The prognostic evaluation of ALBI score in endoscopic treatment of esophagogastric varices hemorrhage in liver cirrhosis.

To analyze the independent risk factors for recurrent bleeding and death within 1 year after endoscopic treatment of esophagogastric varices hemorrhage (EGVB) in patients with liver cirrhosis, and to validate the predictive value of ALBI score for recurrent bleeding and death within 1 year after endoscopic treatment of EGVB in patients with liver cirrhosis. A total of 338 patients with EGVB who received endoscopic treatment for the first time in the Department of Gastroenterology, First Affiliated Hospital of Nanchang University from January 1, 2016 to March 1, 2020 were selected. A database was established to analyze the patients' demographic data, surgical variables and postoperative outcomes. All patients were contacted and followed up to verify the predictive value of ALBI score for recurrent bleeding and mortality. 130 patients had rebleeding within 1 year after surgery (38.5%). 66 patients died within 1 year after surgery (19.5%). Patients with ALBI grade 3 had significantly higher rebleeding and mortality rates than those with grades 1 and 2. The AUC was used to compare the predictive value of the four scores for rebleeding and mortality within one year after endoscopic surgery. Both ALBI scores had the largest AUC. The ALBI score has certain predictive value for rebleeding and mortality within 1 year after endoscopic therapy in patients with cirrhotic EGVB.

Cap-Assisted Endoscopic Sclerotherapy vs Ligation in the Long-Term Management of Medium Esophageal Varices: A Randomized Trial.

INTRODUCTION: Compared with endoscopic variceal ligation (EVL), cap-assisted endoscopic sclerotherapy (CAES) improves efficacy in the treatment of small esophageal varices (EVs) but has not been evaluated in the management of medium EVs. The aim of this study was to compare CAES with EVL in the long-term management of patients exhibiting cirrhosis with medium EVs and a history of esophageal variceal bleeding (EVB), with respect to variceal eradication and recurrence, adverse events, rebleeding, and survival. METHODS: Cirrhotic patients with medium EVs and a history of EVB were divided randomly into EVL and CAES groups. EVL or CAES was repeated each month until variceal eradication. Lauromacrogol was used as a sclerosant. Patients were followed up until 1 year after eradication. RESULTS: In total, 240 patients (age: 51.1 ± 10.0 years; men: 70.8%) were included and randomized to the EVL and CAES groups. The recurrence rate of EVs was much lower in the CAES group than in the EVL group (13.0% vs 30.7%, P = 0.001). The predictors for variceal recurrence were eradication by EVL (hazard ratio [HR]: 2.37, P = 0.04), achievement of complete eradication (HR: 0.27, P < 0.001), and nonselective ß-blocker response (HR: 0.32, P = 0.003). There was no significant difference in the rates of eradication, rebleeding, requirement for alternative therapy, and mortality or the incidence of complications between groups. DISCUSSION: CAES reduces the recurrence rate of EVs with comparable safety to that of EVL in the long-term management of patients presenting cirrhosis with medium EVs and a history of EVB.

High-throughput screening identified mitoxantrone to induce death of hepatocellular carcinoma cells with autophagy involvement.

The use of highly efficient high-throughput screening (HTS) platform has recently gained more attention as a plausible approach to identify de novo therapeutic application potential of conventional anti-tumor drugs for cancer treatments. In this study, we used hepatocellular carcinoma (HCC) cells as models to identify cytotoxic compounds by HTS. To identify cytotoxic compounds for potential HCC treatments, 3271 compounds from three well established small molecule libraries were screened against HCC cell lines. Thirty-two small molecules were identified from the primary screen to induce cell death. Particularly, mitoxantrone (MTX), which is an established antineoplastic drug, significantly and specifically inhibited the growth and proliferation of HCC cells in vitro. Mechanistic studies of LC3-II, p62 and phosphorylation of p70S6K in HepG2 cells revealed that MTX treatment induced mTOR-dependent autophagy activation, which was further confirmed by the autophagic flux assay using lysosomal inhibitor chloroquine (CQ). In the combined treatment of MTX and CQ, where autophagy was inhibited by CQ, the elevations of cleaved Caspase-3 and PARP were observed, indicating the enhanced apoptosis in HepG2 cells. Taken together, we hypothesize that MTX-induced autophagy plays an pro-survival role in HCC treatment. Combined treatment with autophagy inhibitor may combat the chemo-resistance of HCC to MTX treatment and therefore deserves future clinical investment.

