Abstract
BackgroundBreast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. Despite evidence suggesting that renal proximal tubular epithelial cells participate in uric acid excretion in chickens, the roles of BCRP and MRP4 therein remain unclear. This study evaluated the relationship between BCRP and MRP4 expression and renal function in chickens.ResultsSixty laying hens were randomly divided into four treatment groups: a control group (NC) fed a basal diet; a sulfonamide-treated group (SD) fed the basal diet and supplemented with sulfamonomethoxine sodium via drinking water (8 mg/L); a fish meal group (FM) fed the basal diet supplemented with 16% fishmeal; and a uric acid injection group (IU) fed the basal diet and intraperitoneally injected with uric acid (250 mg/kg body weight). The results showed that serum uric acid, creatinine, and blood urea nitrogen levels were significantly higher in the SD and IU, but not FM, than in the NC groups. Renal tubular epithelial cells in the SD and IU groups were damaged. Liver BCRP and MRP4 mRNA and protein levels were significantly decreased in the SD and IU groups, but slightly increased in the FM group. In the SD group, BCRP and MRP4 were significantly increased in the ileum and slightly increased in the kidney. In the FM group, BCRP and MRP4 were significantly increased in the kidney and slightly increased in the ileum. In the IU group, BCRP and MRP4 were significantly increased in the kidney and ileum. BCRP and MRP4 expression in the jejunum was not affected by the treatments.ConclusionTogether, these results demonstrate that BCRP and MRP4 are involved in renal and intestinal uric acid excretion in chickens and that BCRP is positively related to MRP4 expression. Further, impairment of renal function results in an increase in serum uric acid as well as a compensatory increase in BCRP and MRP4 in the ileum; however, under normal renal function, renal BCRP and MRP4 are the main regulators of uric acid excretion.
Highlights
Breast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice
Impairment of renal function results in an increase in serum uric acid as well as a compensatory increase in BCRP and MRP4 in the ileum; under normal renal function, renal BCRP and MRP4 are the main regulators of uric acid excretion
Creatinine, and blood urea nitrogen (BUN) levels were significantly higher in the injection group (IU) group than in the NC group (P < 0.01); there were no significant differences between the fish meal group (FM) and NC groups
Summary
Breast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. In a study on uric acid metabolism in 65 patients with hyperuricemia, six patients (9.2%) exhibited an overproduction phenotype, 52 patients (80.0%) exhibited an underexcretion phenotype, and seven patients (10.8%) exhibited a mixed phenotype [5]. Uric acid excretion involves several uric acid transporters, such as breast cancer resistance protein (BCRP) [8], urate anion transporter 1 (URAT1) [9], multidrug resistance protein 4 (MRP4) [10], and organic anion transporters (OATs) [11]. Previous studies have demonstrated that active uric acid secretion occurs in chicken renal proximal tubular epithelial cells (cPTCs) and that this may involve multiple uric acid transporters [12]. Bataille et al [13] showed that in chickens, BCRP and MRP4 are expressed in cPTCs and
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