Therapeutic effect of topical tamoxifen in murine cutaneous leishmaniasis caused by Leishmania major

Antimicrob Agents Chemother. 2024 Dec 5;68(12):e0035824. doi: 10.1128/aac.00358-24. Epub 2024 Oct 24.

Abstract

Iran is one of the endemic regions of cutaneous leishmaniasis (CL) caused by Leishmania major. 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 Leishmania. The present study was conducted to investigate this theory in experimental CL caused by L. major. Forty female BALB/c mice aged 4 to 6 weeks were infected by injecting 1 × 106 L. major metacyclics (MRHO/IR/75/ER) in the base of the tail. After the appearance of Leishmania 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 (P = 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.

Keywords: Leishmania major; cutaneous leishmaniasis; tamoxifen.

MeSH terms

  • Administration, Topical*
  • Animals
  • Antiprotozoal Agents / pharmacology
  • Antiprotozoal Agents / therapeutic use
  • Female
  • Leishmania major* / drug effects
  • Leishmaniasis, Cutaneous* / drug therapy
  • Leishmaniasis, Cutaneous* / parasitology
  • Mice
  • Mice, Inbred BALB C*
  • Tamoxifen* / pharmacology
  • Tamoxifen* / therapeutic use

Substances

  • Tamoxifen
  • Antiprotozoal Agents