The Effect of Disulfiram in the Prevention of Postoperative Adhesion Formation in an Experimental Rat Uterine Horn Model.

ABSTRACT

Postoperative adhesions can cause serious complications, including intestinal obstruction, chronic abdominopelvic pain, and infertility in women. Here we investigate the effects of disulfiram on the postoperative adhesion model. Female Wistar rats were used (n = 72). The animals were separated into six groups (12 rats per group) group 1 (control), group 2 (300 mg/kg disulfiram administered for 3 days preoperatively), group 3 (50 mg/kg disulfiram administered for 3 days preoperatively and 14 days postoperatively), group 4 (300 mg/kg disulfiram administered for 3 days preoperatively and 14 days postoperatively), group 5 (50 mg/kg disulfiram administered 14 days postoperatively only), and group 6 (300 mg/kg disulfiram administered 14 days postoperatively only). A histopathologic examination was performed. Immunohistochemical stainings for matrix metalloproteinase-2 and 9 (MMP-2, and MMP-9) and vascular endothelial growth factor (VEGF) were evaluated. The macroscopic adhesion scores were significantly lower in the disulfiram groups (groups 3, 4, and 6) compared to the control group (p < 0.05). Inflammation scores were lower in all groups receiving disulfiram, but only reached statistical significance in group 4 (p < 0.05). In the immunohistochemical evaluation of the groups, MMP-9 was significantly lower in group 5 than group 4 (p < 0.05). There was no significant difference between the groups for MMP-2 and VEGF. We found that disulfiram reduced postoperative adhesion formation. Disulfiram becomes more effective (by directly reducing inflammation) when initiated during the preoperative period at high doses.