Autophagy inhibition enhanced 5­FU­induced cell death in human gastric carcinoma BGC­823 cells.

The exact molecular mechanism of 5-fluorouracil (5-FU) in human gastric cancer cells remains to be elucidated. Cultured BGC­823 human gastric carcinoma and AGS cell lines were treated with 5­FU. Autophagosome formation was investigated through multiple approaches, including the quantification of green fluorescent protein­microtubule­associated protein 1A/1B­light chain 3 (LC3) puncta, LC3 conversion and electron microscopy observations. Additionally, autophagy was inhibited using 3­methyladenine (3­MA) and beclin­1 ablation, to determine its role in 5­FU­mediated cell death. In addition, the present study assessed alterations in sirtuin expression following 5­FU treatment with reverse transcription­quantitative polymerase chain reaction. 5­FU treatment induced apoptosis and inhibited proliferation in BGC­823 and AGS gastric cancer cells. It is of note that the 5­FU treatment only promoted autophagy in BGC­823 cells. Additionally, inhibition of autophagy by either 3­MA or beclin­1 ablation increased 5­FU­induced cell death in BGC­823 cells. The present study quantified changes in sirtuin (SIRT1, SIRT3, SIRT5, and SIRT6) expression following 5­FU treatment and using a specific inhibitor, sirtinol, the present study investigated their involvement in 5­FU­mediated autophagy. Autophagy inhibition through manipulation of sirtuin proteins may increase the therapeutic efficacy of the 5­FU chemotherapeutic drug against gastric carcinoma.

Duodenal variceal bleeding secondary to idiopathic portal hypertension treated with transjugular intra-hepatic porto-systemic shunt plus embolization: A case report.

BACKGROUND: Duodenal varices are a lesser-known complication with non-cirrhotic portal hypertension. We report a circuitous route from missed diagnosis of duodenal varices to correction. An extremely rare case of duodenal variceal bleeding secondary to idiopathic portal hypertension (IPH) is expounded in this study, which was controlled by transjugular intra-hepatic porto-systemic shunt (TIPS) plus embolization. CASE SUMMARY: A 46-year-old woman with anemia for two years was frequently admitted to the local hospital. Upon examination, anemia was attributed to gastrointestinal tract bleeding, which resulted from duodenal variceal bleeding detected by repeated esophagogastroduodenoscopy. At the end of a complete workup, IPH leading to duodenal varices was diagnosed. Portal venography revealed that the remarked duodenal varices originated from the proximal superior mesenteric vein. TIPS plus embolization with coils and Histoacryl was performed to obliterate the rupture of duodenal varices. The anemia resolved, and the duodenal varices completely vanished by 2 mo after the initial operation. CONCLUSION: TIPS plus embolization may be more appropriate to treat the bleeding of large duodenal varices.

Senescence-associated Long Non-coding RNA (SALNR) Delays Oncogene-induced Senescence through NF90 Regulation.

Long non-coding RNAs (lncRNAs) have recently emerged as key players in many physiologic and pathologic processes. Although many lncRNAs have been identified, few lncRNAs have been characterized functionally in aging. In this study, we used human fibroblast cells to investigate genome-wide lncRNA expression during cellular senescence. We identified 968 down-regulated lncRNAs and 899 up-regulated lncRNAs in senescent cells compared with young cells. Among these lncRNAs, we characterized a senescence-associated lncRNA (SALNR), whose expression was reduced during cellular senescence and in premalignant colon adenomas. Overexpression of SALNR delayed cellular senescence in fibroblast cells. Furthermore, we found that SALNR interacts with NF90 (nuclear factor of activated T-cells, 90 kDa), an RNA-binding protein suppressing miRNA biogenesis. We demonstrated that NF90 is a SALNR downstream target, whose inhibition led to premature senescence and enhanced expressions of senescence-associated miRNAs. Moreover, our data showed that Ras-induced stress promotes NF90 nucleolus translocation and suppresses its ability to suppress senescence-associated miRNA biogenesis, which could be rescued by SALNR overexpression. These data suggest that lncRNA SALNR modulates cellular senescence at least partly through changing NF90 activity.

