Key result
Reduced glutathione improves survival and limits cardiotoxicity from doxorubicin in preclinical models.
Why the study?
Doxorubicin use is clinically limited by cardiotoxicity driven by oxidative stress and inflammation, prompting investigation into the cardioprotective potential of reduced glutathione.
Does reduced glutathione prevent doxorubicin-induced cardiotoxicity and oxidative stress in a mouse model?
Does reduced glutathione prevent doxorubicin-induced cardiotoxicity and oxidative stress in a mouse model?
Reduced glutathione shows promise as an adjunct therapy to attenuate doxorubicin-induced cardiomyopathy by targeting the oxidative stress and inflammation axis.
Answers are grounded in this paper and cite their sources.
GSH attenuates doxorubicin cardiotoxicity in mice; hypothesis-generating and requires human trials before any clinical consideration.
Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat many types of cancer. Its use is limited because of the reported accompanied cardiotoxicity, which is driven by oxidative stress and inflammation. Herin, we explored the cardioprotective impact of reduced glutathione (GSH) against DOX-induced cardiac damage in a mice model and highlighted the dynamic interplay between pro-inflammatory and antioxidant mechanisms, with tissue damage markers and oxidative byproducts. Mice were divided into four groups and administered DOX, GSH, or a combination, and the outcomes were compared to untreated controls. DOX administration caused significant mortality, weight loss, elevated serum markers of cardiac injury (CK-MB and LDH), oxidative stress (MDA and iron), pro-inflammatory cytokines (IL-6, IL-17, and IL-23), and upregulated pro-inflammatory gene expression of STAT-3 and NFκB as well as downregulated gene expression of NRF-2 and HO-1. Histological analysis showed myocardial fibrosis, vacuolization, and apoptosis, as confirmed by a TUNEL assay. Meanwhile, treatment with GSH improved survival rate, attenuated weight loss, and restored cardiac function markers. Furthermore, GSH suppressed oxidative stress and inflammation, modulated gene expression, and declined histopathological damage. These findings demonstrated the multifaceted cardioprotection of GSH through the restoration of redox homeostasis and modulation of the pro- and anti-inflammatory responses. GSH supplementation emerges as a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, offering a strategy to improve cardiac health in cancer patients undergoing doxorubicin chemotherapy.
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Negm et al. (2025) studied Doxorubicin-induced cardiotoxicity (n=28). Reduced glutathione (GSH) vs. Doxorubicin alone and saline control was evaluated on Survival rate and cardiac injury markers (CK-MB, LDH, and histopathology) (p=<0.05). Reduced glutathione significantly improved survival and reduced doxorubicin-induced cardiotoxicity, oxidative stress, and myocardial fibrosis in a mouse model.
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