ObjectiveTo investigate the protective effect of hesperdin (HDN) on acetaminophen (APAP)-induced acute liver injury in mice. MethodsForty-eight male BALB/c mice were randomly divided into six groups:normal group, model group, HDN (the doses respectively were 500, 250 and 125 mg/kg) group and bifendate group. The HDN group was separately intragastrically given different doses of hesperidin for ten days. The bifendate group was given bifendate. Acute liver injury was induced by injecting APAP (150 mg/kg) in all mice except those in the normal group. After 16 hours, all mice were sacrificed. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The contents of glutathione (GSH) and malondialdehyde (MDA) in liver homogenates were determined. Pathological changes in hepatic tissue were observed under an optical microscope. The expression of high mobility group protein B1 (HMGB1) in hepatic tissue was measured by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. ResultsHDN could significantly reduce serum ALT, AST, liver homogenate MDA levels, improve liver tissue GSH activity and the liver injury was lightened. By RT-PCR and immunohistochemistry, it showed that HDN could inhibit the releasing and expression of HMGB1. ConclusionHDN protects mice from acetaminophen-induced liver injury possibly via mechanisms related to inhibition of the expression and releasing of HMGB1.
Objective To investigate the protective effect of 4-phenylbutyric acid (PBA) on liver injury induced by severe acute pancreatitis (SAP) in rats and its possible mechanism. Methods Twenty-four SPF adult male Sprague Dawley rats were randomly divided into three groups: shame operation group (SO group,n=8), SAP group (n=8), and PBA group (n=8). SAP model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) in biliopancreatic duct in SAP group and PBA group. PBA solution (50 mg/kg) was administeredvia intraperitoneal injection for 3 days prior to establishing models in PBA group. Rats were injected equivalent saline solution instead of PBA solution in SAP group and SO group. All rats were sacrificed at 12 h after modeling. Blood samples were collected by inferior vena cava puncture, and serum levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate transaminase (AST) were measured using a fully automatic chemistry analyzer. The head of pancreas and right lobe of hepatic tissues were harvested and pathological examination was observed under the light microscope. Expressions of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and Caspase-3 in hepatic tissues were evaluated by immunohistochemistry assay. Results Compared with SO group, the serum levels of AMY, ALT and AST were significantly increased in SAP group (P＜0.05). The serum levels of ALT and AST in PBA group were significantly lower than those in SAP group (P＜0.05). There was no difference of the serum levels of AMY between in PBA group and SAP group (P＞0.05). Compared with SO group, the damages of the pancreas and liver tissues and the expressions of GRP78, CHOP and Caspase-3 in hepatic tissues were significantly increased in SAP group (P＜0.05). And the above indices in PBA group were significantly decreased when compared with SAP group. Conclusions PBA can alleviate severe acute pancreatitis-induced liver injury, and the mechanism may be associated with inhibition of endoplasmic reticulum stress (ERS) and reduction of hepatocyte apoptosis.
Objective To assess the effect of pregnant rat adipose-derived stem cells (ADSCs) on repair of acute liver injury. Methods ADSCs were isolated from 18-week pregnant Sprague Dawley rats and were identified by flow cytometry. Twenty Sprague Dawley rats were randomly divided into groups A, B, C, and D (n=5); rats in group A were not treated as normal controls; rats in groups B, C, and D were injected intraperitoneally with CCl4 to establish the acute liver injury model. At 2 hours after modeling, DPBS, 0.1 mL normal rat ADSCs (2×106cells/mL), and pregnant rat ADSCs (2×106cells/mL) were injected into the spleen in groups A, C, and D respectively; rats in group B was not treated. After 7 days, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartic acid transaminase (AST), albumin (ALB), and total protein (TP) in serum were measured. The liver tissue sections were stained with HE. The expressions of Ki67, alpha-fetoprotein (AFP), and ALB were measured by immunohistochemistry. Results The serum levels of TBIL, ALT, and AST in group B were significantly higher than those in groups A, C, and D (P<0.05), but ALB and TP were significantly lower than those in groups A, C, and D (P<0.05). The levels of TBIL, ALT, and AST were significantly higher in groups C and D than group A, and in group C than group D (P<0.05). There was no significant difference in serum levels of ALB among groups A, C, and D (P>0.05). The serum level of TP in groups C and D was significantly lower than that in group A (P<0.05), but no significant difference was found between group C and group D (P>0.05). HE staining showed that the liver tissue of group A had clear structure; the cells arranged neatly with uniform size. The hepatocytes in group B showed obvious edema, disorderly arrangement, dot necrosis in liver lobules, and diffuse infiltration of inflammatory cells. In groups C and D, the inflammation and hepatocellular necrosis were obviously reduced when compared with group B, and the number of vacuoles caused by dilation of mitochondria and rough endoplasmic reticulum was decreased; especially in group D, improvement of liver injury was more effective. The Ki67 positive cell rate was significantly higher in groups C and D than groups A and B (P<0.05), in group B than group A (P<0.05), and in group D than group C (P<0.05). There was no expression of AFP in groups A and B, but positive expression was observed in groups C and D, and AFP positive cell rate of group D was significantly higher than that of group C (t=3.006,P=0.017). ALB expression was significantly higher in groups C and D than groups A and B (P<0.05), and in group D than group C (P<0.05). Conclusion Pregnant rat ADSCs could promote repair of liver injury induced by CCl4.
