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[Curcumin reduces paraquat-induced oxidative injury in A549 cells by activation of the Nrf2-ARE pathway].

OBJECTIVE
To investigate the protective effect of curcumin (CU) on type II alveolar epithelial cells (A549 cells) during paraquat (PQ)-induced oxidative damage and its underlying mechanism.


METHODS
Routinely cultured A549 cells were divided into blank control group, CU control group, PQ group, and PQ+Cu group to receive respective treatments for 24 h. Cell viability was determined by MTT assay. The NFE2L2 expression in A549 cells was measured by RT-PCR and Western blot. The activities of the heme oxygenase-1 (HO-1) and NAD (P) H: quinone oxidoreductase 1 (NQO-1) in cells and the superoxide dismutase (SOD) and catalase (CAT) in supernatant, as well as malondialdehyde (MDA) content, were measured by enzyme-linked immunosorbent assay. After siRNA depletion of Nrf2, the protective effect of CU on A549 cells during PQ-induced oxidative damage was evaluated.


RESULTS
PQ, even at a dose of 0.1 mmol/L, could significantly suppress the viability of A549 cells in a dose-dependent manner. CU showed no significant inhibitory effect on the viability of A549 cells when given at a dose below 160 ümol/L. Compared with the blank control group, the PQ group had significantly decreased SOD activity and significantly increased CAT activity and MDA content after 24-h exposure to 800 ümol/L PQ (P < 0.05 or P < 0.01). Thanks to pretreatment with 80 ümol/L CU, the PQ+CU group had significantly increased SOD and CAT activities and significantly decreased MDA content compared with the PQ group (P < 0.01). Compared with the blank control group, the PQ group had significantly increased expression of NFE2L2 and its downstream factors HO-1 and NQO-1 (P < 0.01), while the PQ+CU group had significantly higher expression of NFE2L2, HO-1,and NQO-1 than the PQ group (P < 0.01).Compared with the PQ+CU group, the CU+PQ+NFE2L2siRNA group had significantly decreased SOD and CAT activities and significantly increased MDA content (P < 0.01).


CONCLUSION
Low-dose CU significantly reduces the PQ-induced oxidative damage in A549 cells in vitro by activation of the Nrf2-ARE pathway.