Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Comparison of Effect of Euodiae Fructus Processed with Different Proportions of Glycyrrhizae Radix et Rhizoma on Oxidative Stress and Autophagy in Mouse Liver Under Toxic Dose / 中国实验方剂学杂志

ObjectiveTo investigate the principle and scientific connotation of Euodiae Fructus（EF） processed with Glycyrrhizae Radix et Rhizoma（Gly） by comparing the effects of unprocessed products of EF（UEF） and processed products of EF with the different proportions of Gly（GEFs） at toxic doses on oxidative stress and autophagy in the liver of mice. MethodSeventy mice were randomly divided into 7 groups， namely the control group， the UEF group， the group of the processed products of EF without Gly（PEF） and 4 groups of GEFs（the mass ratios of EF to Gly were 100∶3， 100∶6， 100∶12 and 100∶24， respectively， hereinafter referred to as the processed products of EF with the mass ratios of 100∶3， 100∶6， 100∶12 and 100∶24 of Gly）. The mice were given purified water， the decoction of UEF， PEF and GEFs by gavage at a dose of 30 g·kg-1. PEF and GEFs were prepared according to the method under EF in the 2020 edition of Chinese Pharmacopoeia. Levels of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were determined by ultraviolet-visible spectrophotometry， hematoxylin-eosin（HE） staining was used to evaluate the pathological changes of liver tissue， the level of reactive oxygen species（ROS） was detected by fluorescence method， the mRNA expression of heme oxygenase-1（HO-1）， quinone oxidoreductase-1（NQO1）， glutathione-S-transferase 1（GSTA1）， Kelch-like epichlorohydrin-associated protein 1（Keap1） and p62 were measured by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， western blot was used to detect the protein expression of phosphorylated mammal target of rapamycin（p-mTOR）， phosphorylated ribosomal p70 S6 protein kinase（p-p70S6K）， p62， microtubule-associated protein 1 light chain 3Ⅰ（LC3Ⅰ） and LC3Ⅱ. ResultCompared with the control group， after 7 d of administration， the increase in body mass of mice in the UEF group began to slow down and the difference gradually increased， and the liver body index significantly increased（P<0.01）， pathomorphological observation showed that the structure of hepatic lobules was disordered， and local hepatic sinuses were narrowed or disappeared， and there were inflammatory infiltration and local bleeding， the levels of ALT and AST in serum and ROS in liver tissue were significantly increased（P<0.01）， and the expressions of Keap1， HO-1， NQO1， GSTA1， p62 mRNA and p-mTOR， p-p70S6K， p62 protein in liver tissue were significantly decreased（P<0.01）， and LC3Ⅱ/LC3Ⅰ was significantly increased（P<0.01）. Compared with the UEF group， the body mass of mice increased， and the liver body index， the levels of ALT and AST in serum， and the level of ROS in liver tissue all decreased in the groups of PEF and GEFs. Among these groups， only the liver lobules in GEF（100∶6） group were intact， and the size of liver sinuses was close to that in the control group. The mRNA expressions of Keap1， HO-1， NQO1， GSTA1 and p62 in liver tissue showed an overall upward trend in the groups of PEF and GEFs. Among these groups， only the ones of the above mRNA in the GEF（100∶6） group had a significant increase（P<0.05， P<0.01）. The protein expressions of p-mTOR， p-p70S6K， p62 and LC3Ⅱ/LC3Ⅰ had a callback in the groups of PEF and GEFs， of which the protein expressions of p-mTOR， p-p70S6K and LC3Ⅱ/LC3Ⅰ in the GEF（100∶6） group and the expression of p62 protein in the GEF（100∶24） group had the largest callback. Except for p-mTOR protein， other protein expressions were statistically significant（P<0.05， P<0.01）. ConclusionThe hepatotoxicity of EF is closely related to its ability to induce oxidative stress， which leads to pathological autophagy and hepatocyte damage. This ability can be reduced by the processing with different proportions of Gly， especially the ratio of 100∶6.

