Nephroprotective Effect of Functional Beverage of Dolichous Biflorus Seeds on Ethylene Glycol Induced Urolithiasis: A Mechanistic Approach

Calcium oxalate is the most common type of urolithiasis and is suggested due to membrane oxalate transporters dysfunction. This study has used Dolichos biflorus seeds as a functional beverage to explore its bioactive substances’ role on membrane transporters for managing urolithiasis. Urolithiasis model of ethylene glycol induced calcium oxalate crystals in albino Wistar rats was used in this study. Treatment of functional beverage of Dolichos biflorus seeds restored normal blood and urinary oxalate and citrate level and showed anti-urolithiasis activity. Probenecid, a membrane organic anion transporter (Slc26) inhibitor, treatment has abolished anti-urolithiasis activity of functional beverage and suggested Dolichos biflorus produce effect through the restoration of membrane oxalate transporters activity. An oxalate-less diet did not significantly reduce urinary, and plasma oxalate in probenecid treated animals and suggested that dietary oxalate is not primarily involved in calcium oxalate urolithiasis and conditions like hyperoxalemia and hyperoxaluria. Therefore, our findings suggested that endogenous oxalate in conjunction with idiopathic or chronic reduced activity or defective Slc26 transporters due to aging results in calcium oxalate kidney stones. The functional beverage of Dolichos biflorus seeds exhibited anti-urolithiasis activity through improving the activity of Slc26 transporters.

Enteric Oxalate Secretion Mediated by Slc26a6 Defends against Hyperoxalemia in Murine Models of Chronic Kidney Disease

BackgroundA state of oxalate homeostasis is maintained in patients with healthy kidney function. However, as GFR declines, plasma oxalate (Pox) concentrations start to rise. Several groups of researchers have described augmentation of oxalate secretion in the colon in models of CKD, but the oxalate transporters remain unidentified. The oxalate transporter Slc26a6 is a candidate for contributing to the extrarenal clearance of oxalate via the gut in CKD.MethodsFeeding a diet high in soluble oxalate or weekly injections of aristolochic acid induced CKD in age- and sex-matched wild-type and Slc26a6−/− mice. qPCR, immunohistochemistry, and western blot analysis assessed intestinal Slc26a6 expression. An oxalate oxidase assay measured fecal and Pox concentrations.ResultsFecal oxalate excretion was enhanced in wild-type mice with CKD. This increase was abrogated in Slc26a6−/− mice associated with a significant elevation in plasma oxalate concentration. Slc26a6 mRNA and protein expression were greatly increased in the intestine of mice with CKD. Raising Pox without inducing kidney injury did not alter intestinal Slc26a6 expression, suggesting that changes associated with CKD regulate transporter expression rather than elevations in Pox.ConclusionsSlc26a6-mediated enteric oxalate secretion is critical in decreasing the body burden of oxalate in murine CKD models. Future studies are needed to address whether similar mechanisms contribute to intestinal oxalate elimination in humans to enhance extrarenal oxalate clearance.