Sanghuangporus vaninii ethanol extract alleviates hyperuricemic renal injury by regulating the uric acid transporters and inhibiting HK-2 apoptosis

To investigate the acute toxicity of Sanghuangporus ethanol extract (SHEE) on ICR mice and the underlying mechanism of anti-hyperuricemic renal injury. Materials and

Overall, an oral dose of SHEE below 2500 mg/kg is safe. SHEE inhibits HUA-induced kidney injury by regulating the UA transporters URAT1, GLUT9, OAT1, OAT3 and ABCG2 and inhibiting HK-2 apoptosis.

ICR mice were given a single gavage of 1250, 2500, and 5000 mg/kg SHEE, and the general behavior, mortality, body weight, dietary, and water intake were evaluated within 14 days to determine the acute toxicity level. The hyperuricemic kidney injury model in ICR mice was induced with potassium oxonate (PO) and adenine, and the mice were subsequently treated with SHEE (125, 250, 500 mg/kg). HE and hexamine silver staining (PASM) were used to observe the pathology of the kidney. Biochemical markers were tested by uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), xanthine oxidase (XOD), alanine transferase (ALT), and aspartate transaminase (AST) kits. An MTT assay was used to measure the effects of SHEE on the proliferation of HK-2 damaged by UA. Western blotting and RT-PCR were used to determine the expression of Bcl-2 family-related proteins and major UA transporters, including URAT1, GLUT9, OAT1, OAT3, and ABCG2, respectively.

Firstly, the acute toxicity study data showed that the median lethal dose (LD50) of SHEE was above 5000 mg/kg, and its oral administration was nontoxic at 2500 mg/kg and below. In addition, SHEE alleviated HUA and its renal injury in ICR mice. SHEE reduced the contents of UA, Cr, BUN and XOD in blood and the contents of ALT and AST in the liver. Furthermore, SHEE inhibited the expression of URAT1 and GLUT9 and promoted the expression of OAT1, OAT3, and ABCG2. More importantly, SHEE could downregulate the apoptosis level and caspase-3 activity. Conclusions: Overall, an oral dose of SHEE below 2500 mg/kg is safe. SHEE inhibits HUA-induced kidney injury by regulating the UA transporters URAT1, GLUT9, OAT1, OAT3 and ABCG2 and inhibiting HK-2 apoptosis.