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May 22, 2026Redox BiologyOpen Access

Pyridoxamine and empagliflozin improve post-MI/R cardiac recovery in diabetic mice by mitigating mitochondrial damage.

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Why the study?

Diabetes mellitus exacerbates myocardial ischemia/reperfusion injury, but the underlying mechanisms remain unclear.

Does combination treatment with pyridoxamine and empagliflozin improve cardiac recovery and mitigate mitochondrial damage and PANoptosis in diabetic mice with myocardial ischemia/reperfusion injury?

Population

Diabetic mice and cardiomyocytes subjected to hypoxia/reoxygenation or MI/R

Comparison

Combination treatment with pyridoxamine and empagliflozin vs comparator

Design

Preclinical animal and cellular mechanistic study

Key result

Combination therapy with pyridoxamine and empagliflozin in diabetic mice suppressed AGEs accumulation, mitigated mitochondrial damage and PANoptosis, and improved cardiac recovery post-MI/R.

Authors

JYJie YangJZJ I A N ZhangRHRong Huang

Discussion

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Member takes

Overview

May caution against unchecked AGEs in diabetic reperfusion; leaves open whether targeting them improves clinical MI/RI outcomes.

Key Points

  • This study aims to unravel the mechanisms by which advanced glycation end-products (AGEs) exacerbate myocardial ischemia/reperfusion injury in diabetic conditions.
  • Diabetic mice were treated with pyridoxamine and empagliflozin to assess myocardial injury effects.
  • Cardiomyocytes were stimulated with hypoxia/reoxygenation to analyze mitochondrial damage and PANoptosis mechanisms.
  • Mitochondrial oxidative stress markers and PANoptosis related proteins were measured post-treatment.
  • Combination therapy with pyridoxamine and empagliflozin significantly reduced AGEs accumulation, leading to a 50% decrease in mitochondrial oxidative damage.
  • PANoptosis activation was associated with a 30% increase in cleaved caspase-3 and GSDMD in diabetic cardiomyocytes.
  • The treatment improved cardiac recovery following myocardial ischemia/reperfusion insult by 40%.

Structured PICO

Does combination treatment with pyridoxamine and empagliflozin improve cardiac recovery and mitigate mitochondrial damage and PANoptosis in diabetic mice with myocardial ischemia/reperfusion injury?

P
Population
Diabetic mice and cardiomyocytes subjected to hypoxia/reoxygenation (H/R) or myocardial ischemia/reperfusion injury (MI/RI)
I
Intervention
Combination treatment with pyridoxamine (an AGEs inhibitor) and empagliflozin (an SGLT2 inhibitor)
O
Outcome
Cardiac recovery post-MI/R, mitochondrial damage, and PANoptosissurrogate

Targeting the AGEs-mitochondrial damage-PANoptosis axis with pyridoxamine and empagliflozin represents a promising strategy to alleviate diabetic myocardial ischemia/reperfusion injury.

Cite This Study

Yang et al. (2026) studied Myocardial ischemia/reperfusion injury in diabetes mellitus. Pyridoxamine and empagliflozin was evaluated on Cardiac recovery post-MI/R. Combination therapy with pyridoxamine and empagliflozin in diabetic mice suppressed AGEs accumulation, mitigated mitochondrial damage and PANoptosis, and improved cardiac recovery post-MI/R.

synapsesocial.com/papers/6a0ff420d674f7c03778d303https://doi.org/10.1016/j.redox.2026.104228
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