Oxalate transport by the mouse intestine in vitro is not affected by chronic challenges to systemic acid–base homeostasis

Abstract

In rats, we recently showed how a chronic metabolic acidosis simultaneously reduced urinary oxalate excretion and promoted oxalate secretion by the distal colon leading to the proposition that acid-base disturbances may trigger changes to renal and intestinal oxalate handling. The present study sought to reproduce and extend these observations using the mouse model, where the availability of targeted gene knockouts (KOs) would offer future opportunities to reveal some of the underlying transporters and mechanisms involved. Mice were provided with a sustained load of acid (NHCl), base (NaHCO) or the carbonic anhydrase inhibitor acetazolamide (ATZ) for 7 days after which time the impacts on urinary oxalate excretion and its transport by the intestine were evaluated. Mice consuming NHCl developed a metabolic acidosis but urinary oxalate was only reduced 46% and not statistically different from the control group, while provision of NaHCO provoked a significant 2.6-fold increase in oxalate excretion. For mice receiving ATZ, the rate of urinary oxalate excretion did not change significantly. Critically, none of these treatments altered the fluxes of oxalate (or chloride) across the distal ileum, cecum or distal colon. Hence, we were unable to produce the same effects of a metabolic acidosis in mice that we had previously found in rats, failing to find any evidence of the 'gut-kidney axis' influencing oxalate handling in response to various acid-base challenges. Despite the potential advantages offered by KO mice, this model species is not suitable for exploring how acid-base status regulates oxalate handling between the kidney and intestine.

Absence of the sulfate transporter SAT-1 has no impact on oxalate handling by mouse intestine and does not cause hyperoxaluria or hyperoxalemia

“…3). Again, this was consistent with our recent reports on the magnitude and direction of epithelial oxalate and sulfate transport by the mouse cecum (84,87), but the fluxes of both these anions were also entirely independent of SAT-1. Dawson et al (17) had previously shown a significant 47% reduction in oxalate uptake by BLMVs from the SAT-1-KO cecum in vitro, and in addition, the cecal contents of these KO Table 1.…”

“…2A) and a robust absorption of sulfate (Fig. 2B) under symmetrical, short-circuited conditions in vitro, in agreement with our recent reports of oxalate (85,87,88) and sulfate (86) fluxes by this segment. Unexpectedly, SAT-1 was not required to sustain the transport of either anion, contrary to the notion of SAT-1 as a SO 4 2Ϫ /oxalate exchanger facilitating intestinal oxalate secretion and sulfate absorption (58).…”

The role of NHE3 (Slc9a3) in oxalate and sodium transport by mouse intestine and regulation by cAMP

“…In the mouse distal ileum, oxalate transport has been shown to occur through the bicarbonate chloride exchangers, PAT1 (Slc26a6) and DRA (Slc26a3), contributing to secretion and absorption, respectively (Freel et al, 2006(Freel et al, , 2013. At least in other parts of the small intestine, PAT1 and DRA are known to be functionally and physically associated with NHE3 (Musch et al, 2009;Seidler & Nikolovska, 2019;Seidler et al, 2008;Singh et al, 2010;Walker et al, 2008;Xu et al, 2018); however, this study suggests NHE3 is not integral to the oxalate transport mechanism in murine distal ileum and basal oxalate fluxes were not dissimilar to what has previously been reported (Whittamore et al, , 2018Whittamore & Hatch, 2019). This occurred in the context of reduced G T in the NHE3 KO distal ileum.…”

Interaksi Molekuler Amonium Hidroksida

“…Jika napas sulit, berikan oksigen. Dapatkan bantuan medis (96,(193)(194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207)(208)(209)(210)(211) . Catatan dokter : Ssetelah paparan inhalasi, amati selama 24 s.d 72 jam sebagai edema paru mungkin tertunda…”