default.
- W53100660 modified "2023-09-27" @default.
- W53100660 title "Rosiglitazone induces renal cellular acidosis." @default.
- W53100660 doi "https://doi.org/10.1096/fasebj.20.5.a1223-c" @default.
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