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

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.