Effects of sulforaphane on oxidative damage and expression of apurinic/apyrimidinic endonuclease 1 in rats with acute lung injury induced by sepsis

Abstract

Objective To evaluate the effects of sulforaphane on oxidative stress injury and apurinic/apyrimidinic endonuclease 1 (APE1) expression in rats with acute lung injury induced by sepsis. Methods Sixty Sprague-Dawley rats were divided into three groups according to the random number table: the sham operation group, the model group and the treatment group with 20 rats in each group. In the sham operation group, only laparotomy and abdominal operation were performed, while rat sepsis models were prepared by cecal ligation and puncture (CLP) in the model and the treatment groups. Rats in the treatment group were given intraperitoneal injection of 50 mg/kg sulforaphane immediately after operation, and the remaining two groups were injected with equal normal saline. The arterial blood samples were collected from the right common carotid artery at 24 h after operation; then the lung tissues were taken out after the rats were sacrificed. The pathological results were observed under light microscope and the wet/dry ratio of lung tissues was measured. Meanwhile, the expressions of superoxide dismutase (SOD) and glutathione (GSH) in lung homogenates were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of APE1 in lung tissues was examined by Western-blotting. Results Hematoxylin-eosin (HE) staining showed that the lung tissues of the sham operation group were structurally clear with no obvious edema and inflammatory cell infiltration, the pathological changes in the model group were serious, and the lung injury was less in the treatment group than in the model group. There were significant differences in the wet/dry ratio (3.49 ± 0.26, 5.56 ± 0.20, 4.96 ± 0.15), arterial oxygenation index (453 ± 23, 232 ± 22, 332 ± 11), GSH expression [(8.57 ± 0.26), (4.36 ± 0.08), (6.23 ± 0.20) mg/g] and SOD expression [(91.0 ± 3.0), (55.5 ± 2.5), (72.1 ± 2.4) NU/mg] among the three groups (F = 107.897, 128.676, 275.863, 183.797; all P < 0.001). The wet/dry ratio was significantly higher in the model and the treatment groups than in the sham operation group (all P < 0.05), while it was significantly lower in the treatment group than in the model group (P < 0.05). Compared with the sham operation group, the oxygenation index, GSH and SOD decreased significantly in the other two groups (all P < 0.05), while these factors were significantly higher in the treatment group than in the model group (all P < 0.05). Western-blotting showed that the expression of APE1 in lung tissues changed significantly in all three groups (F = 453.991, P < 0.001). It decreased more significantly in the model and treatment groups than in the sham operation group (all P < 0.05), while it was significantly higher in the treatment group than in the model group (P < 0.05). Conclusion Sulforaphane can alleviate acute lung injury in septic rats, and its mechanism may be related to the improvement of oxidative stress response and up regulation of APE1 expression in lung tissues. Key words: Sulforaphane; Acute lung injury; Sepsis; Oxidative stress; Apurinic/apyrimidinic endonuclease 1