# Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue

## TL;DR

This study shows that high doses of oxaliplatin chemotherapy cause heart damage in mice by disrupting heart energy metabolism.

## Contribution

The study reveals how chronic oxaliplatin treatment alters heart energy metabolism, leading to cardiotoxicity.

## Key findings

- Oxaliplatin causes focal myocardial necrosis and neutrophil infiltration in mice hearts.
- Chronic oxaliplatin treatment alters gene expression in fatty acid oxidation and glycolysis pathways.
- The findings suggest potential for early detection and treatment of oxaliplatin-induced heart damage.

## Abstract

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed with ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart’s energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation and glycolysis leading to the glycolysis switch. Our study can be used for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage and identifying therapeutic methods to minimize heart failure.

The online version contains supplementary material available at 10.1186/s40959-026-00453-7.