# Bisphenol F Drives Endoplasmic Reticulum Stress-Mediated Macrophage Polarization, Leading to Inflammation and Fibrosis in Mouse Kidneys

## TL;DR

This study shows how the chemical BPF harms mouse kidneys by causing stress in cells and changing immune cells, leading to inflammation and tissue damage.

## Contribution

The study reveals a novel mechanism linking BPF exposure to kidney damage via endoplasmic reticulum stress and macrophage polarization.

## Key findings

- BPF exposure causes kidney dysfunction and structural damage in mice.
- BPF activates endoplasmic reticulum stress and shifts macrophages toward pro-inflammatory and pro-fibrotic states.
- 4-phenylbutyric acid intervention reduces BPF-induced kidney damage in mice.

## Abstract

Bisphenol F (BPF) is a chemical compound that has found extensive application in the field of plastics manufacturing. BPF exposure leads to renal dysfunction; however, the mechanism is unclear. This study investigated BPF-induced nephrotoxicity using 50 male Kunming mice divided into five groups: control (C), low-dose (L, 0.5 mg/kg), medium-dose (M, 5 mg/kg), high-dose (H, 50 mg/kg) BPF, and an intervention group receiving 4-phenylbutyric acid (4-PBA) plus BPF. Treatments were administered daily by oral gavage for 28 days. Renal function was assessed via serum creatinine (SCr), while inflammation and fibrosis were evaluated using histology, immunohistochemistry, immunofluorescence, ELISA, qRT-PCR, and Western blotting. Preliminary results suggest that BPF causes structural damage and dysfunction in the mice kidney. Furthermore, BPF-induced renal inflammation and fibrosis, accompanied by the activation of endoplasmic reticulum (ER) stress and the polarization of renal macrophages toward M1 and M2 types. In vitro, BPF (40 µM, 48 h) induced similar effects in Raw264.7 cells, which were mitigated by 4-PBA pretreatment. Finally, 4-PBA intervention confirmed that BPF triggers macrophage polarization via ER stress, leading to inflammation and fibrosis, ultimately causing renal dysfunction in vivo. This study provides new insights into BPF nephrotoxicity and a basis for therapeutic strategies.