Disulfiram, as a candidate NF-kappa B and proteasome inhibitor, prevents endometriotic implant growing in a rat model of endometriosis

Abstract

OBJECTIVE: Disulfiram (DSF) exerts its therapeutic effects through oxidative, proteasome, and nuclear factor kappa beta (NF-kappa B) pathways. The study was planned to test the impact of DSF on growing of endometriotic implants in rats with experimentally induced endometriosis. PATIENTS AND METHODS: Thirty rats were labeled as the control (n = 8), sham (n = 6), GnRH-agonist (n = 8) and the DSF (n = 8) groups. The rats in the group 3 exposed to single dose leuprolide acetate. The rats in group 4 were treated with DSF for 21 days. The serum activity of oxidant and antioxidant markers, total oxidant status (TOS), total antioxidant status (TAS), interleukin-1 beta, and tumor necrosis factora (TNF-alpha) were determined. Implants were processed for NF-kappa B, PCNA, and CD34 immunostaining. RESULTS: The serum concentration of malondialdehyde in the DSF group was significantly higher than those in other groups. The concentration of TAS, TNF-alpha, and interleukin-1 beta in the DSF group considerably decreased compared to control group. Following treatment with DSF while the percentage of Grade 1 and 2 implants increased the percentage of Grade 3 and 4 implants decreased. The implants disappeared totally in two cases in the DSF group and one case in the GnRH-agonist group. The mean H-Scores of implant NF-kappa B and PCNA in DSF treated animals were found to significantly lower than those of the control group. CONCLUSIONS: By decreasing NF-kappa B expression, angiogenesis, and cell proliferation DSF prevents the growth of endometriotic implants.