# Dasatinib and quercetin mitigate radiation-induced lung injury by eliminating senescent cells in a rat model

## TL;DR

Dasatinib and quercetin reduce radiation-induced lung injury in rats by targeting and eliminating senescent cells.

## Contribution

This study demonstrates that dasatinib and quercetin mitigate radiation-induced lung injury by reducing senescent cell burden and suppressing inflammatory responses.

## Key findings

- DQ treatment reduced inflammatory cell infiltration and collagen deposition in irradiated lungs.
- DQ decreased senescence markers and SASP factors while activating apoptotic pathways.
- Transcriptomic analysis linked DQ effects to p53, MAPK, PI3K-Akt, and mitophagy signaling modulation.

## Abstract

Radiation-induced lung injury (RILI) is a major dose-limiting toxicity in thoracic radiotherapy, and accumulating evidence implicates radiation-induced cellular senescence in its pathogenesis. This study aimed to investigate whether combination therapy with dasatinib and quercetin (DQ) could mitigate RILI by reducing senescent cell burden.

A rat model of RILI was established using a single 30 Gy irradiation to the right lung. Pulmonary pathological changes, fibrosis, DNA damage, and cellular senescence were assessed by histology, immunofluorescence, senescence-associated β-galactosidase staining, Western blotting and immunohistochemistry. Transcriptomic profiling was performed to explore the underlying molecular mechanisms.

Compared with irradiation alone, DQ treatment significantly alleviated radiation-induced inflammatory cell infiltration and collagen deposition, reduced γH2AX levels, decreased senescence-associated markers p53, p21, and p16, and suppressed multiple senescence-associated secretory phenotype (SASP) factors. Transcriptomic analysis indicated that DQ-mediated effects were closely associated with activation of apoptotic pathways and modulation of p53, MAPK, PI3K-Akt and mitophagy signaling cascades.

DQ attenuated RILI in rats, with effects consistent with the reduced radiation-induced senescent cells and suppression of senescence-associated inflammatory responses.