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

Abstract 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 LPS-induced neonatal sepsis rat model and explored underlying pathways. Methods: Neonatal Wistar rats received LPS (5 mg/kg, i.p.) and were assigned to 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; MDA; SOD), NO metabolites (NO 2 − , NO 3 − , NO 2 − /NO 3 − ), inflammation (qPCR/Western blot for TNF-α, IL-1β, IFN-γ), apoptosis (Bax/Caspase3, TUNEL), MAPK and 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 protects against neonatal LPS-induced liver injury by preserving redox homeostasis, limiting inflammation and apoptosis, and suppressing ERK/JNK signaling, supporting SDX as a potential therapy for neonatal sepsis–associated hepatic injury.