[ E6 Improves Vinorelbine-induced Immunosuppression in Zebrafish Through Its Metabolites Acetic Acid and Propionic Acid]

Overview

Journal Nan Fang Yi Ke Da Xue Xue Bao

Specialty General Medicine

Date 2025 Mar 3

PMID 40031977

Authors

X U Xinzhu

Lina Guo

Kangdi Zheng

Yan Ma

Shuxian Lin

Yingxi He

Wen Sheng

Suhua Xu

Feng Qiu

Affiliations

Soon will be listed here.

Abstract

Objectives: To explore the mechanism of E6 for improving vinorelbine-induced immunosuppression in zebrafish.

Methods: The intestinal colonization of E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in E6 fermentation supernatant and the metabolites of E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression.

Results: After inoculation, green fluorescence of FITC-labeled E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells.

Conclusions: E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.

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