Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

The effect of exercise training with Nano selenium supplementation on LDHA, LDHB genes and LDHA/LDHB ratio at breast tumor tissue of mouse model

Articles in Press

Document Type : Original Article

Authors

Mohadeseh Akaberi 1
Mandana Gholami 2
Hossein Shirvani 3
Farshad Ghazalian 1
Hossein Abednatanzi 1

1 Department of Physical Education and Sport Sciences, SR.C., Islamic Azad university, Tehran, Iran.

2 Associate Professor, Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

3 Exercise Physiology Research Center, life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

10.22122/jeoct.2026.579301.1200
Abstract
This study investigated the effects of high intensity interval training (HIIT), nano-selenium supplementation, and their combination on the expression of LDHA, LDHB, and the LDHA/LDHB ratio in mice breast tumor tissue. Female mice (n = 32) were inoculated with mammary adenocarcinoma cells and randomly assigned to four groups (n = 8 each): tumor control (Tu), tumor + HIIT (Tu + Ex), tumor + nano-selenium (Tu + Nsel, 0.5 mg/kg/day orally), and tumor + HIIT + nano-selenium (Tu + Ex + Nsel). HIIT was performed on a treadmill (30 min/day, 5 days/week) for four weeks. One way ANOVA revealed significant differences among groups for LDHA expression (F = 38.66, p < 0.0001). Compared to the Tu group, all intervention groups (Tu + Ex, Tu + Nsel, and Tu + Ex + Nsel) showed a significant increase in LDHA expression (p < 0.05). The greatest increase was observed in the combined treatment group (Tu + Ex + Nsel), which was significantly higher than both Tu + Ex and Tu + Nsel (p < 0.001). For the LDHA/LDHB ratio, a significant overall effect was found (F = 163.87, p < 0.0001). The Tu + Nsel group exhibited a significant increase in the ratio compared to the Tu group (p < 0.05), whereas both Tu + Ex and Tu + Ex + Nsel showed a significant decrease in the ratio (p < 0.05). The ratio in the Tu + Nsel group was also significantly higher than in the two exercise containing groups (p < 0.05). HIIT and nano-selenium independently upregulate LDHA expression in breast tumor tissue, with an additive effect when combined. However, only nano-selenium alone increased the LDHA/LDHB ratio, while exercise based interventions (with or without nano-selenium) decreased this ratio. These findings suggest that exercise and nano-selenium differentially shift the balance between LDHA and LDHB, potentially influencing tumor lactate metabolism and the tumor microenvironment.

What is already known on this subject?

It is already known that LDHA and LDHB play key roles in tumor lactate metabolism, and a high LDHA/LDHB ratio is associated with increased cancer aggressiveness and poor prognosis. Exercise and selenium supplements have each been shown to modulate tumor metabolism individually, but the combined effect of high-intensity interval training (HIIT) and nano‑selenium on the LDHA/LDHB ratio in breast tumor tissue remained unknown.

 

What this study adds?

This study shows for the first time that both HIIT and nano‑selenium upregulate LDHA mRNA expression in breast tumor tissue, but they exert opposite effects on the LDHA/LDHB ratio: nano‑selenium alone increases the ratio, whereas exercise ‑based interventions (with or without nano‑selenium) decrease it. These findings suggest that exercise can shift the lactate dehydrogenase balance toward lactate oxidation and may serve as an adjunctive strategy to modulate breast tumor metabolism.

Keywords

Breast cancer
LDHA
LDHB
Nano-selenium
Exercise
Subjects

Acknowledgements

None.

Funding

None.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest The authors declare that there is no conflict of interest in the present research.

Ethical approval  All experimental procedures were approved by the Institutional Animal Ethics Committee and conformed to the ARRIVE guidelines and the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals (8th edition, 2011). Informed consent Animal study. 

Author contributions 

Conceptualization: M.A., Methodology: H.Sh., Software: M.Gh., Validation: H.A.,; Formal analysis: F.Gh.,; Investigation: H.Sh.,; Resources: M.A.,; Data curation: H.A.,; Writing - original draft: F.Gh.,; Writing–review & editing H.Sh.,; Visualization: M.A.,; Supervision: M.Gh.; Project administration: H.Sh.,.; Funding acquisition: M.A.        

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Journal of Exercise & Organ Cross Talk

Articles in Press, Accepted Manuscript
Available Online from 01 June 2026

  • Receive Date 22 March 2026
  • Revise Date 10 May 2026
  • Accept Date 12 May 2026

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