Blood Coral Polysaccharide Helps Prevent D-Gal/LPS-Induced Acute Liver Failure in Mice

Abstract

Objective: The liver protection of blood coral polysaccharide (BCP) was investigated.

Materials and methods: We evaluated the effect of BCP on liver pathology, liver function, oxidation and inflammation-related indicators of D-Gal/LPS-induced acute liver failure (ALF) mice in vivo.

Results: Liver index and liver pathology observation in mice showed that BCP could inhibit liver tissue swelling and hemorrhage, hepatocyte damage, and inflammatory infiltration in ALF. Serum liver function results showed that BCP effectively inhibits the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total bilirubin (TBil), alkaline phosphatase (AKP), myeloperoxidase (MPO). High dose-blood coral polysaccharide (H-BCP) was better than silymarin. Serum antioxidant and immune results showed that BCP increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px), and inhibited the levels of malondialdehyde (MDA) and nitric oxide (NO). Also, BCP increased immunoglobulins G (IgG) and A (IgA) levels, thereby enhancing humoral immunity. Liver anti-inflammatory ELISA results showed that BCP reduced the levels of interleukin (IL)-6, IL-1β, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, and enhanced the level of anti-inflammatory factor IL-10. H-BCP was the most effective treatment. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) of liver tissues confirmed that BCP increases the relative expression levels of antioxidant and anti-inflammatory-related cuprozinc superoxide dismutase (Cu/Zn-SOD, SOD1), manganese superoxide dismutase (Mn-SOD, SOD2), CAT, GSH, GSH-Px, and IL-10. In contrast, it inhibits inflammation-related genes IL-6, IL-1β, IL-17, TNF-α, IFN-γ, inducible nitric oxide synthase (iNOS, NOS2), and cyclooxygenase (COX)-2. In addition, BCP also inhibits the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and enhance B-cell inhibitor-α (IκB-α) gene relative expression in the liver, which may be related to NF-κB pathway inhibition.

Conclusion: BCP prevents D-Gal/LPS-induced ALF in mice, and its effect is concentration dependent.

Keywords: acute liver failure; anti-inflammatory; antioxidant; blood coral polysaccharide; immunomodulatory.

Figure 1

D-Gal/LPS-induced acute liver failure (ALF) model in mice.

Figure 2

Liver tissue appearance (A) and hematoxylin–eosin stain and liver injury score (B). ^a–d Mean values with different letters in the same bar graph are significantly different (P < 0.05), per Tukey’s test. The black arrows in the figure indicates the degree of liver cell looseness and swelling, and the black box indicates liver inflammatory factors. Normal: 0.9% normal saline gavage; Model: intraperitoneal injection of D-Gal/LPS; Silymarin: 100 mg/kg·bw gavage of silymarin, and intraperitoneal injection of D-Gal/LPS; L-BCP: 150 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS; H-BCP: 300 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS.

Figure 3

Gene expression of SOD1, SOD2, GSH, GSH-Px, and CAT in the liver. ^a–dMean values with different letters in the same bar graph are significantly different (P < 0.05), per Tukey’s test. Normal: 0.9% normal saline gavage; Model: intraperitoneal injection of D-Gal/LPS; Silymarin: 100 mg/kg·bw gavage of silymarin, and intraperitoneal injection of D-Gal/LPS; L-BCP: 150 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS; H-BCP: 300 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS.

Figure 4

Gene expression of IL-6, −10, −1β, −17, TNF-α, and IFN-γ in the liver. ^a–dMean values with different letters in the same bar graph are significantly different (P < 0.05), per Tukey’s test. Normal: 0.9% normal saline gavage; Model: intraperitoneal injection of D-Gal/LPS; Silymarin: 100 mg/kg·bw gavage of silymarin, and intraperitoneal injection of D-Gal/LPS; L-BCP: 150 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS; H-BCP: 300 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS.

Figure 5

Gene expression of IΚB-α, NF-kB, NOS2, and COX2 in the liver. ^a–d Mean values with different letters in the same bar graph are significantly different (P < 0.05), per Tukey’s test. Normal: 0.9% normal saline gavage; Model: intraperitoneal injection of D-Gal/LPS; Silymarin: 100 mg/kg·bw gavage of silymarin, and intraperitoneal injection of D-Gal/LPS; L-BCP: 150 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS; H-BCP: 300 mg/kg·bw gavage of blood coral polysaccharides, and intraperitoneal injection of D-Gal/LPS.