Alpha-mangostin counteracts hyperuricemia and renal dysfunction by inhibiting URAT1 renal transporter in insulin resistance rat model

Abstract

BackgroundAlpha-mangostin (AM) has been shown to have hypoglycemic activity. This study aimed to analyze the effects of AM at a dose of 100 mg/kg and 200 mg/kg to alleviate hyperuricemia and renal dysfunction on high-fat/high-glucose diet and low dose streptozotocin (HF/HG/STZ) injection-induced IR rat model. IR was induced in male Wistar rats by giving a HF/HG diet for 11 weeks and single injection of STZ (35 mg/kg, i.p.), then divided randomly into IR rats, IR rats treated with AM 100 and 200 mg/kgBW given by gavage for 8 weeks. At the end of the 11th week, all rats were killed, and the kidneys were taken to be analyzed for urate transporters 1 (URAT1) and glucose transporters 9 (GLUT9). We also assessed serum uric acid, proteinuria, BUN, creatinine clearance, HOMA-IR, and fasting blood glucose (FBG).ResultsWe have found the significant increase in HOMA-IR and FBG levels of the IR rats, in comparison with its control groups, which were decreased significantly after AM administration at both doses. URAT1 and GLUT9 mRNA and protein expressions in kidney in the IR + AM at both doses groups also decreased compared those in the IR without treatment group, though the decrease in GLUT9 did not appear to be statistically significant. Consequently, hyperuricemia and renal dysfunction were attenuated by AM treatment at both doses.ConclusionAfter considering all findings, AM might be a potential candidate to ameliorate IR-induced hyperuricemia and renal dysfunction at least in part by modulating the renal URAT1.