Magnesium isoglycyrrhizinate inhibits inflammatory response through STAT3 pathway to protect remnant liver function

AIM: To investigate the protective effect of magnesium isoglycyrrhizinate(Mg IG) on excessive hepatectomy animal model and its possible mechanism.METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method,in which the left,middle,right upper,and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups,and were injected intraperitoneally with 3 m L saline(control group),30 mg/kg(low-dose group) and 60 mg/kg(high-dose group) of Mg IG,respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl endopeptidase,total bilirubin(TBil),direct bilirubin(DBil),total protein,albumin,blood glucose(Glu),hyper-sensitivity C-reactive protein,prothrombin time(PT),and thrombin time(TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines(IL-1,IL-6,IL-10,and i NOS) was analyzed by ELISA. STAT3 protein and m RNA were analyzed by Western blot and quantitative reversetranscription PCR,respectively.RESULTS: The high-dose group demonstrated a significantly prolonged survival time,compared with both the control and the low-dose groups(22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h,P = 0.018). There were significant differences among the groups in ALT,Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the Mg IG treated groups than in the control group. Both Glu and PT levels were significantly higher in the Mg IG treated groups than in the control group. At 12 h,ALT,AST,TBil,DBil and TT levels showed significant differences between the Mg IG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group,the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10,and a decrease in IL-6. Both STAT3 protein and m RNA levels were significantly lower in the Mg IG treated groups than in the control group at 6 h,12 h,and 18 h after surgery.CONCLUSION: High-dose Mg IG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflam-matory response through inhibition of the STAT3 pathway.

The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics

BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Potential application of neogalactosylalbumin in positron emission tomography evaluation of liver function

AIM To investigate the evaluation of neogalactosylalbumin (NGA) for liver function assessment based on positron emission tomography technology. METHODS Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride (CCl4) at 0.4 ml every 48 h for 42 d. F-18-labeled NGA ([F-18] FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [F-18] FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed. RESULTS The liver function of the fibrosis model mice was significantly impaired by the use of CCl4. In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [F-18] FNGA was found to predominantly accumulate in liver and kidneys in both control group (n = 21) and fibrosis group (n = 23). The liver uptake ability (LUA), peak time (T-p), and uptake rate (LUR) of [F-18] FNGA between healthy liver (n = 8) and fibrosis liver (n = 10) were significantly different (P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level (TP) (P < 0.05). T-p was significantly correlated with both TP and glucose (Glu) concentration (P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration (P < 0.01 and < 0.05, respectively). CONCLUSION [F-18] FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [F-18] FNGA compared to the controls.