Lutein prevents alcohol-induced liver disease in rats by modulating oxidative stress and inflammation.

OBJECTIVE: Oxidative stress and inflammation play an important role in pathogenesis of alcohol-induced liver injury. The present study was designed to investigate the protective role of Lutein against alcohol-induced liver injury. TREATMENT: Wistar rats weighing 150-200 g were divided into 3 groups, control, EtOH treatment, Lutein followed by EtOH treatment. Ethanol-treated rats received EtOH [5 g/kg body weight] by gavage every 12 hours for a total of 3 doses. For Lutein pre-treatment, Lutein at a dose of 40 mg/kg was dissolved in the EtOH and gavaged 30 mins before EtOH treatment. METHODS: Oxidative stress markers-(reactive oxygen species, lipid peroxidation, protein carbonyls and sulfhydryls content), liver markers (ALT, AST, ALP and LDH) were determined. Antioxidant enzyme activities and its master regulator Nrf-2 expression were analyzed. Further, inflammatory proteins NF-κB, COX-2, iNOS and inflammatory cytokines (TNF-α, MCP-1, IL-1ß, IL-6) were analyzed. RESULTS: The results showed significant decrease in oxidative stress markers and liver markers in the lutein pre-treatment. Lutein treatment down regulated inflammatory proteins and cytokines with concomitant up regulation in Nrf-2 levels and antioxidant enzymic activities. CONCLUSION: The present study showed that Lutein treatment exerted potent antioxidant and anti-inflammatory property and offered significant cytoprotection against alcohol-induced liver injury.

Involvement of ß-catenin in matrine-induced autophagy and apoptosis in WB-F344 cells.

Matrine, one of the main components extracted from Sophora flavescens, has exhibited pharmacological effects on the differentiation in rat liver oval cells. However, its function and mechanism have not yet been fully elucidated. To further investigate them, an in vitro model was established using a rat liver oval cell line called WB-F344 and treated with matrine. Initially, a significant increase in the number of monodansylcadaverine-positive cells and in the levels of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, which is a specific marker for detecting autophagy, was observed in matrine-treated cells. This indicated that autophagy was stimulated by matrine, which was further confirmed by transmission electron microscopy. Additionally, the apoptotic oval cells were easily detected under matrine treatment using an Annexin-V-fluorescein isothiocyanate/propidium iodide assay, indicating that autophagy and apoptosis were synchronously induced by matrine. A decrease in B-cell lymphoma (Bcl-2) mRNA expression, but an increase in Bcl2-associated X protein (Bax) mRNA expression were observed in matrine-treated cells, which led to an upregulation of the Bax/Bcl-2 ratio, a molecular marker for determining the extent of apoptosis. Next, the molecular mechanism of matrine-induced autophagy and apoptosis was analyzed in WB-F344 cells. ß-catenin degradation was downregulated by matrine and rapamycin, a foregone chemical agonist of autophagy, whereas it was upregulated by 3-methyladenine, a specific inhibitor of autophagy. Additionally, ß-catenin activation induced an increase in LC3-II levels and reversed the Bax/Bcl-2 mRNA ratio under matrine treatment, whereas inhibition of ß-catenin by RNA interference induced a decrease of the LC3-II amount and of the Bax/Bcl-2 mRNA ratio. Finally, matrine treatment attenuated p53; however, with little or no change in LC3-II levels, but a decrease in ß-catenin levels occurred in WB-F344 cells upon treatment with pifithrin-α, a chemical inhibitor of p53, revealing that p53, interfering with ß-catenin, may not be involved in matrine-induced autophagy in WB-F344 cells. These results demonstrate that ß-catenin is involved in matrine-induced autophagy and apoptosis in WB-F344 cells, while ß-catenin is negatively regulated by autophagy and positively by p53, indicating that ß-catenin may be involved in the crosstalk between autophagy and apoptosis in WB-F344 cells.