Objective To evaluate the association between N-acetyltransferase 2 (NAT2) gene polymorphisms and the risk of antituberculosis drug-induced liver injury (ATDILI). Methods We searched the PubMed, Embase, Wanfang, China National Knowledge Internet and VIP databases to find case-control studies, with the last updated search being performed on June 2017. Odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the strength of association. Results A total of 29 studies, involving 1 382 cases and 5 967 controls were included. The results of the Meta-analysis indicated that NAT2 slow acetylators were associated with increased risk of ATDILI compared with fast and intermediate acetylators [OR=3.08, 95%CI (2.44, 3.88), P<0.000 01]. Similar results were also found in subgroup analysis when stratified by ethnicity, isoniazid dosage and diagnostic criteria of ATDILI. Conclusion Individuals with NAT2 slow acetylators may have increased risk of ATDILI.
ObjectiveTo summarize the protective effect of peroxisome proliferator-activated receptor-beta (PPAR-β) in sepsis-induced liver injury and the mechanism, and to provide new ideas for the prevention and treatment of sepsis-induced liver injury.MethodRelevant literatures about protective effect of PPAR-β in sepsis-induced liver injury were collected and reviewed.ResultsPPAR-β played an important role in cell survival, anti-inflammatory, and anti-oxidation. It acted on a variety of pathophysiological processes, could reduce the activation of inflammatory factors, reduce the production of oxygen free radicals, and inhibit the expression of apoptotic proteins, as well as played an important role in anti-inflammatory, anti-oxidative, and anti-apoptotic.ConclusionPPAR-β can inhibit the activation of NF-κB, reduce the release of inflammatory factors, reduce apoptosis, and reduce liver injury by antioxidation, thereby reducing the mortality of sepsis-induced liver injury.
ObjectiveTo explore the relationship between hexokinase domain-containing protein 1 (HKDC-1) single nucleotide polymorphism (SNP) and first-line anti-tuberculosis drug-induced liver injury (ATDILI) in tuberculosis patients in western China.MethodsFrom November 2016 to April 2018, 746 tuberculosis patients treated in West China Hospital of Sichuan University were collected and divided into ATDILI group and non-ATDILI group according to the liver function indicators. DNA was extracted by QIAamp® DNA Blood Mini Kit (Qiagen, Germany). Seven SNPs of the HKDC-1 gene were genotyped by high-throughput genotyping technique and the differences between the two groups were compared.ResultsThere were 118 ATDILI and 628 non-ATDILI cases enrolled in this study. In clinical symptoms, the differences in incidences of fever and weight loss between the two groups were statistically significant (P=0.004, 0.024). The C allele at rs906219 was associated with low susceptibility to ATDILI [odds ratio (OR)=0.737, 95% confidence interval (CI) (0.556, 0.957), P=0.033], and the additive model and dominant model showed that CC/CA genotype had a lower risk of ATDILI than AA genotype [CC vs. AA: OR=0.563, 95%CI (0.325, 0.976), P=0.039; CC+CA vs. AA: OR=0.533, 95%CI (0.348, 0.817), P=0.004].ConclusionThe SNP of rs906219 in HKDC-1 is correlated with ATDILI occurrence in tuberculosis patients in western China, which provides clues for personalized anti-tuberculosis treatment.