The effects of silymarin plus glutathione on the prevention of liver ischemia-reperfusion injury

Abstract Liver ischemia-reperfusion (IR) injury is a major clinical trouble encountered in clinical practice. This study aimed to examine the therapeutic effects of silymarin (SM) plus glutathione (GSH) on hepatic IR injury using a rat model of liver IR. Fifty male rats were randomly divided into five groups, each consisting of 10 rats as follows: Sham, IR, SM-IR, GSH-IR and SM plus GSH-IR. All groups except sham were subjected to 30-min ischemia and 24-h reperfusion. The treated groups received 100 mg/kg of SM, GSH and a mixture of SM plus GSH, 60 min prior to the IR. After a period of 24 h, blood and liver samples were collected for biochemical and histopathological evaluations. Pretreatment with SM, GSH and SM plus GSH before hepatic IR significantly decreased IR-induced elevations of aminotransferases, and significantly reduced the histopathological damage scores of the liver in the late phase of IR injury. Moreover, SM plus GSH treatment prior to liver IR significantly suppressed inflammatory process and oxidative stress as demonstrated by attenuations in tumor necrosis factor-α, myeloperoxidase and the thiobarbituric acid-reactive substances. These findings suggest that administration of SM plus GSH prior to liver IR may protect the liver parenchyma from the effects of an IR injury

Effects of cycloastragenol on carbon tetrachloride-induced hepatic fibrosis and glycolysis in mice / 中国药房

OBJECTIVE To study the effects of cy cloastragenol （CAG） on carbon tetrachloride （CCl4）-induced hepatic fibrosis（HF）and glycolysis in mice. METHODS Male ICR mice were randomly divided into blank group ，model group ，CAG low-dose，medium-dose and high-dose groups （60，120，240 mg/kg），with 6 mice in each group. Except that blank group was given olive oil intraperitoneally ，the mice in other groups were intraperitoneally injected with 10％CCl4-olive oil solution （5 mL/kg） three times a week for 8 weeks to induce HF model. From the 4th week after modeling ，mice in each drug group were given corresponding drug solution intragastrically （10 mL/kg），and mice in blank group and model group were given 0.5％ sodium carboxymethyl cellulose solution intragastrically （10 mL/kg），once a day for 4 weeks. During the experiment ，the body weight of mice were weighted ；after last gastrogavage ，the liver weight was weighted and liver indexes of mice were calculated. The changes of hepatic injury indexes [aspartate aminotransferase （AST）， alanine aminotransferase （ALT）]， related indexes of HF [hematoxylin-eosin （HE）staining score ，Masson and Picrosirius red staining collagen volume fraction ，collagen Ⅰ，α-smooth muscle actin （α-SMA）] and related indexes of glycolysis [lactic acid （LD），hexokinase（HK），phosphofructokinase（PFK）， pyruvate kinase （PK）] were all detected. RESULTS Compared with model group ，the collagen deposition and fibrosis of mice in each drug group were reduced ，and the body weights of mice （except for CAG low-dose group ）were increased to some extent （P＜0.05）. Liver indexes ，serum levels of ALT and AST ，HE staining score of liver histopathology ，Masson and Picrosirius red staining collagen volume fraction ，protein expression of collagen Ⅰ and α-SMA，serum content of LD ，the levels of HK ，PFK and PK in serum and hepatic tissues （except for hepatic tissue of CAG low-dose group ）were all decreased significantly （P＜0.05）. CONCLUSIONS CAG can improve HF in mice induced by CCl 4，and reduce the levels of key enzymes and products of glycolysis.

Hepatic injury following umbilical vein catheterization in neonates: a report of seven cases and literature review / 中国小儿急救医学

