Therapeutic effect of topical tamoxifen in murine cutaneous leishmaniasis caused by <i>Leishmania major</i>

Iran is one of the endemic regions of cutaneous leishmaniasis (CL) caused by <i>Leishmania major</i>. There is no protective vaccine available against CL available, and the most effective strategy is a definitive treatment. Topical medications can be an excellent option for this purpose. Tamoxifen, a cancer control drug, has properties such as inducing cell apoptosis and anti-parasitic activity, which can be useful in controlling eukaryotic parasites such as <i>Leishmania</i>. The present study was conducted to investigate this theory in experimental CL caused by <i>L. major</i>. Forty female BALB/c mice aged 4 to 6 weeks were infected by injecting 1 × 10⁶ <i>L. major</i> metacyclics (MRHO/IR/75/ER) in the base of the tail. After the appearance of <i>Leishmania</i> nodules, mice were divided into five test and control groups. Two drug formulations were used: tamoxifen 1% in ethanol and tamoxifen citrate ointment 0.1%. The effectiveness of each formula was evaluated by determining the mean size of the ulcers and parasite burden after a 28-day treatment period. Both formulations showed reduced ulcer mean sizes. However, only the tamoxifen citrate ointment group demonstrated a statistically significant reduction (<i>P</i> = 0.049). The parasite burden decreased by 40.83% for the ointment group and 33.67% for the ethanol solution. Other control groups showed lesser reductions. This study partially demonstrated the effectiveness of topical tamoxifen on CL lesions in a murine model. It can provide a basis for further research on the therapeutic effects of different topical tamoxifen formulations.