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Table · dataset · 2026

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Listed in figshare and Loughborough Research Repository — shown once because both records carry DOI 10.6084/m9.figshare.33222513.v2

<p dir="ltr"><b>Aims:</b> Sepsis-induced myocardial injury (SIMI) is a leading cause of sepsis-related mortality with limited targeted therapies.

Description

Spermidine (SPD), a natural polyamine, is reported to mitigate multiple sepsis-associated syndromes, yet its functional role and molecular mechanism in SIMI remain poorly defined.<br><b>Materials and methods: </b>We evaluated the cardioprotective effects of SPD in a cecal ligation and puncture (CLP)‑induced septic rat model and lipopolysaccharide (LPS)‑stimulated H9C2 cardiomyocytes.

The Brain and muscle ARNT-like protein 1 (BMAL1)-mediated regulation on mitophagy was explored through molecular and functional assays, with mechanistic validation performed via BMAL1 knockdown and pharmacological inhibition using SR9009.</p><p dir="ltr"><b>Key findings: </b>SPD administration dose‑dependently improved survival in CLP rats, preserved cardiac contractile function, and reduced circulating levels of inflammatory cytokines and cardiac injury biomarkers.

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Contrary to the conventional view that SPD generally promotes cardiomyocyte autophagy under physiological conditions, our data indicate that SPD appears to suppress the abnormal activation of mitophagy in LPS-stimulated cardiomyocytes, as evidenced by its effects on the restoration of mitophagy-related protein expression levels, the maintenance of mitochondrial membrane potential (ΔΨm), and a reduction in reactive oxygen species (ROS) levels.

Mechanistically, SPD treatment upregulated BMAL1 and its downstream target Mitofusin-2 (MFN2), an upstream effector governing the initiation of mitophagy. These effects were largely attenuated by BMAL1 knockdown or SR9009 treatment, indicating that SPD‑mediated modulation of mitophagy might be mediated by BMAL1.<b>Significance: </b>Our findings provide experimental evidence supporting a cardioprotective role of SPD in SIMI and suggest that its beneficial effects involve the regulation of mitophagy in sepsis.

SPD shows potential as an adjunctive nutritional complementary therapy for SIMI.</p>

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Inferred from text
Heart 65%
Provenance · 2 source records, 29 field assertions
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figshareoai:figshare.com:article/3322251312 d agoJSON v1
Loughborough Research Repositoryoai:figshare.com:article/3322251312 d agoJSON v1
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