# Melatonin attenuates cardiac oxidative stress in diabetic rats following acute exhaustive exercise

**Authors:** Carol Nguyen, Rafael Ishihara Figueiroa, Cristiano Mendes da Silva, Elaine Hatanaka, Gary Sweeney, Rafael Herling Lambertucci

PMC · DOI: 10.1016/j.cstres.2025.100126 · 2025-10-17

## TL;DR

Melatonin helps reduce heart damage caused by oxidative stress in diabetic rats, especially when combined with exercise.

## Contribution

The study shows that melatonin supplementation improves antioxidant defenses in diabetic rats during and after exercise.

## Key findings

- Melatonin reduces oxidative stress index and lipid peroxidation in diabetic rats after exercise.
- Melatonin increases total glutathione levels and modulates antioxidant enzyme mRNA expression.
- Combining melatonin with exercise may offer synergistic protection against oxidative damage in diabetic hearts.

## Abstract

Diabetes mellitus affects millions of people worldwide and there is evidence linking the increase of oxidative stress to the development of diabetic cardiomyopathy. Melatonin has been found to possess powerful antioxidant properties via modulating both enzymatic and non-enzymatic antioxidant systems.

To evaluate the antioxidant potential of melatonin on the heart of diabetic animals at basal conditions and following 2 h of strenuous exercise.

Diabetic animals were divided into two groups: non-supplemented and supplemented (melatonin). We evaluated oxidative stress biomarkers, total glutathione amount, oxidative stress index and antioxidant enzymes mRNA expression, immediately after an exhaustive exercise (IA group), and 2 h after exhausted exercise (2 h group). We also included a non-exercised group (0 h).

Comparing to non-exercised animals, exercise immediately induced an increase of nitrite and total antioxidant status in non-supplemented and supplemented animals, respectively. In melatonin-supplemented animals, the oxidative stress index decreased immediately after exercise (IA group) compared to non-exercised animals (0 h), an effect not seen in the non-supplemented group. Compared to non-supplemented, melatonin supplementation was shown to attenuate TBARS at all time points and increase total glutathione content at times 0 h and IA. mRNA expression of some antioxidant enzymes (CAT and GPX) was modulated by melatonin, especially when associated with exercise [catalase (CAT) and Cu, Zn superoxide dismutase (SOD)].

Our findings demonstrate that melatonin confers antioxidant protection to the diabetic heart, primarily by increasing glutathione levels and attenuating lipid peroxidation. This establishes a protective state that enhances cardiac resilience, and the combination of melatonin and exercise may offer synergistic benefits against acute, stress-induced oxidative damage in diabetic animals.

## Linked entities

- **Proteins:** CAT (catalase), GPX (probable phospholipid hydroperoxide glutathione peroxidase), SOD1 (superoxide dismutase 1)
- **Chemicals:** melatonin (PubChem CID 896), nitrite (PubChem CID 946), glutathione (PubChem CID 124886)
- **Diseases:** diabetes mellitus (MONDO:0005015)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** CAT (catalase) [NCBI Gene 847]
- **Diseases:** Diabetes mellitus (MESH:D003920), diabetic cardiomyopathy (MESH:D058065)
- **Chemicals:** Melatonin (MESH:D008550), TBARS (MESH:D017392), nitrite (MESH:D009573), lipid (MESH:D008055), glutathione (MESH:D005978)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12616075/full.md

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Source: https://tomesphere.com/paper/PMC12616075