Tumor necrosis factor-α induced protein 6 attenuates acute kidney injury following paraquat poisoning in rats

Abstract

To explore the effects of tumor necrosis factor-α induced protein 6 (TSG-6) on acute kidney injury (AKI) following paraquat poisoning in rats. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into sham group (n=8), model group (n=8) and TSG-6-treated group (n=8) using a randomized number table. Rats were given an injection of 50 mg/kg of paraquat intraperitoneally (total volume was equalled to sterile normal saline) in model and TSG-6-treated groups. Rats in sham group were given 2 mg/kg of sterile saline. After 1 hour of paraquat administration, rats were treated with 30 μg of recombinant human TSG-6 intraperitoneally in TSG-6-treated group. After 6 hours of paraquat administration, serum was collected to assess renal function, then rats were sacrificed and renal tissues were immediately harvested. AKI score was evaluated by renal histopathology and gene expression of pro-inflammatory cytokines including interleukins (IL-1β and IL-6) and tumor necrosis factor-α (TNF-α) in kidney was assayed with real-time reverse transcription-polymerase chain reaction (RT-PCR). Compared with sham group, blood urea nitrogen (BUN), creatinine (Cr) and AKI score were significantly increased in model group (BUN: 22.64 ± 2.36 mmol/L vs. 7.09 ± 0.65 mmol/L, t=6.986, P=0.000; Cr: 177.28 ± 18.67 μmol/L vs. 60.32 ± 3.11 μmol/L, t=7.134, P=0.000; AKI score: 9.14 ± 0.28 vs. 0.30 ± 0.23, t=9.013, P=0.000). Moreover, the mRNA expressions of IL-1β, IL-6 and TNF-α were significantly elevated in model group (IL-1β mRNA: 3.23±0.28 vs. 1.00 ± 0.07, t=5.874, P=0.000; IL-6 mRNA: 4.16 ± 0.37 vs. 1.00 ± 0.08, t=7.125, P=0.000; TNF-α mRNA: 3.85 ± 0.31 vs. 1.00 ± 0.10, t=6.342, P=0.000). However, serum BUN, Cr, AKI score and the mRNA expressions of IL-1β, IL-6 and TNF-α in TSG-6-treated group were significantly lower than those in model group (BUN: 14.07 ± 5.23 mmol/L vs. 22.64 ± 2.36 mmol/L, t=2.533, P=0.026; Cr: 112.76 ± 14.81 μmol/L vs. 177.28 ± 18.67 μmol/L, t=2.778, P=0.016; AKI score: 5.35 ± 0.19 vs. 9.14 ± 0.28, t=2.885, P=0.013; IL-1β mRNA: 2.26 ± 0.19 vs. 3.23 ± 0.28, t=2.457, P=0.023; IL-6 mRNA: 2.92±0.29 vs. 4.16 ± 0.37, t=2.975, P=0.011; TNF-α mRNA: 2.58 ± 0.23 vs. 3.85 ± 0.31, t=2.564, P=0.019). TSG-6 attenuates AKI following paraquat poisoning by suppressing inflammatory response.