To explore the effect and potential mechanism of hyperuricemia (HUA) on acetaminophen (APAP)-induced liver injury.

Male mice were randomly divided into four groups: group A (control), group B [establishment of a hyperuricemia (HUA) model], group C (administered by oral gavage at a dose of 300 mg·kg^-1 APAP), and group D (establishment of a HUA model combined with administered by oral gavage at a dose of 300 mg·kg^-1 APAP). The HUA model was established by intraperitoneal injection of potassium oxonate (350 mg·kg^-1) and gavage of xanthine (450 mg·kg^-1) for 14 consecutive days. On day 13, mice in group C and group D received APAP via gavage. All mice were sacrificed 24 h later. Serum levels of uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by biochemical analyzer. Liver histopathology was evaluated by hematoxylin-eosin (H&E) staining. Levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in liver tissues were measured using commercial kits. Immunofluorescence was used to detect the relative expression of nuclear factor erythroid 2-related factor 2 (Nrf2).

The serum uric acid levels in the group A, group B, group C and group D were (186.20±15.61), (521.50±56.81), (325.20±31.74) and (682.00±49.51) μmol·L^-1, respectively; the liver coefficients were (4.51±0.14)%, (4.77±0.23)%, (4.98±0.21)%, and (5.51±0.30)%, respectively; the serum ALT levels were (55.80±15.86), (78.09±10.92), (27 688.81±7 166.01), and (34 571.89±7 793.74) U·L^-1, respectively; the AST levels were (159.90±29.72), (143.70±26.46), (10 880.00±4 291.01), and (19 824.84±7 874.64) U·L^-1, respectively; the hepatic MDA contents were (5.42±0.38), (7.77±0.32), (6.07±0.31), and (9.08±0.36) mol·g^-1·prot^-1, respectively; the ROS contents were (28.09±3.52), (39.67±2.70), (32.22±4.71), and (45.67±2.71) μg·g^-1·prot^-1, respectively; the GSH levels were (2.47±0.27), (1.72±0.16), (2.24±0.16), and (1.37±0.11) μg·g^-1·prot^-1, respectively; the IL-1β contents were (22.16±0.88), (31.74±1.82), (25.35±1.07), and (38.82±1.68) μg·g^-1·prot^-1, respectively; the TNF-α contents were (114.90±10.60), (180.20±3.72), (142.20±4.69), and (228.10±17.33) μg·g^-1·prot^-1, respectively; the relative protein expression of Nrf2 were 218.30±5.16, 63.60±29.02, 100.80±23.60, and 9.31±8.83, respectively. The indices in groups B and C were significantly different from those in group A, and the indices in group D were significantly different from those in group C, with all differences showing statistical significance (P<0.05).

In the hyperuricemia (HUA) mouse model, the liver damage induced by acetaminophen (APAP) is aggravated, and this effect may be related to the downregulation of NRF2 expression.