Ferulic acid alleviates lipopolysaccharide-induced acute liver injury in Megalobrama amblycephala

Abstract

Ferulic acid (FA) is a common phenolic compound that possesses antioxidant, anti-bacterial, anti-inflammatory, anti-hyperlipidemic, and immune-enhancing properties. Here, we established an oxidative stress and inflammatory model in blunt snout bream by intraperitoneally injecting lipopolysaccharide (LPS, 30 mg/kg BW (body weight)) to explore the effects of FA on oxidative stress, as well as its underlying protective mechanisms. Fish (96.43 ± 0.62 g) were randomly distributed into four groups: (1) saline injection after saline gavage, (2) LPS injection (30 mg/kg BW) after saline gavage, (3) LPS injection (30 mg/kg BW) after FA gavage (50 mg/kg BW), (4) LPS injection (30 mg/kg BW) after FA gavage (100 mg/kg BW). LPS injection induced liver damage at 24 hpi (hour post injection), with evidently increased hepatocyte apoptosis rates, as determined by TUNEL staining, and increased lysosomes, vacuoles, and visibly dilated hepatic sinusoids, as determined by hematoxylin-eosin (HE) staining. Moreover, plasma AST activity and HDL content significantly increased, and the TP, TC, TG, GLU, and C4 contents significantly decreased in the LPS-treated group. However, FA treatment showed lower apoptosis rates and fewer changes in liver structure than the LPS-treated group, which confirmed the replenishing effects of FA on LPS-induced liver damage. Moreover, plasma parameters including GLU, TP, AST, and C4, were effectively improved after 50 and/or 100 mg/kg BW FA administration. Furthermore, FA gavage (50 mg/kg BW) significantly decreased ROS content in blood. Our results also demonstrated that FA gavage enhanced hepatic antioxidant enzyme activities and increased GSH contents at 24 hpi to resist LPS-induced liver damage. Particularly, FA gavage (50 mg/kg BW and 100 mg/kg BW) significantly increased the levels of GSH and GST, whereas FA gavage at 50 mg/kg BW significantly increased SOD and GR activities. Additionally, FA gavage at 100 mg/kg BW increased GPx activity. Furthermore, the 50 mg/kg BW FA treatment also significantly increased the expression of sod, cat, and gpx mRNA. FA gavage (50 mg/kg BW and 100 mg/kg BW) also significantly decreased the contents of pro-inflammatory cytokines such as TNF-α and IL-1β under LPS stimulation at 96 hpi. Overall, the present study clarified the effect of sustained FA administration on LPS-induced oxidative stress, as well as its underlying protective mechanisms, thereby establishing a theoretical basis to further characterize the effects of FA as an antioxidant fish feed additive.