Utility of the combination of hederagenin glucoside saponins and chromane hydrazone in the topical treatment of canine cutaneous leishmaniasis. An observational study

Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2–2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6–24 h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2–2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24 months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.