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Synergistic Cardioprotection of Colchicine and Hyperbaric Oxygen Therapy in a Rat Model of Remote
Şahhan Kılıç1, Süha Asal1, Mert Babaoğlu2
1Department of Cardiology, Ministry of Health Çorlu State Hospital, Çorlu, Tekirdağ, Türkiye.
Purpose:
Lower extremity ischemia-reperfusion injury (IRI) triggers systemic inflammation and oxidative stress, causing myocardial remote ischemia-reperfusion injury (MIRI). Current treatments are limited.
Methods:
Male Sprague-Dawley rats (n = 6 per group) were assigned to Sham, I/R, I/R + colchicine (C), I/R + HBOT, and I/R + HBOT + C. IRI was induced by 60-min infrarenal aortic clamping and 120-h reperfusion.
Treatment:
Once daily colchicine (0.3 mg/kg) and HBOT (2.5 ATA, 100% O2) twice daily were administered for 5 days post-reperfusion. Cardiac damage, oxidative stress, inflammation, and NRF-2/HO-1 signaling were measured, and electrocardiography (ECG) was performed.
Results:
I/R caused severe MIRI (Hs-Troponin T: 568.54 pg/mL; heart OSI: 20.98; TNF-α: 582.89 pg/mL). Both monotherapies reduced damage, but HBOT + C was superior: Hs-Troponin T 342.07 pg/mL, OSI 2.26, TNF-α 278.82 pg/mL, and IL-6 12.25 pg/mL, with the upper end of the interquartile range for NRF-2 (41.03) and HO-1 (14.45) activation and restored redox balance (%DIS/NT: 26.31). No differences were observed between groups on the ECG.
Conclusions:
Colchicine suppresses inflammation, relieving inhibition of antioxidant defenses, enabling HBOT to fully activate NRF-2/HO-1. This synergistic HBOT + C strategy effectively mitigates MIRI, offering a promising multimodal therapy for remote organ protection after major ischemia.
Insights
Lower extremity ischemia-reperfusion injury (IRI) causes heart damage. A combination of hyperbaric oxygen therapy (HBOT) and colchicine (C) significantly reduced myocardial injury and inflammation in rats, offering a novel treatment.
Area of Science:
- Cardiovascular Research
- Translational Medicine
- Biomedical Engineering
Background:
- Lower extremity ischemia-reperfusion injury (IRI) induces systemic inflammation and oxidative stress, leading to remote myocardial injury (MIRI).
- Current therapeutic strategies for MIRI are limited, necessitating the exploration of novel treatment approaches.
Purpose of the Study:
- To investigate the efficacy of hyperbaric oxygen therapy (HBOT) and colchicine (C), alone and in combination, in mitigating MIRI induced by lower extremity IRI.
- To elucidate the underlying mechanisms, including the modulation of oxidative stress, inflammation, and the NRF-2/HO-1 signaling pathway.
Main Methods:
- Male Sprague-Dawley rats underwent IRI induction via infrarenal aortic clamping.
- Treatment groups included Sham, I/R, I/R + colchicine, I/R + HBOT, and I/R + HBOT + colchicine.
- Cardiac damage markers, oxidative stress indices, inflammatory cytokines, and NRF-2/HO-1 pathway activation were assessed post-reperfusion.
Main Results:
- IRI induced significant MIRI, evidenced by elevated cardiac damage markers and inflammatory cytokines.
- Both HBOT and colchicine monotherapies demonstrated protective effects against MIRI.
- The combination of HBOT and colchicine exhibited superior efficacy, significantly reducing cardiac damage, oxidative stress, and inflammation, while promoting NRF-2/HO-1 pathway activation and restoring redox balance.
Conclusions:
- The synergistic combination of HBOT and colchicine effectively mitigates MIRI by suppressing inflammation and enhancing antioxidant defenses via the NRF-2/HO-1 pathway.
- This multimodal therapeutic strategy presents a promising approach for remote organ protection following major ischemic events.
- Further research is warranted to translate these findings into clinical practice for managing IRI-induced MIRI.
