Fluvoxamine Attenuates Liver Injury in Lipopolysaccharide-Induced Sepsis: Via Nrf2/HO-1 Pathway

The search for new treatments for sepsis is a pivotal subject of survey owing to the high mortality of sepsis. Sepsis can cause serious injury to many vital organs, including the liver. This study investigated the potential therapeutic impacts of fluvoxamine (FLV) against liver injury in a lipopolysaccharide (LPS)-induced sepsis model. Thirty-two female Wistar Albino rats were divided into four equal groups: control, LPS (5 mg/kg, i.p., single dose), LPS + FLV(5 mg/kg, i.p., single dose+50 mg/kg, i.p., single dose, 30 min before LPS application) and FLV(50 mg/kg, i.p., single dose). Six hours after LPS application, blood and liver tissues were gathered under anesthesia for biochemical, histopathological, and immunohistochemical analyses. The RT-qPCR analyzed the mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2), glycogen synthase kinase-3 (GSK3ß), kelch-like ECH-associated protein 1 (Keap1), and heme oxygenase-1 (HO-1). LPS administration caused significant histopathological changes in the liver and increased oxidative stress. It increased the number of TNF-α, osteopontin (OPN), and serum amyloid A (SAA) immune positive cells associated with inflammation and decreased Nrf2, GSK3ß, Keap1, and HO-1 gene expressions associated with antioxidant defense. Additionally, serum alanine aminotransferase (ALT) level significantly increased. In the LPS + FLV and FLV groups, improvement in histopathological findings and a significant decrease in oxidative stress were detected. TNF-α, OPN, and SAA expression decreased, and Nrf2, GSK3ß, Keap1, and HO-1 gene expressions increased. The decrease in serum aspartate aminotransferase (AST) and ALT was found to be significant only in the FLV group. Our findings therefore provide new evidence that FLV reduces LPS-induced liver injury.