# Voluntarily wheel running protects doxorubicin-induced kidney injury by inhibiting oxidative stress through mitochondrial function

## TL;DR

Voluntary running in mice reduces kidney damage from doxorubicin by improving mitochondrial function and lowering oxidative stress.

## Contribution

This study shows voluntary exercise protects against doxorubicin-induced kidney injury through mitochondrial and oxidative stress mechanisms.

## Key findings

- Voluntary wheel running reduced serum creatinine, urea nitrogen, and uric acid levels in doxorubicin-treated mice.
- Exercise decreased oxidative stress markers and mitochondrial damage in kidney tissue.
- Exercise increased antiapoptotic proteins and reduced TUNEL-positive cells in renal tissue.

## Abstract

Doxorubicin (DOX) has a broad anticancer spectrum and precise anticancer effects, but its clinical application is limited by severe multiorgan toxicity, among which nephrotoxicity is one of the main adverse reactions. In this study, the protective effect of voluntary wheel running on nephrotoxicity induced by DOX was observed, and its mechanism was initially discussed.

Forty male C57BL/6 mice were randomly divided into a control group (CTR), a voluntary wheel running group (EX), a doxorubicin model group (DOX) and a doxorubicin combined with voluntary wheel running group (COM). After 2 weeks of exercise, the mice were sacrificed. Serum creatinine (CREA), urea nitrogen (BUN), uric acid (UA), carbon dioxide combining power (CO2-CP), renal tissue apoptosis, oxidative stress and mitochondrial function indicators were assessed.

Compared with those in the DOX group, the concentrations of CREA, BUN and UA decreased, the number of TUNEL-positive cells in kidney tissue decreased, the expression of antiapoptotic proteins increased, and the expression of proapoptotic proteins decreased in the COM group. In addition, the COM can reduce the ROS and MDA contents in kidney tissue, reduce peroxide accumulation and alleviate mitochondrial respiratory chain damage caused by DOX.

Voluntary wheel running can improve the mitochondrial function of renal cells and reduce oxidative stress damage, thus playing a protective role against nephrotoxicity caused by DOX. This study provides a new way to reduce the adverse reactions to chemotherapy in combination with the application of chemical drugs.