MOLECULAR HYDROGEN AS A MODULATOR OF OXIDATIVE STRESS AND INFLAMMATION IN DOXORUBICIN-INDUCED TOXICITY
DOI:
https://doi.org/10.11603/1811-2471.2025.v.i3.15557Keywords:
molecular hydrogen, doxorubicin, oxidative stress, TNF-α, IL-1β, antioxidant defense, subchronic toxicity, ratsAbstract
SUMMARY. Doxorubicin is an effective anthracycline widely used in chemotherapy, but its clinical use is limited by toxic side effects, especially cardiotoxicity associated with oxidative stress and inflammation. Molecular hydrogen (H2) exhibits antioxidant and anti-inflammatory properties by selectively neutralizing hydroxyl radicals and peroxynitrite.
The aim – to investigate the effect of molecular hydrogen-enriched water on oxidative stress and inflammation in doxorubicin-induced toxicity in rats.
Material and Methods. The experiment was conducted on adult male rats randomized into four groups: control, doxorubicin (DOX), doxorubicin + hydrogen-enriched water (DOX+H2-water), and hydrogen-enriched water (H2-water). Intraperitoneal injections of doxorubicin were administered at a dose of 5 mg/kg, with a cumulative dose of 20 mg/kg. Rats were sacrificed on the 29th day of the experiment. Levels of pro-inflammatory cytokines (TNF-α, IL-1β), oxidative stress markers (MDA, 8-isoprostane, carbonyl groups), antioxidant enzyme activities (catalase, superoxide dismutase), and reduced glutathione content were measured.
Results. Doxorubicin significantly increased the level of pro-inflammatory cytokines, enhanced oxidative stress and elevated lipid and protein peroxidation: increased levels of MDA, 8-isoprostane, and protein carbonyl groups were observed. At the same time, the suppression of activity of catalase, superoxide dismutase and reduced glutathione levels confirmed the inhibition of antioxidant defense. Consumption of hydrogen-enriched water reduced pro-inflammatory cytokines by 33–35%, decreased oxidative stress markers, and improved antioxidant defense. Consumption of hydrogen-enriched water did not cause deviations in indices compared to control group animals.
Conclusions. Molecular hydrogen-enriched water effectively attenuates doxorubicin-induced oxidative stress and inflammation by modulating the pro-oxidant-antioxidant balance and cytokines profile. This approach is promising as an adjunct therapy to reduce anthracycline antibiotic toxicity without compromising antitumor efficacy. Further research into the mechanisms of molecular hydrogen action in clinical settings is recommended.
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