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

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Levamisole treatment in a rat endometriosis model reduced leukocytes and lymphocytes and showed a trend toward improved histopathology and cytokine profiles.

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This randomized, placebo-controlled, double-blind rat trial studied whether levamisole affects experimentally induced endometriosis, assessing implant histopathology plus peritoneal cytokines (interleukin-6, vascular endothelial growth factor-A, tumor necrosis factor-alpha) and blood leukocyte and lymphocyte counts at healthy, endometriotic, and post-treatment time points. Twenty-two Sprague–Dawley rats with normal estrus cycles were allocated to levamisole (5 mg/rat/day) or placebo after induction of endometriosis, with necropsy after 6 weeks and ELISA measurements from blood samples and peritoneal wash. Implant histopathology showed a descriptive reduction with levamisole but did not reach statistical significance (p=0.065), while post-treatment leukocyte and lymphocyte comparisons differed significantly between groups (both with lower counts in the levamisole group), and cytokine results were mostly—but not fully—in favor of levamisole. The paper explicitly notes a need for further studies, including assessing higher levamisole doses. This paper is centrally about endometriosis — it tests levamisole efficacy in a randomized rat model of experimental endometriosis.

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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. Similar content being viewed by others

References

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Adjuvants, Immunologic Endometriosis Levamisole Adjuvants, Immunologic Animals Double-Blind Method Endometriosis Endometriosis Female Humans Immunomodulation Interleukin-6 Interleukin-6 Leukocytes Levamisole Peritoneum Peritoneum Prospective Studies Rats Rats, Sprague-Dawley

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