Objective:To study the clinical characteristics of hepatic injury following umbilical vein catheterization, so as to improve the safety and use of umbilical vein catheterization in the newborn.Methods:Data of infants undergoing umbilical vein catheterization during hospitalization in the neonatology department of the Third Affiliated Hospital of Guangzhou Medical University from Jan 1st, 2015 to Dec 31st, 2019 were collected retrospectively.The clinical characteristics, diagnoses and treatments of the infants with hepatic injury following umbilical vein catheterization were summarized and analyzed.And the relative literature was reviewed.Results:A total of 1 721 infants underwent umbilical vein catheterization, and seven cases(0.4%)had hepatic injury, including six cases of exudative necrosis in the liver and one case of hepatic hematoma.There was no significant difference in gestational age[(31.12±2.64)weeks vs.(30.62±2.75)weeks]or birth weight[(1 493±525)g vs.(1 374±473)g]between hepatic injury group and non-hepatic injury group( P>0.05). Clinically, it was found that the tip position of umbilical vein catheter was below the diaphragm(between the 9th and 11th thoracic vertebrae)in all seven cases.Except one case with no obvious clinical symptoms, the other six cases had clinical symptoms, mainly manifested as abdominal distension, repeated gastric retention, decreased bowel sounds, and additional with shock and anemia in hepatic hematoma.Blood sample tests showed elevated C-reactive protein, white blood cell count and transaminase.X-ray examination revealed cystic translucent shadow in the liver, and ultrasound and/or computed tomography examination showed the lesion in more detail.After removal of the catheter and administration of antibiotic, the hepatic injury recovered gradually. Conclusion:The hepatic injury following umbilical vein catheterization in neonates is not common.The catheter tip under the diaphragm is the main risk factor.And the diagnosis is dependent on imaging examination.

Effects of 5-HMF on glycolipid metabolism and hepatic function in mice with diabetes and hepatic injury / 预防医学

Objective@#To observe the effect of 5-hudroxymethyl-2-furfural (5-HMF) on glycolipid metabolism and hepatic function in mice with type 2 diabetes mellitus (T2DM) and hepatic injury. @*Methods@#A low, a medium and a high 5-HMF dose group, a model group, and a control group were designed, with ten female ICR mice in each group. The low, medium and high dose group were given 0.27, 0.80 and 2.67 mg/kgbw 5-HMF, respectively, for 12 weeks; while the model group and the control group were given volume controlled deionized water. The model group and three dose groups were fed with high-fat and high-sugar food (36%), and the intraperitoneal injection of alloxan (60 mg/kgbw) was executed in the 10th and 11th week; the control group were fed with normal food. The body weight, blood glucose, blood lipid, and liver function of mice were determined regularly. The livers were stained by periodic acid Schiff and the changes in pathology were observed. @*Results@#Compared with the control group, the serum levels of glucose (GLU), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were significantly higher in the model group (P<0.05). Compared with the model group, the AST level in the low and high 5-HMF dose group, and the LDH level in the low, medium and high 5-HMF dose group, were significantly lower (P<0.05). There were no significant differences in the levels of GLU, total cholesterol, LDL-C, triacylglycerol, HDL-C and ALT between the model group and the three dose groups (P>0.05). Moderate to severe vacuolar degeneration was observed in the model group, while mild vacuolar degeneration was observed in the high dose group. Medium or large amount of hepatic glycogen granules were observed in the high dose group and the model group. @*Conclusion@#Under the conditions of this experiment, 5-HMF does not show any obvious function of reducing blood glucose and lipid in the mice with T2DM and liver injury, but show some protective effects on liver function．

Environmental exposure as a risk-modifying factor in liver diseases: Knowns and unknowns

Liver diseases are considered to predominantly possess an inherited or xenobiotic etiology. However, inheritance drives the ability to appropriately adapt to environmental stressors, and disease is the culmination of a maladaptive response. Thus "pure" genetic and "pure" xenobiotic liver diseases are modified by each other and other factors, identified or unknown. The purpose of this review is to highlight the knowledgebase of environmental exposure as a potential risk modifying agent for the development of liver disease by other causes. This exercise is not to argue that all liver diseases have an environmental component, but to challenge the assumption that the current state of our knowledge is sufficient in all cases to conclusively dismiss this as a possibility. This review also discusses key new tools and approaches that will likely be critical to address this question in the future. Taken together, identifying the key gaps in our understanding is critical for the field to move forward, or at the very least to "know what we don't know."