Blocking autophagic flux enhances matrine-induced apoptosis in human hepatoma cells.

Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V-FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

CSTP1, a novel protein phosphatase, blocks cell cycle, promotes cell apoptosis, and suppresses tumor growth of bladder cancer by directly dephosphorylating Akt at Ser473 site.

Akt/protein kinase B is a pivotal component downstream of phosphatidylinositol 3-kinase (PI3K) pathway, whose activity regulates the balance between cell survival and apoptosis. Phosphorylation of Akt occurs at two key sites either at Thr308 site in the activation loop or at Ser473 site in the hydrophobic motif. The phosphorylated form of Akt (pAkt) is activated to promote cell survival. The mechanisms of pAkt dephosphorylation and how the signal transduction of Akt pathway is terminated are still largely unknown. In this study, we identified a novel protein phosphatase CSTP1(complete s transactivated protein 1), which interacts and dephosphorylates Akt specifically at Ser473 site in vivo and in vitro, blocks cell cycle progression and promotes cell apoptosis. The effects of CSTP1 on cell survival and cell cycle were abrogated by depletion of phosphatase domain of CSTP1 or by expression of a constitutively active form of Akt (S473D), suggesting Ser473 site of Akt as a primary cellular target of CSTP1. Expression profile analysis showed that CSTP1 expression is selectively down-regulated in non-invasive bladder cancer tissues and over-expression of CSTP1 suppressed the size of tumors in nude mice. Kaplan-Meier curves revealed that decreased expression of CSTP1 implicated significantly reduced recurrence-free survival in patients suffered from non-invasive bladder cancers.

The mitogen-inducible gene-6 is involved in regulation of cellular senescence in normal diploid fibroblasts.

BACKGROUND INFORMATION: The mitogen-inducible gene-6 (Mig-6) is a non-kinase scaffolding adaptor protein. It has been shown that Mig-6 may play important roles in regulating stress response, maintaining homeostasis and functioning as a tumour suppressor. In this study, we investigated the role of Mig-6 in cellular senescence. RESULTS: Our results showed that Mig-6 is up-regulated during the senescence process. Functional analysis indicated that cells over-expressing Mig-6 have reduced DNA synthesis and showed the signs of senescence. Knockdown of Mig-6 delayed the initiation of Ras-induced cellular senescence. These results suggest that the increase of Mig-6 expression contributes to establishment of cellular senescence. Furthermore, our results showed that Mig-6 induction of senescence is related to its inhibition of EGF receptor (EGFR)/Erb B signalling. Subsequent analysis of the mechanism responsible for the up-regulation of its expression showed that FOXO3A transcriptionally up-regulates Mig-6 expression via directly binding to the FOXO response element in Mig-6 5'-flanking regulatory sequences. CONCLUSIONS: Mig-6 induces premature senescence via functioning in regulation of cellular senescence in normal diploid fibroblasts.

Nifedipine induced autophagy through Beclin1 and mTOR pathway in endometrial carcinoma cells.

