Key result
Sodium nitrate co-supplementation did not alleviate or exacerbate low-dose metronomic doxorubicin-induced cachexia in healthy mice, but it did protect against cardiac fibrosis.
Why the study?
The study was conducted to determine whether sodium nitrate progressed or alleviated doxorubicin-induced cachexia and muscle wasting, and whether a clinically relevant low-dose metronomic regimen was sufficient to induce cachexia in mice.
Does sodium nitrate co-supplementation prevent doxorubicin-induced cachexia and muscle wasting in a mouse model?
Does sodium nitrate co-supplementation prevent doxorubicin-induced cachexia and muscle wasting in a mouse model?
Answers are grounded in this paper and cite their sources.
Sodium nitrate co-supplementation protects against doxorubicin-induced cardiac fibrosis but does not alleviate doxorubicin-induced cachexia or skeletal muscle wasting in a low-dose metronomic mouse model.
The purpose of this study was to determine whether (1) sodium nitrate (SN) treatment progressed or alleviated doxorubicin (DOX)-induced cachexia and muscle wasting; and (2) if a more-clinically relevant low-dose metronomic (LDM) DOX treatment regimen compared to the high dosage bolus commonly used in animal research, was sufficient to induce cachexia in mice. Six-week old male Balb/C mice (n = 16) were treated with three intraperitoneal injections of either vehicle (0.9% NaCl; VEH) or DOX (4 mg/kg) over one week. To test the hypothesis that sodium nitrate treatment could protect against DOX-induced symptomology, a group of mice (n = 8) were treated with 1 mM NaNO3 in drinking water during DOX (4 mg/kg) treatment (DOX + SN). Body composition indices were assessed using echoMRI scanning, whilst physical and metabolic activity were assessed via indirect calorimetry, before and after the treatment regimen. Skeletal and cardiac muscles were excised to investigate histological and molecular parameters. LDM DOX treatment induced cachexia with significant impacts on both body and lean mass, and fatigue/malaise (i.e. it reduced voluntary wheel running and energy expenditure) that was associated with oxidative/nitrostative stress sufficient to induce the molecular cytotoxic stress regulator, nuclear factor erythroid-2-related factor 2 (NRF-2). SN co-treatment afforded no therapeutic potential, nor did it promote the wasting of lean tissue. Our data re-affirm a cardioprotective effect for SN against DOX-induced collagen deposition. In our mouse model, SN protected against LDM DOX-induced cardiac fibrosis but had no effect on cachexia at the conclusion of the regimen.
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Campelj et al. (2020) studied Doxorubicin-induced cachexia and cardiotoxicity (n=24). Sodium nitrate co-supplementation vs. Doxorubicin alone and Vehicle was evaluated on Cachexia (body mass displacement). Sodium nitrate co-supplementation did not alleviate or exacerbate low-dose metronomic doxorubicin-induced cachexia in healthy mice, but it did protect against cardiac fibrosis.
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