Study on CYP2E1 gene polymorphism and the relationship between methylation level of its promoter region and liver injury induced by anti-tuberculosis drugs in Mongolian tuberculosis patients in Inner Mongolia / 医学研究生学报

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

Study on CYP2E1 gene polymorphism and the relationship between methylation level of its promoter region and liver injury induced by anti-tuberculosis drugs in Mongolian tuberculosis patients in Inner Mongolia / 医学研究生学报

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

Separation and physicochemical properties of polysaccharides from Morinda officinalis and their effects on human liver cells / 国际药学研究杂志

Objective: To separate the fractions and components of crud polysaccharides MOP-60 and MOP-60-100 from Morinda officinalis, characterize their physicochemical properties and effects on the LO2 cell proliferation as well as on the ConA- and H2O2-induced LO2 cell death. Methods: The five fractions(MOP-60-A, MOP-60-B, MOP-60-100-A, MOP-60-100-B and MOP-60- 100-C)were obtained by column chromatographic separation of MOP-60 or MOP-60-100 on a DEAE-DEAE-cellulose column. A component MOP-60-Ⅰ was obtained by dialysis of MOP-60-A. The further separation and purification of MOP-60-100-B by the Sephadex G-100 column chromatography afforded the other two components MOP-60-100-Ⅰ and MOP-60-100-Ⅱ. The molecular distribution was determined with gel filtration chromatography. The monosaccharide compositions were analyzed with capillary electrophoresis after acid hydrolysis and PMP derivation. The effects of the fractions and components of polysaccharides on the human LO2 liver cell proliferation and on the ConA- and H2O2-induced LO2 cell damage were evaluated by the MTT method. Results: MOP-60-A, MOP-60-100-A and MOP-60-Ⅰ were composed of fructose(fructosan), and the peak relative molecular mass of MOP-60-Ⅰ was 2339. MOP-60-B, MOP-60-100-B, MOP-60-100-C, MOP-60-100-Ⅰ and MOP-60-100-Ⅱ were composed of multiple monosaccharides and heteroglycans. The peak relative molecular mass of MOP-60-100-Ⅰ and MOP-60-100-Ⅱ were 62 828 and 7783, respectively. MOP-60-B, MOP-60-100-B and MOP-60-100-C increased human LO2 hepatocyte proliferation and reduced the ConA-induced LO2 cell death at 250 mg/L(P<0.01, compared to solvent or ConA alone group). MOP-60-100-C also reduced the H2O2-induced LO2 cell death at 100 and 250 mg/L(P<0.05 and P<0.01, compared to H2O2 alone group). Conclusion: The acidic fractions MOP-60-100-B and MOP- 60-100-C from M. officinalis significantly promoted LO2 cell proliferation and inhibited the ConA- and H2O2-induced cell damage in human liver LO2 cells.

Regulatory Effect of Gandou Decoction on Wnt/β-catenin Signaling Pathway in Liver of Wilson Model Copper-loaded Rats / 中国实验方剂学杂志

Objective: To investigate the regulatory effect of Gandou decoction (GDD) on Wnt/β-catenin signaling pathway in hepatic tissue of Wilson disease model copper-loaded rats and its potential mechanism. Method: One hundred and fifteen SD rats were randomly divided into the normal group (n=20) and modeling group. Modeling group was given copper sulfate feed (1 g·kg-1·d-1) and 0.185%copper sulfate solution (0.02 mL·g-1·d-1) for 12 weeks after one week's adaptive feeding, so as to build the copper loaded rats model. After modeling, 95 model rats were randomly divided into model group (n=45), which were fed by modeling method for continuously four weeks; GDD group and penicillamine (PCA) group (n=25 per group). GDD group and PCA group were given GDD(0.4 g·kg-1·d-1) and PCA (0.09 g·kg-1·d-1) by gavage for four weeks. The hepatic tissues of rats in each group were removed after final medication for further research:inductively coupled plasma-atomic emission spectrometry(ICP-AES) was used to detect the content of Cu element in rat livers. Htoxylin eosin(HE) staining was used to detect the pathological changes of rat liver. Immunohistochemistry was used to detect expression of oxidative stress. Western blot was used to detect protein expressions in Wnt/β-catenin of rat livers. Result: Compared with model group, content of Cu element in GDD group was less (PPPβ-catenin, p-glycogen synthase kinase-3β(p-GSK3β),cellular myelocytomatosis oncogene (c-Myc) in GDD and PCA group increased, while p-β-catenin, Dishevelled3, GSK3β protein expressions reduced (PConclusion: GDD can relieve liver damage by promoting excessive copper discharge. GDD decoction can promote the compensatory self-healing of the injured liver tissue by activating Wnt/β-catenin signaling pathway in the hepatic tissue of Wilson disease model copper-loaded rats, so as to reduce the therapeutic effect of hepatocellular injury induced by high copper.

