# Protective Role of Menthol Against Doxorubicin-Induced Cardiac Injury Through Suppression of TLR4/MAPK/NF-κB Signaling and Oxidative Stress

## TL;DR

This study shows that menthol can protect the heart from doxorubicin-induced damage by reducing inflammation and oxidative stress in rats.

## Contribution

The novel finding is that menthol suppresses TLR4/MAPK/NF-κB signaling and oxidative stress to mitigate doxorubicin cardiotoxicity.

## Key findings

- Menthol significantly reduced oxidative stress and inflammatory markers in doxorubicin-treated rats.
- Menthol treatment attenuated apoptosis and histopathological damage in cardiac tissues.
- Menthol did not interfere with doxorubicin's anticancer efficacy.

## Abstract

Background/Objectives: Doxorubicin (DOX) is a highly effective chemotherapeutic agent whose clinical use is limited by dose-dependent cardiotoxicity. This study aimed to investigate the potential protective effects of menthol against doxorubicin-induced cardiotoxicity (DIC) in a rat model. Methods: Forty rats were arbitrarily allocated into four groups: (1) normal control, (2) DOX-treated, (3) DOX + menthol treatment, and (4) menthol-only treatment. DOX (15 mg/kg) was applied intraperitoneally, and menthol (100 mg/kg) was applied orally for 7 days following the DOX injection. Cardiac tissue specimens and sera were collected for biochemical assays, histopathological analysis, and immunohistochemistry. Biomarkers of oxidative stress (MDA, GSH), inflammatory pathways (TLR4, MAPK, NF-κB, SREBP-1C), and apoptotic markers (P53, caspase-3) were assessed. Results: DOX employment caused remarkable rise in serum troponin levels (6.53 ± 0.98, p < 0.05), oxidative stress markers, and inflammatory proteins, alongside histopathological damage in cardiac tissues. Menthol treatment significantly suppressed oxidative stress (MDA, GSH), inflammation (TLR4, MAPK, NF-κB, SREBP-1C levels), and attenuated apoptosis (P53 and caspase-3 expression) (p < 0.05). Conclusions: Menthol may serve as a promising adjunctive therapy to reduce DOX cardiotoxicity without compromising DOX’s anticancer efficacy.