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

Abstract

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. 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. 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. 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.