Evaluation of hepatoprotective activity of Syringa oblata leaves ethanol extract with the indicator of glutathione S-transferase A1

Abstract The leaves of Syringa oblata Lindl., Oleaceae, had been extensively used as a folk medicine to treat various infections, heal inflammations, icteric hepatitis and acute mastitis. The study was designed to evaluate the hepatoprotective activity of S. oblata leaves ethanol extract against CCl4-induced hepatotoxicity in primary hepatocytes and mice with the indicator of glutathione S-transferase alpha 1. The hepatoprotective effects of S. oblata leaves ethanol extract were evaluated on the basis of liver histopathology and biochemical parameters as well as hepatic oxidative stress markers. The results showed that CCl4 negatively modulated biochemical parameters and liver antioxidant activities. However, the use of S. oblata leaves ethanol extract restored altered-serum biochemical parameters and liver antioxidant activities in a dose-dependent manner. Importantly, the trends in S-transferase alpha 1 were similar to alanine aminotransferase and aspartate aminotransferase level, and S-transferase alpha 1 was suggested to be a marker for the evaluation of hepatoprotective activity of S. oblata leaves ethanol extract. Histopathological examination showed that CCl4 causes significant hepatic injury relative to control group. The above findings suggested that S. oblata leaves ethanol extract has hepatoprotective effects against CCl4-induced hepatic injury and S-transferase alpha 1 may be an indicator to evaluate the protective effects of S. oblata leaves ethanol extract.

Erythrocyte membrane fatty acid profile & serum cytokine levels in patients with non-alcoholic fatty liver disease

Background & objectives: Fatty acids may affect the expression of genes, and this process is influenced by sex hormones. Cytokines are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), so this study was aimed to assess the association of erythrocyte membrane fatty acids with three cytokines and markers of hepatic injury in NAFLD patients and to explore whether these associations were the same in both sexes. Methods: In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD during the study period. Tumour necrosis factor-? (TNF-?), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), aspartate aminotransferase and alanine aminotransferase were measured in a fasting serum sample, and Fibroscan was conducted for each individual. Gas chromatography was used to measure erythrocyte membrane fatty acids. Univariate and multiple linear regressions were used to analyze data. Results: In men, IL-6 had a significant (P <0.05) positive association with total ?-3 polyunsaturated fatty acids (PUFAs). In women, TNF-? had a significant positive association with total ?-3 (P <0.05) and ?-6 (P <0.01) PUFAs, IL-6 had a significant (P <0.05) positive association with total monounsaturated fatty acids and MCP-1 had a significant positive association with total trans-fatty acids (P <0.05). No significant associations were observed between erythrocyte membrane fatty acids and liver enzymes or Fibroscan report in both sexes. In this study, women were significantly older than men [51 (42.75-55) vs 35.5 (29-52), P <0.01], so the associations were adjusted for age and other confounders. Interpretation & conclusions: Erythrocyte membrane fatty acid profile was not associated with serum liver enzymes or Fibroscan reports in NAFLD patients, but it had significant associations with serum TNF-?, IL-6 and MCP-1 and these associations were probably sex dependent.

Ameliorative effect of Pergularia daemia (Forssk.) Chiov. leaves extract against anti-tuberculosis drugs induced liver injury in rats

Objective:To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia (P. daemia) against anti-tuberculosis drugs (ATDs) induced liver injury.Methods:Wistar albino rats were divided into seven groups of six animal in each. The ATDs and P. daemia extract (100, 200 and 400 mg/kg, p.o.) were conjointly administered for 8 weeks and various biochemical, histoarchitectural, ultrastructural studies were performed.Results:Administration of ATDs significantly increased aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, cholesterol, bilirubin and decreased glucose and albumin level. Increased lipid peroxidation and reduction in glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were found after ATDs exposure. Administration of P. daemia extract maintained serum biochemical indices as well as antioxidant status similar to control and diminished oxidative stress in dose dependent manner. Histological and ultra-structural observations substantiated biochemical findings.Conclusions:P. daemia has therapeutic potential against ATDs induced liver injury and may be of clinical significance after extensive studies.

