Protective Effects of Curcumin against Sodium Arsenite-induced Ovarian Oxidative Injury in a Mouse Model.

BACKGROUND: Excessive reactive oxygen species (ROS) may lead to a number of reproductive diseases such as polycystic ovary syndrome. This study aimed to establish an animal model of ovarian oxidative stress and to assess the protective effect of curcumin against oxidative injury.

METHODS: Ovarian oxidative stress was induced in female Kunming mice (n = 40) with intraperitoneal injection of 8 mg/kg sodium arsenite (As) once every other day for 16 days; meanwhile, they were, respectively, treated by intragastric administration of 0, 100, 150, or 200 mg/kg (n = 10/group) curcumin once per day for 21 days. Ten normal mice were used as control. Then, the mice were injected intraperitoneally with BrdU and sacrificed; the right ovaries were collected for hematoxylin and eosin (HE) staining and BrdU immunohistochemistry, and the left ovaries for enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses.

RESULTS: The ELISA results showed that ROS (11.74 ± 0.65 IU/mg in 8 mg/kg AS + 0 mg/kg curcumin group vs. 10.71 ± 0.91 IU/mg in control group, P= 0.021) and malondialdehyde (MDA) (0.32 ± 0.02 nmol/g in 8 mg/kg AS + 0 mg/kg curcumin group vs. 0.27 ± 0.02 nmol/g in control group, P= 0.048) increased while superoxide dismutase (SOD) (3.96 ± 0.36 U/mg in 8 mg/kg AS + 0 mg/kg curcumin group vs. 4.51 ± 0.70 U/mg in control group, P= 0.012) and glutathione peroxidase (17.36 ± 1.63 U/g in 8 mg/kg AS + 0 mg/kg curcumin group vs. 18.92 ± 1.80 U/g in control group, P= 0.045) decreased in the ovary after injection of As, indicating successful modeling of oxidative stress. Curcumin treatment could considerably increase SOD (4.57 ± 0.68, 4.49 ± 0.27, and 4.56 ± 0.25 U/mg in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, allP < 0.05) while significantly reduce ROS (10.64 ± 1.38, 10.73 ± 0.71, and 10.67 ± 1.38 IU/mg in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, allP < 0.05) and MDA (0.28 ± 0.02, 0.25 ± 0.03, and 0.27 ± 0.04 nmol/g in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively; bothP < 0.05) in the ovary. HE staining and BrdU immunohistochemistry of the ovarian tissues indicated the increased amount of atretic follicles (5.67 ± 0.81, 5.84 ± 0.98, and 5.72 ± 0.84 in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, all P < 0.05), and the inhibited proliferation of granular cells under oxidative stress would be reversed by curcumin. Furthermore, the Western blotting of ovarian tissues showed that the p66Shc expression upregulated under oxidative stress would be lowered by curcumin.

CONCLUSION: Curcumin could alleviate arsenic-induced ovarian oxidative injury to a certain extent.