Jinliang Du

Anti-inflammatory and hepatoprotective effects of Ganoderma lucidum polysaccharides on carbon tetrachloride-induced hepatocyte damage in common carp (Cyprinus carpio L.)

The aim of this study was to investigate the anti-inflammatory and hepatoprotective effects of Ganoderma lucidum polysaccharides (GLPS) on carbon tetrachloride (CCl4)-induced hepatocyte damage in common carp (Cyprinus carpio L.). GLPS (0.1, 0.3, 0.6mg/ml) were added to the primary hepatocytes before (pre-treatment), after (post-treatment) and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl4 at the concentration of 8mM in the culture medium. The supernatants and cells were collected respectively to detect the biochemical indicators. The levels of TNF-α, IL-1β, caspase-3 and caspase-8 were measured by ELISA, the mRNA expressions of CYP1A and CYP3A were determined by RT-PCR, and western blotting was used to assay the relative protein expressions of c-Rel and p65. Results showed that GLPS significantly improved cell viability and inhibited the elevations of the marker enzymes (GOT, GPT, LDH) and MDA induced by CCl4, and markedly increased the level of SOD. Treatments with GLPS resulted in a significant decrease in the expressions of CYP1A and CYP3A, and significantly down-regulated extrinsic apoptosis and immune inflammatory response. In brief, the present study showed that GLPS can protect hepatocyte injury induced by CCl4 through inhibiting lipid peroxidation, elevating antioxidant enzyme activity and suppressing apoptosis and immune inflammatory response.

Dexamethasone-induced hepatomegaly and steatosis in larval zebrafish

Fish hepatobiliary syndrome, characterized by hepatomegaly and fatty liver, has been frequently reported in many cultured fish species and has caused a dramatic economic loss in China. Glucocorticoids are thought to be important non-nutritional factors for hepatomegaly and fatty liver development. In the present study, a dexamethasone-induced zebrafish model of fatty liver and hepatomegaly was established, and the role of glucocorticoid receptor (GR) in the development of hepatomegaly and fatty liver was investigated using developing zebrafish. Exposure of larval zebrafish at 5 days post fertilization (dpf) to dexamethasone for 24 hr caused significant increases of liver size and number of fish with hepatic steatosis at 6 dpf. The increase of liver size caused by dexamethasone was significantly reversed by treatment with RU486, a GR antagonist, and by gene knock-down with a morpholino against the GR. The dexamethasone-induced hepatic steatosis was also inhibited by treatment with RU486. Overall, the results highlight larval zebrafish as a useful model for stress-induced liver failure.

Hepatoprotective and antioxidant effects of dietary Glycyrrhiza polysaccharide against TCDD-induced hepatic injury and RT-PCR quantification of AHR2, ARNT2, CYP1A mRNA in Jian Carp (Cyprinus carpio var. Jian)

To evaluate the protective effects of Glycyrrhiza polysaccharide (GPS) against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hepatotoxicity in Jian carp, the fish were fed diets containing GPS at doses of 0.1, 0.5 and 1.0g/kg for 60days before an intraperitoneal injection of 0.6μg/kg TCDD at a volume of 0.05mL/10g body weight. At 72hr post-injection, blood and liver samples were taken for biochemical analysis and the fish liver samples were used for the preparation of pathological slices. The results showed that increases in alanine aminotransferase (GPT), aspartate aminotransferase (GOT), lactate dehydrogenase (LDH), and alkaline phosphatase (AKP) in serum induced by TCDD were significantly inhibited by pre-treatment with 1.0g/kg GPS. Following the 1.0g/kg GPS pre-treatment, total protein (TP), albumin (Alb), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activities in liver tissue increased significantly, malondialdehyde (MDA) formation (P<0.05 or P<0.01) was significantly inhibited, and the expression of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor 2 (AHR2) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) mRNA (P<0.05) was significantly enhanced. Histological observations on fish liver were obtained by preparing paraffin tissue sections via HE staining, and the results showed that histological changes were obviously reduced by 0.5 and 1.0g/kg GPS. GPS significantly reduced liver tissue damage caused by TCDD. Overall, these results proved the hepatoprotective effect of GPS in protecting against fish liver injury induced by TCDD, and supported the use of GPS (1.0g/kg) as a hepatoprotective and antioxidant agent in fish.

Antioxidative, anti-inflammatory and hepatoprotective effects of resveratrol on oxidative stress-induced liver damage in tilapia (Oreochromis niloticus)

Resveratrol, a dietary polyphenol, has been shown to exert antioxidation, hepatoprotection, anti-inflammation and immunostimulation. However, the effects and underlying mechanism of resveratrol on liver injury in fish are still unclear. In the present study, we investigated the potential protective effects and mechanism of resveratrol on oxidative stress-induced liver damage in tilapia. Fish were fed diet containing four doses of resveratrol (0, 0.1, 0.3, and 0.6 g/kg diet) for 60 days, and then given an intraperitoneal injection of H2O2 or saline. The results showed that administration of resveratrol significantly ameliorated H2O2-induced liver injury. In serum and liver, resveratrol treatment suppressed the oxidative stress, as evidenced by the decline of lipid peroxidation level and increase of antioxidant activity. Resveratrol also activated erythroid 2-related factor 2 (Nrf2) signaling pathway and enhanced the heme oxygenase 1 (HO-1), NAD(P) H:quinone oxidoreductase 1 (NQO-1), glutathione S-transferase (GST) mRNA levels. Meanwhile, resveratrol treatment repressed TLR2-Myd88-NF-κB signaling pathway to decrease the inflammatory response in H2O2-induced liver injury as evidenced by the lower interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-8 mRNA levels and higher IL-10 mRNA level. Moreover, resveratrol treatment attenuated immunotoxicity in liver of H2O2-treated fish, accompanied by upregulation of hepcidin (HEP), complement 3 (C3) and lysozyme (LZM) mRNA levels. Overall results suggested that the protection of resveratrol on H2O2-induced liver injury, inflammation and immunotoxicity was due to its antioxidant property and its ability to modulate the Nrf2 and TLR2-Myd88-NF-κB signaling pathways.