Propolis modulates cellular biochemistry, antioxidants, cytokine profile, histological and ultra-morphological status against antituberculosis drugs induced hepatic injury

Objective:To evaluate hepatic injury induced by antituberculosis drugs (ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis (bee hive product) against ATDs induced hepatic injury.Methods:The ATDs were administered for 8 weeks as well as propolis extract at three different doses (100, 200, 400 mg/kg) conjointly for 8 weeks in rats. Silymarin (50 mg/kg) was given as positive control. Animals were euthanized after 8 weeks; blood and liver samples were collected to perform various biochemicals, serological and histopathological and ultramorphological studies.Results:Significant increase (P < 0.05) in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglyceride and cholesterol along with reduction in glucose and albumin level were noted after ATDs induced hepatic injury. Significant increase (P < 0.05) in lipid peroxidation, triglyceride, cholesterol and CYP2E1 activity; decline in reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glucose-6-phosphatase dehydrogenase activity were observed after ATDs intoxication. Due to presence of a wide range of flavonoids and polyphenols in propolis extract, its administration reduced hepatic injury and maintained biochemical indices towards control. Histopathological and electron microscopic observations indicated hepatoprotective potential of propolis at cellular level whereas, TNF-α, IL-6 and IGF-1 confirmed therapeutic potential of propolis at molecular level.Conclusions:It can be concluded that propolis possess hepatoprotective potential against ATDs induced hepatic injury that may prove itself as a clinically useful natural product in management of drug induced liver injury.

Effect of bilateral greater splanchnic nerve transection on hepatic injury in dogs with acute necrotizing pancreatitis / 临床肝胆病杂志

ObjectiveTo investigate the effect of bilateral greater splanchnic nerve transection on hepatic injury in dogs with acute necrotizing pancreatitis (ANP). MethodsA total of 24 healthy adult mongrel dogs were randomly divided into sham-operation group (SO group with 8 dogs), ANP model group (ANP group with 8 dogs), and ANP+bilateral greater splanchnic nerve transection group (GSNT group with 8 dogs). Peripheral venous blood samples were collected at 2 hours before surgery and at 12 and 24 hours and 3, 5, and 7 days after surgery to measure the serum levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The dogs were sacrificed at 7 days after surgery, and the pancreatic and hepatic tissues were harvested to observe their pathological changes by visual inspection and under a light microscope. Western blot was used to measure the protein expression of p-NF-κB p65 in liver tissue. A one-way analysis of variance and a repeated-measures analysis of variance were used for comparison between groups, and the least significant difference t-test and wilcoxon rank sum test were used for further comparison between two groups. ResultsAt 2 hours before surgery, there were no significant differences in serum levels of AMY, ALT, and AST between the three groups (P＞0.05). Compared with the SO group, the ANP group and the GSNT group had significant increases in the serum levels of AMY, ALT, and AST, pancreatic and liver pathological scores, and the protein expression of p-NF-κB p65 in liver tissue after surgery (all P＜0.05). After surgery, the GSNT group had significantly lower serum levels of ALT and AST, pancreatic and liver pathological scores, and protein expression of p-NF-κB p65 in liver tissue than the ANP group (all P＜0.05), while there was no significant difference in the serum level of AMY between these two groups (P＞0.05). ConclusionThe activation of NF-κB plays an important role in the progression of ANP in dogs. Bilateral greater splanchnic nerve transection can alleviate liver injury in dogs with ANP, and such a protective effect may be associated with the downregulation of NF-κB activity in the liver.

Protective effect of Ginkgo biloba extract on paracetamol-induced acute hepatic injury in mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism.@*METHODS@#Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg)groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1.@*RESULTS@#Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly(<0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue(<0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue(<0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly(<0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue(<0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue(<0.05). The high-dose of GBE possessed the most obvious treatment effect among them.@*CONCLUSIONS@#GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.

