D ‐Malate decreases renal content of α‐ketoglutarate, a driving force of organic anion transporters OAT1 and OAT3, resulting in inhibited tubular secretion of phenolsulfonphthalein, in rats

In this study, we examined effects of D‐malate on the rat organic anion transport system. Uptake of 6‐carboxyfluorescein by HEK293 cells expressing rOAT1 or rOAT3 was not affected by D‐malate and L‐malate. Until 60 min after the intravenous injection of phenolsulfonphthalein (PSP), a typical substrate of the renal organic anion transporters, as a bolus to rats, 47.1% of the dose was recovered in the urine, and its renal clearance was estimated to be 8.60 ml/min/kg. D‐Malate but not L‐malate interfered with its renal excretion, resulting in the delayed elimination of PSP from plasma. No effect of D‐malate was recognized on creatinine clearance and expression level of rOAT3 in the kidney cortex. D‐Malate increased plasma concentration of α‐ketoglutarate. And, the compound extremely stimulated the renal excretion of α‐ketoglutarate, implying that D‐malate inhibited its reabsorption. The content of α‐ketoglutarate was significantly decreased in the kidney cortex of rats administered D‐malate. Collectively, this study represents that D‐malate abrogates the tubular secretion of PSP, and the reduction of the renal content of α‐ketoglutarate was proposed to be one of the mechanisms. And, we suggest the relationship between the reabsorption of α‐ketoglutarate and the basolateral uptake of organic anion in the kidney.
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL PAPER Source Type: research