Photoinactivation of leishmania amazonensis by Soranjidiol and white LED: Unraveling photodynamic and cell death mechanisms

Abstract

Cutaneous Leishmaniasis (CL) is part of the group of neglected diseases that pose significant global health challenges. Despite the many years since the discovery of pentavalent antimonials, the development of effective and affordable therapies remains a major obstacle. Antimicrobial photodynamic therapy (aPDT) is a localized treatment that has demonstrated efficacy in eliminating diverse pathogens without inducing resistance. Soranjidiol (Sor), a natural anthraquinone photosensitizer (PS), has shown promising in vitro and in vivo results against Leishmania amazonensis. This study aims to elucidate the photodynamic and cell death mechanisms of Sor by evaluating two different concentrations in the promastigote form and assessing its photoinactivation effects on the amastigote form of L. amazonensis. Our results demonstrate that Sor is a versatile and effective PS capable of eliminating promastigotes at low concentrations through the generation of reactive oxygen species and reactive nitrogen intermediates. Although aPDT is believed to generate both singlet oxygen and radicals, our findings indicate that type II reactions (1O₂) may be favoured at low Sor concentrations (singlet oxygen generation), leading to apoptosis; whereas type I reactions (superoxide anion) predominate at the highest concentration, resulting in necrosis.The amastigote form was also successfully photo-inactivated, resulting in a reduction in the infection index comparable to that of Amphotericin B, a second-line drug for CL treatment. Although complete amastigote elimination was not achieved, the application of serial aPDT sessions could potentially improve therapeutic efficacy under optimized conditions and might represent a promising strategy to promote lesion healing.