ObjectiveTo explore the protective effects of abdominal paracentesis drainage (APD) on pancreatitis-associated liver injury in the early phase of severe acute pancreatitis (SAP). MethodsOne hundred and fourteen consecutive patients with SAP, admitted to the General Hospital of Western Theater Command from January 2015 to January 2021, were included in this retrospective study. The patients were divided into the APD group (n=61) and the non-APD group (n=53) based on whether they underwent APD treatment within 72 h of admission. The variables including baseline data, liverfunction tests, inflammation indexes, severity scores and other variables of the two groups were statistically analyzed. ResultsThe hospital mortality in the APD group was lower than that in the non-APD group (8.2% vs. 22.6%, P=0.031). These severity scores (including APACHE Ⅱ score, Ranson score and modified Marshall score) and inflammation indexes (including C-reactive protein, interleukin-6, interleukin-1 and tumor necrosis factor-α) in the APD group were all lower than those in the non-APD group (P＜0.05). In terms of liver function related indexes, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL), and direct bilirubin (DBIL) after treatment in both two groups were significantly lower than those before treatment (P＜0.05). The levels of ALT, AST, TBIL and DBIL after treatment in the APD group were lower than those in the non-APD group (P＜0.05), and the levels of prealbumin and albumin after treatment in the APD group were higher than those in the non-APD group (P＜0.05), but there were no significant differences in the levels of alkaline phosphatase, GGT and 5′ -nucleotidase after treatment in the two group (P＞0.05). ConclusionFor SAP patients with ascitic fluid, application of APD can attenuate liver injury and improve liver function in the early stage of SAP.
ObjectiveTo summarize the mechanism and research progress of ferroptosis in acute liver injury. MethodThe domestic and foreign literatures related of ferroptosis and acute liver injury were searched and reviewed. ResultsFerroptosis was a newly identified form of iron-dependent cell death. The loss of lipid peroxidation repair activity of glutathione peroxidase 4, the presence of redox active iron and the oxidation of phospholipids containing polyunsaturated fatty acids were considered to be distinctive features of ferroptosis. At present, the research on the regulation of ferroptosis genes involved common liver diseases, including drug-induced liver injury, hepatocellular carcinoma, liver fibrosis, liver ischemia-reperfusion injury, liver failure, nonalcoholic fatty liver and so on. Based on the high correlation between ferroptosis and acute liver injury, chemical therapy targeting ferroptosis could provide individualized treatment for patients with acute liver injury in the future. ConclusionsThe ferroptosis plays a critical role in governing various cellular processes and downstream effects. Its aberrant expression contributes to the development and advancement of acute liver injury through diverse mechanisms. Thoroughly exploring the involvement of the ferroptosis in acute liver injury is of utmost significance, as it holds the potential to unveil novel therapeutic targets for effective management of acute liver injury.
ObjectiveTo understand the latest development in lineage tracing techniques and their applications in the study of liver regeneration mechanisms. MethodA review of domestic and international literature on the application of lineage tracing techniques in liver regeneration was conducted. ResultsA variety of more reliable and advanced lineage tracing techniques had been developed, such as single-cell RNA sequencing, DNA barcode technology, etc., providing powerful tools for a deeper understanding of the mechanisms of liver regeneration. The marked progress had been made in identifying the origins of liver regeneration cells, identifying liver regeneration areas, and studying the mechanisms of liver regeneration after injury. The lineage tracing techniques help to understand the position and function of different types of liver cells within the liver structure, revealing the regenerative potential and contribution of different subpopulations of liver cells. Moreover, these techniques had supported the phenomenon of transdifferentiation between the hepatocytes and the bile duct cells under chronic liver injury conditions, aiding in understanding the specific roles of key signaling pathways in liver regeneration, such as Wnt/β-catenin, Hippo/YAP, and Notch signaling pathways.ConclusionsAlthough lineage tracing techniques have made marked progress in liver regeneration research, liver regeneration is a complex and important physiological process, and the technique still has limitations, such as challenges in marker specificity, longer research cycles and higher costs, potential limitations in translating from animal models to human clinical applications, inability to solve all questions about liver regeneration mechanisms, and ethical and legal issues. Therefore, more in-depth and comprehensive research is still needed to reveal more details of liver regeneration mechanism.