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Background <p>Neonatal sepsis frequently causes liver dysfunction driven by oxidative/nitrosative stress, inflammation, and hepatocyte death. This study evaluated the hepatoprotective effects of Sulodexide (SDX) in an lipopolysaccharides (LPS)-induced neonatal sepsis rat model and explored underlying pathways.</p> Methods <p>Neonatal Wistar rats received LPS (1&#xa0;mg/kg, i.p.) and were assigned to five groups: Control (CT), LPS, LPS + SDX (40 LSU/kg), SDX, or LPS+Dexamethasone (DEX, 0.5&#xa0;mg/kg). Liver injury was assessed by serum ALT/AST and H&amp;E staining. Hepatic edema (wet-to-dry ratio), antioxidant capacity (FRAP, ABTS, malondialdehyde, MDA; superoxide dismutase, SOD), NO metabolites (NO<sub>2</sub><sup>−</sup>, NO<sub>3</sub><sup>−</sup>, NO<sub>2</sub><sup>−</sup>/NO<sub>3</sub><sup>−</sup>), inflammation (qPCR/Western blot for TNF-α, IL-1β, IFN-γ), apoptosis (Bax, Caspase3, TUNEL), Mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling were evaluated. Transcriptomics with KEGG enrichment was performed.</p> Result <p>LPS markedly increased ALT/AST, worsened histopathology and edema, reduced FRAP/ABTS and SOD, disrupted NO metabolites, elevated inflammatory cytokines, and increased apoptosis. Under LPS conditions, SDX significantly lowered both AST and ALT, improved histology and W/D ratio, restored antioxidant capacity, suppressed inflammatory mediators, and reduced apoptosis; SDX alone did not raise ALT/AST versus CT. SDX also reduced ERK/JNK and NF-κB phosphorylation.</p> Conclusion <p>SDX prevents LPS-induced liver injury in newborns by maintaining redox homeostasis, suppressing inflammation and apoptosis, and inhibiting NF-κB/ERK/JNK signaling; this suggests that SDX is a potential therapeutic agent for treating liver injury associated with neonatal sepsis.</p>

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Sulodexide protects against sepsis-induced liver injury in neonatal rat by attenuating oxidative stress, apoptosis, and NF-κB/MAPK signaling

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Wei Lu,
  • Kang Fu,
  • Xinming Zhang,
  • Pedro Antonio Valdes-Sosa,
  • Jun Wang,
  • Fuzhong Xing

摘要

Background

Neonatal sepsis frequently causes liver dysfunction driven by oxidative/nitrosative stress, inflammation, and hepatocyte death. This study evaluated the hepatoprotective effects of Sulodexide (SDX) in an lipopolysaccharides (LPS)-induced neonatal sepsis rat model and explored underlying pathways.

Methods

Neonatal Wistar rats received LPS (1 mg/kg, i.p.) and were assigned to five groups: Control (CT), LPS, LPS + SDX (40 LSU/kg), SDX, or LPS+Dexamethasone (DEX, 0.5 mg/kg). Liver injury was assessed by serum ALT/AST and H&E staining. Hepatic edema (wet-to-dry ratio), antioxidant capacity (FRAP, ABTS, malondialdehyde, MDA; superoxide dismutase, SOD), NO metabolites (NO2−, NO3−, NO2−/NO3−), inflammation (qPCR/Western blot for TNF-α, IL-1β, IFN-γ), apoptosis (Bax, Caspase3, TUNEL), Mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling were evaluated. Transcriptomics with KEGG enrichment was performed.

Result

LPS markedly increased ALT/AST, worsened histopathology and edema, reduced FRAP/ABTS and SOD, disrupted NO metabolites, elevated inflammatory cytokines, and increased apoptosis. Under LPS conditions, SDX significantly lowered both AST and ALT, improved histology and W/D ratio, restored antioxidant capacity, suppressed inflammatory mediators, and reduced apoptosis; SDX alone did not raise ALT/AST versus CT. SDX also reduced ERK/JNK and NF-κB phosphorylation.

Conclusion

SDX prevents LPS-induced liver injury in newborns by maintaining redox homeostasis, suppressing inflammation and apoptosis, and inhibiting NF-κB/ERK/JNK signaling; this suggests that SDX is a potential therapeutic agent for treating liver injury associated with neonatal sepsis.