Ameliorative effect of Pergularia daemia (Forssk.) Chiov. leaves extract against anti-tuberculosis drugs induced liver injury in rats

Objective: To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia (P. daemia) against anti-tuberculosis drugs (ATDs) induced liver injury. Methods: Wistar albino rats were divided into seven groups of six animal in each. The ATDs and P. daemia extract (100, 200 and 400 mg/kg, p.o.) were conjointly administered for 8 weeks and various biochemical, histoarchitectural, ultrastructural studies were performed. Results: Administration of ATDs significantly increased aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, cholesterol, bilirubin and decreased glucose and albumin level. Increased lipid peroxidation and reduction in glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were found after ATDs exposure. Administration of P. daemia extract maintained serum biochemical indices as well as antioxidant status similar to control and diminished oxidative stress in dose dependent manner. Histological and ultra-structural observations substantiated biochemical findings. Conclusions: P. daemia has therapeutic potential against ATDs induced liver injury and may be of clinical significance after extensive studies.

Propolis modulates cellular biochemistry, antioxidants, cytokine profile, histological and ultra-morphological status against antituberculosis drugs induced hepatic injury

Objective: To evaluate hepatic injury induced by antituberculosis drugs (ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis (bee hive product) against ATDs induced hepatic injury. Methods: The ATDs were administered for 8 weeks as well as propolis extract at three different doses (100, 200, 400 mg/kg) conjointly for 8 weeks in rats. Silymarin (50 mg/kg) was given as positive control. Animals were euthanized after 8 weeks; blood and liver samples were collected to perform various biochemicals, serological and histopathological and ultramorphological studies. Results: Significant increase (P < 0.05) in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglyceride and cholesterol along with reduction in glucose and albumin level were noted after ATDs induced hepatic injury. Significant increase (P < 0.05) in lipid peroxidation, triglyceride, cholesterol and CYP2E1 activity; decline in reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glucose-6-phosphatase dehydrogenase activity were observed after ATDs intoxication. Due to presence of a wide range of flavonoids and polyphenols in propolis extract, its administration reduced hepatic injury and maintained biochemical indices towards control. Histopathological and electron microscopic observations indicated hepatoprotective potential of propolis at cellular level whereas, TNF-α, IL-6 and IGF-1 confirmed therapeutic potential of propolis at molecular level. Conclusions: It can be concluded that propolis possess hepatoprotective potential against ATDs induced hepatic injury that may prove itself as a clinically useful natural product in management of drug induced liver injury.

Dexmedetomidine attenuates acute alcoholic hepatic injury in mice / 中国病理生理杂志

AIM:To investigate the effects of dexmedetomidine (DEX) on acute alcoholic hepatic injury in mice and to explore the possible mechanisms .METHODS:Kunming mice (n=50) were randomly divided into 5 groups (n=10):normal saline control (NS) group, acute alcoholic hepatic injury model (E) group, low-dose (10μg/kg) DEX (E+L) group, medium-dose (50 μg/kg) DEX (E+M) group and high-dose (100 μg/kg) DEX (E+H) group.The animals were sacrificed at 6 h after gavage of alcohol or normal saline .The levels of alanine aminotransferase ( ALT) , as-partate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH) and superoxide dis-mutase ( SOD) were measured .The livers were removed for evaluation of histological characteristics and determining the content of tumor necrosis factor-α( TNF-α) amd interleukin-1β( IL-1β) in the liver tissues by ELISA .The expression levels of cytochrome P4502E1 (CYP2E1) and nuclear factor -κB (NF-κB) in the liver tissues were evaluated by Western blot.RESULTS:Compared with NS group, the levels of ALT, AST and TG were obviously increased in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the levels of TNF-α, IL-1βand MDA were obviously increase in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the activity of SOD and the content of GSH were obviously decreased in E group , which were obviously increased in E +M and E+H groups.Compared with NS group, the expression of CYP2E1 and NF-κB was obviously increase in E group , which was obviously decreased in E +M and E+H groups.Compared with NS group , ethanol induced marked liver histo- logical injury, which was less pronounced in E +M and E+H groups.CONCLUSION: DEX has a protective effect on mouse liver with acute alcoholic injury by the involvement in the processes of antioxidation and antiinflammation , and its mechanism may be associated with the inhibition of CYP 2E1 and NF-κB expression.