The effects of levamisole on experimental endometriosis: a randomized controlled trial in a rat model

Abstract

Purpose: To assess the effects of levamisole on experimental endometriosis in rats through the histopathology of the implants, the blood leukocyte and lymphocyte counts and the concentrations of interleukin-6, vascular endothelial growth factor-A and tumor necrosis factor-alpha in the peritoneal environment at the three healthy, endometriotic and post-treatment milestones.

Methods: Twenty-two 8-week-old Sprague-Dawley rats with normal estrus cycles were recruited in a prospective, parallel-group, placebo-controlled, double-blind, stratified-randomized animal trial with the equal allocation ratio of 1:1 challenging the efficacy of levamisole. Endometriosis was induced. After 6 weeks, laparotomy was performed to randomly excise one implant for histopathology assessment. Based on the results, they were stratified randomized and allocated (by software) to two groups of nine: levamisole (5 mg/rat/day) or placebo. After 6 weeks, necropsy was done. Two days before each laparotomy, blood samples and during the procedure, peritoneal wash were collected for ELISA.

Results: Seven rats showed success in treatment in the levamisole group, while three did in the other group. The histopathology results descriptively revealed a drop in the levamisole group, which was not meaningful statistically (0.66 ± 1.32 vs. 2.00 ± 1.50, p = 0.065). The comparisons of the post-treatment leukocytes and lymphocytes in the groups showed significant differences (11088.88 ± 5869.50 vs. 4677.77 ± 3476.98, p = 0.008, and 8588.88 ± 5721.32 vs. 3511.11 ± 2835.24, p = 0.014, respectively). The results of the cytokines were mostly, but not completely, in favor of the efficacy of levamisole.

Conclusion: This study indicates a possible successful role for levamisole in the treatment of experimental endometriosis. Further studies to assess the effects of high dose levamisole on endometriosis are recommended.