Hydrogen Gas Protects Heart from Cancer Drug Side Effects

Authors
Journal
International Immunopharmacology
Year
DOI
10.1016/j.intimp.2023.110071
Study Type
Rat
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Doxorubicin-induced Cardiotoxicity
Body System
Cardiovascular

TL;DR

Breathing in hydrogen gas can help protect the heart from damage caused by the cancer drug doxorubicin by improving the heart's self-cleaning process.

Key Finding

Hydrogen inhalation improved cardiac function and reduced heart cell damage in rats treated with doxorubicin by activating autophagy (a cellular cleanup process) through the AMPK/mTOR signaling pathway.

Summary

Researchers tested whether inhaling hydrogen gas could protect rat hearts from damage caused by doxorubicin, a chemotherapy drug known to harm the heart. They found that hydrogen inhalation improved heart function, reduced cell death, and activated a cellular cleanup process called autophagy through specific molecular pathways (AMPK and mTOR). This suggests hydrogen might help prevent heart damage in cancer patients receiving this chemotherapy.

Practical Takeaway

This is an early-stage rat study showing a potential mechanism by which hydrogen might protect against chemotherapy-induced heart damage. However, these results have not been tested in humans, and the study's sample size and duration were not reported. Much more research, including human trials, would be needed before hydrogen inhalation could be considered a treatment for this condition.

Abstract

Aims: Doxorubicin is a drug widely used in clinical cancer treatment, but severe cardiotoxicity limits its clinical application. Autophagy disorder is an important factor in the mechanism of doxorubicin-induced cardiac injury. As the smallest molecule in nature, hydrogen has various biological effects such as anti-oxidation, anti-apoptosis and regulation of autophagy. Hydrogen therapy is currently considered to be an emerging therapeutic method, but the effect and mechanism of hydrogen on doxorubicin-induced myocardial injury have not been determined. The purpose of this study was to investigate the protective effect of hydrogen inhalation on doxorubicin-induced chronic myocardial injury and its effect and mechanism on autophagy. Methods: In this study, we established a chronic heart injury model by intraperitoneal injection of doxorubicin in rats for 30 days, accumulating 20 mg/kg. The effect of hydrogen inhalation on the cardiac function in rats was explored by echocardiography, Elisa, and H&E staining. To clarify the influence of autophagy, we detected the expression of LC3 and related autophagy proteins in vivo and in vitro by immunofluorescence and western blot.In order to further explore the mechanism of autophagy, we added pathway inhibitors and used western blot to preliminarily investigate the protective effect of hydrogen inhalation on myocardial injury caused by doxorubicin. Results: Hydrogen inhalation can improve doxorubicin-induced cardiac function decline and pathological structural abnormalities in rats. It was confirmed by immunofluorescence that hydrogen treatment could restore the expression of autophagy marker protein LC3 (microtubule-associated protein 1 light chain 3) in cardiomyocytes reduced by doxorubicin, while reducing cardiomyocyte apoptosis. Mechanistically, Western blot results consistently showed that hydrogen treatment up-regulated the ratio of p-AMPK (phosphorylated AMP-dependent protein kinase) to AMPK and down-regulated p-mTOR (phosphorylated mammalian target of rapamycin) and mTOR ratio. Conclusions: These results suggest that hydrogen inhalation can activate autophagy through the AMPK/mTOR pathway and protect against myocardial injury induced by doxorubicin. Hydrogen inhalation therapy may be a potential treatment for doxorubicin-induced myocardial injury.