BACKGROUND: Endometrial carcinoma is one of the most common female tract genital malignant tumors. Nifedipine, an L-type calcium channel antagonist can inhibit cell proliferation of carcinomas. Recent studies indicated that a rise in the free cytosolic calcium ([Ca(2+)](c)) was a potent inducer of autophagy. Here, we investigated the relationship between nifedipine and autophagy in Hec-1A cells. METHODS: Cells were cultured with nifedipine (10 µmol/L) and harvested at different times for counting cell number. MTT assay was applied to evaluate the cell viability and transwell assay to reveal cell migration. Apoptotic cells were detected with annexin V/PI assay. Then cells were treated with 3-methyladenine (3-MA) (2.5 mmol/L) for 0, 5, 15, 30, 60, and 120 minutes and the expression of the L-type calcium channel alpha1D (Cav1.3) protein was detected. At last, cells were cultured and assigned to four groups with different treatment: untreated (control group), 10 µmol/L nifedipine (N group), 2.5 mmol/L 3-MA (3-MA group), and 10 µmol/L nifedipine plus 2.5 mmol/L 3-MA (N+3MA group). Autophagy was detected with GFP-LC3 modulation by fluorescent microscopy, and expression of the autophagy-associated proteins (LC3, Beclin1 and P70s6K) by Western blotting and monodansylcadaverine (MDC) labeled visualization. RESULTS: Proliferation of Hec-1A cells was obviously suppressed by nifedipine compared with that of the untreated cells for 24, 48, and 96 hours (P = 0.000 for each day). The suppression of migration ability of the nifedipine-treated cells (94.0 ± 8.2) was significantly different from that of the untreated cells (160.00 ± 9.50, P = 0.021). The level of early period cell apoptosis induced by nifedipine was (2.21 ± 0.19)%, which was (2.90 ± 0.13)% in control group (P = 0.052), whereas the late period apoptosis level reached (10.38 ± 0.96)% and (4.40 ± 0.60)% (P = 0.020), respectively. The 3-MA group induced a slight increase in the Cav1.3 levels within 15 minutes, but significantly attenuated the Cav1.3 levels after 30 minutes. There were more autophagic vacuoles labeled by MDC in the N group (20.63 ± 3.36) than the control group (6.29 ± 0.16, P = 0.015). GFP-LC3 localization revealed that the LC3 levels of cells in 3-MA group, N+3MA group, 3-MA group were 2.80 ± 0.29, 2.30 ± 0.17, and 1.80 ± 0.21, respectively. Cells in the N group showed significant augmentation of autophagy (P < 0.05). Western blotting analysis confirmed the down-regulation of LC3 levels in 3-MA group (0.85 ± 0.21) and N+3MA group (1.21 ± 0.12) compared with nifedipine treatment (2.64 ± 0.15, P < 0.05). The annexin-V-FITC/PI assay showed that the level of early period cell apoptosis induced in the N+3-MA group ((11.22 ± 0.91)%) differed significantly from that of the control group ((2.51 ± 0.70)%) and N group ((3.47 ± 0.39)%). Similarly, the late period level of the N+3-MA group ((55.19 ± 2.51)%) differed significantly from that of the control group ((15.81 ± 1.36)%) and the N group ((22.09 ± 2.48)%, P < 0.05). The down-regulated expression of P70s6k and up-regulated expression of the Beclin1 revealed significant differences between the N+3-MA group and control group (P = 0.025; Beclin1: P = 0.015). CONCLUSIONS: Proliferation and migration in vitro of endometrial carcinoma Hec-1A cells are significantly suppressed by nifedipine. The nifedipine leads autophagy to oppose Hec-1A cells apoptosis. Autophagy inhibition by 3-MA leads down-regulation of Cav1.3 and enhances nifedipine-induced cell death. The nifedipine-induced autophagy is linked to Beclin1 and mTOR pathways.

Autophagy in premature senescent cells is activated via AMPK pathway.

Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. In this study, we show that the activity of autophagy increases in H(2)O(2) or RasV12-induced senescent fibroblasts. Inhibiting autophagy promotes cell apoptosis in senescent cells, suggesting that autophagy activation plays a cytoprotective role. Furthermore, our data indicate that the increase of autophagy in senescent cells is linked to the activation of transcription factor FoxO3A, which blocks ATP generation by transcriptionally up-regulating the expression of PDK4, an inhibitor of pyruvate dehydrogenase complex, thus leading to AMPK activation and mTOR inhibition. These findings suggest a novel mechanism by which FoxO3A factors can activate autophagy via metabolic alteration.

Autophagy inhibition enhances etoposide-induced cell death in human hepatoma G2 cells.

