Efficacy of riboflavin/UVA treatment in modulating Candida tropicalis growth and cytokine profiles in the systemic candidiasis murine model

Abstract

Candidiasis, particularly from non-albicans Candida (NAC) species appealed as a global burden with high mortality in immunocompromised individuals. The biofilm formation aptitude of the Candida species has escalated the development of drug resistance in clinical settings, rendering it more difficult to treat candidiasis. Previous studies have shown that riboflavin in combination with UVA light poses candidacidal activity; however, its biological basis remains elusive. Thus, this study sought to investigate the antifungal activity and host immune response of UVA-photoactivated riboflavin against a systemic C. tropicalis infection in a mouse model. Downstream analyses at two time points, day 3 and 7, demonstrated that riboflavin and riboflavin/UVA treatments resulted in partial organ-specific reduction in fungal burden across organs and influenced haematological parameters. The interventions also has modulated host immune response, as evidenced by a downregulation of both pro-inflammatory and anti-inflammatory cytokines by day 7. The histopathological assessment revealed persistent inflammatory aggregates and invasion of yeast and pseudohyphae in the kidney tissue. The present data unveils that riboflavin and UVA-photoactivated riboflavin demonstrated partial antifungal efficacy and the ability to modulate the host immune response locally and systemically. Although these interventions reduced fungal burden in several organs, complete clearance was not achieved in the kidneys, where persistent fungal invasion and inflammation remained. These findings suggest that riboflavin-based photodynamic therapy holds potential as a supplemental therapeutic strategy, though further optimization is required to address deep-seated renal pathogenesis.