Objectives: Melittin, the main component of bee venom, is a natural anti-inflammatory substance, in addition to its ability to fight cancer, antiviral, and useful in diabetes treatment. This study seeks to determine whether melittin can protect renal tissue from sepsis-induced damage by preventing ferroptosis and explore the protective mechanism.
Methods: In this study, we investigated the specific protective mechanism of melittin against sepsis-induced renal injury by screening renal injury indicators and ferroptosis -related molecules and markers in animal and cellular models of sepsis.
Results: Our results showed that treatment with melittin attenuated the pathological changes in mice with lipopolysaccharide-induced acute kidney injury. Additionally, we found that melittin attenuated ferroptosis in kidney tissue by enhancing GPX4 expression, which ultimately led to the reduction of kidney tissue injury. Furthermore, we observed that melittin enhanced NRF2 nuclear translocation, which consequently upregulated GPX4 expression. our findings suggest that melittin may be a potential therapeutic agent for the treatment of sepsis-associated acute kidney injury by inhibiting ferroptosis through the GPX4/NRF2 pathway.
Conclusions: Our study reveals the protective mechanism of melittin in septic kidney injury and provides a new therapeutic direction for Sepsis-AKI.
Keywords: GPX4; Melittin; acute kidney injury; ferroptosis; lipopolysaccharide.