Induction of autophagy usually acts as a survival mechanism of cancer cells in response to chemotherapy. However, the function and molecular mechanism of autophagy in human hepatoma cells under drug treatment is still not clear. To address this issue, we established an experimental model in which HepG2 cells were treated with etoposide, a widely used anticancer agent. We demonstrate the etoposide-induced accumulation of GFP-LC3 dots by fluorescent microscopy, the up-regulation of LC3-II protein expression by Western blotting and the increased number of autophagic vacuoles by electron microscopy, confirming the activation of autophagy by etoposide in HepG2 cells. Inhibition of autophagy by either 3-methyladenine (3MA) or beclin-1 small interfering RNA enhanced etoposide-induced cell death. Furthermore, activation of p53 and AMPK was detected in etoposide-treated cells and inhibition of AMPK triggered apoptosis through suppression of autophagy. On the other hand, inactivation of p53 promoted cell survival through augmentation of autophagy. Collectively, these findings indicate that etoposide-induced autophagy promotes hepatoma cell adaptation and survival, and that autophagy inhibition improves the chemotherapeutic effect of etoposide. Moreover, AMPK activation is clearly associated with etoposide-induced autophagy. We conclude that manipulation of AMPK may be a promising approach of adjuvant chemotherapy for hepatocellular carcinoma.

[Effect of baicalin on liver fatty acid binding protein in oxidative stress model in vitro].

OBJECTIVE: To investigate the effect of baicalin on liver fatty acid binding protein in oxidative stress model in vitro. METHODS: (1) Cellular oxidative stress in vitro was induced by incubating cells with 400µmol/L hydrogen peroxide (H2O2) for 20 minutes at 37 degrees C in the dark. After Chang liver cell line was treated with different dose of baicalin for 24, 48 and 72 hours. MTT assay was employed to detect cell viability, and then the hydrogen peroxide (TC50) of the different dose of baicalin was calculated. (2) Based on MTT assay, cells were treated with three different doses of baicalin (25, 50, 100 µmol/L) for 24 and 48 hours before being exposed to 400 µmol/L H2O2 for 20 minutes at 37 degrees C. Then, reactive oxygen species (ROS) assay and activity assays of superoxide dismutase (SOD) and reduced glutathione hormone (GSH) were evaluated. (3) Realtime PCR and Western blotting were applied to explore the influence of baicalin on the expression level of L-FABP. (4) One-way ANOVA was used for results statistical analysis. RESULT: (1) MTT assay showed baicalin treatment at 25, 50, 100 µmol/L for 24 and 48 hours was feasible (83.60% ± 3.47%, 72.36% ± 2.18%, 70.16% ± 2.04% for 24 hours; 84.93% ± 3.11%, 76.16% ± 2.45%, 72.72% ± 2.31% for 48 hours, P > 0.05, F = 386.24, 475.92 respectively). Meanwhile, we found by the linear regression model that the median toxic concentration of baicalin for 48 hours was 170.6 µmol/L, and the median toxic concentration of baicalin for 24 hours was 153.2 µmol/L. (2) ROS assay showed dichlorofluorescin in all baicalin-treated cells after stress was significantly reduced (37.0 ± 3.30, 22.90 ± 3.84, 29.60 ± 2.52 for 24 hours respectively, P < 0.05, F = 70.06; 35.77 ± 2.35, 21.80 ± 3.10, 23.87 ± 1.98 for 48 hours respectively, P < 0.05, F = 110.92) as compared with the H2O2-treated cells. Moreover, 50 µmol/L baicalin treatment for 48 hours was the optimal condition against ROS generation (21.80 ± 3.10, P < 0.01, F = 110.92). Furthermore, the activities of intracellular SOD and GSH was increased significantly (51.53 ± 1.91 µg/mg for SOD, P < 0.05, F = 93.81; 49.85 ± 1.45 U/mg for GSH, P < 0.05, F = 92.51). (3) Although realtime PCR analysis indicated 50 µmol/L baicalin treatment for 48 hours could have no changes of the level of L-FABP expression under the oxidative stress condition, western blotting analysis indicated 50 µmol/L baicalin treatment for 48 hours could increase up to about 80% for the level of L-FABP expression. CONCLUSION: Baicalin was suggested to be able to enhance both L-FABP expression and activity of intracellular SOD and GSH, and therefore protected hepatocytes from oxidative stress.