Melittin alleviates sepsis-induced acute kidney injury by promoting GPX4 expression to inhibit ferroptosis

ABSTRACT

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:

• Melittin
• ferroptosis
• GPX4
• acute kidney injury
• lipopolysaccharide

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used to support the findings of this study are avail-able from the corresponding author upon request.

Authors contributions

YF-Z completed animal experiments and some cellular experiments as well as writing the article. JZ-L performed urea nitrogen, blood creatinine assays and hematoxylin–eosin staining, in addition to as the remaining animal experiments. MX-Y completed the remaining cellular experiments. HX-L and HY-Z contributed to the experimental design and provided financial support, while CY-G was responsible for data collation and analysis. YY-D and ZM-W provided expertise in animal modeling technology and experimental conditions, and were responsible for the collection of experimental samples.

Additional information

Funding

This work was supported by Natural Science Research General Project of Shanxi Provincial Basic Research Program, from Science and Technology Department of Shanxi Province (No. 20210302123484).