Curcumin attenuates renal ischemia reperfusion injury in mice by inhibiting the activation of toll-like receptor 4 signaling

Objective To investigate the protective effect of curcumin on renal ischemia reperfusion (IR) injury and its related mechanism in mice. Methods C57BL/6 mice were randomly divided into 4 groups: sham-operated (SO) group, low-dose and high-dose curcumin (CM-L and CM-H) groups (the mice were injected with 5mg/kg or 20mg/kg curcumin just before ischemia induction.) and control group (the mice were injected with equal volume of physiological saline at the same time.). At a 6-hour reperfusion, the serum and renal samples were collected. The serum creatinine (Scr) and blood urea nitrogen (BUN) levels in serum were determined and renal patho-histological changes were also examined. Expressions of Toll-like receptor 4 (TLR-4), high mobility group protein B1 (HMGB1), hyaluronan (HA), hyaluronan synthase (HAS) 1, HAS2, HAS3 and interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and TLR-4 protein were assessed using quantitative fluorescence RT-PCR and Western blotting. The infiltration of F4/80-positive macrophage cells was detected using immunohistochemical analysis and the IL-6 and TNF-α levels in serum were determined by enzyme linked immunosorbent assay (ELISA). Results Compared with control group, CM-L and CM-H group exhibited lower levels of Scr and BUN (Scr: Control 235.4±28.7, CM-L 167.8±17.2, CM-H 125.8±13.3μmol/ L; BUN: Control 21.6±2.7, CM-L 18.1±2.4, CM-H 12.5±1.7mmol/L; P < 0.05 or P < 0.01), less pathological changes ( Jablonski scores: Control 2.15±0.28, CM-L 1.72±0.21, CM-H 1.42±0.15; P < 0.01), lower mRNA levels of TLR-4, HMGB1, HA, HAS1, HAS2, HAS3, IL-6 and TNF-α, lower levels of TLR-4 protein and HMGB1, less infiltration of macrophage [Control 32.4±4.2/high power field (HPF), CM-L 24.8±3.6/HPF, CM-H 18.9±3.1/HPF; P < 0.01]. Moreover, the serum levels of IL-6 and TNF-α were lower in CM-L and CM-H groups than those in control group (IL-6: Control 1411.2±150.6, CM-L 918.7±113.4, CM-H 809.6±108.3pg/ ml; TNF-α: Control 154.7±21.1, CM-L 135.8±15.2, CM-H 125.6±14.6pg/ml; P < 0.05 or P < 0.01). Conclusion Curcumin can ameliorate renal IR injury in mice, which is attributable to inhibition of the activation of Toll-like receptor 4 signaling.