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

OBJECTIVE Disulfiram (DSF) exerts its therapeutic effects through oxidative, proteasome, and nuclear factor kappa beta (NF-κB) 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-1β, and tumor necrosis factor-α (TNF-α) were determined. Implants were processed for NF-κB, 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-α, and interleukin-1β 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-κB and PCNA in DSF treated animals were found to significantly lower than those of the control group. CONCLUSIONS By decreasing NF-κB expression, angiogenesis, and cell proliferation DSF prevents the growth of endometriotic implants.