Serum Liver Enzymes Research Articles

Lower muscular strength is associated with greater liver fat content and higher serum liver enzymes-"The Sedentary's Liver" The Study of Health in Pomerania.

We investigated the associations of low handgrip strength (HGS, i.e., a marker of muscular fitness) with liver fat content (LFC) and serum liver enzymes in a population-based setting. We used data from 2700 participants (51.7% women), aged 21-90years, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-START-2 and SHIP-TREND-0). Cross-sectional, multivariable adjusted regression models were performed to examine the associations of HGS with LFC, measured by magnetic resonance imaging and serum liver enzymes. We found significant inverse associations of HGS with both LFC and serum liver enzymes. Specifically, a 10-kg lower HGS was associated with a 0.59% (95% confidence interval [CI]: 0.24-0.94; p=0.001) higher LFC, a 0.051µkatal/L (95% CI: 0.005-0.097; p=0.031) higher gamma-glutamyltransferase (GGT) concentration and a 0.010µkatal/L (95% CI: 0.001-0.020; p=0.023) higher aspartate aminotransferase (AST) concentration. The adjusted odds-ratio for prevalent hepatic steatosis (defined by a MRI-PDFF ≥5.1%) per 10-kg lower HGS was 1.21 (95% CI: 1.04-1.40; p=0.014). When considering only obese individuals, those with low HGS had a 1.58% (95% CI: 0.18-2.98; p=0.027) higher mean LFC and higher chance of prevalent hepatic steatosis (adjusted OR 1.74, 95% CI: 1.15-2.62; p=0.009) compared to individuals with high HGS. We found similar associations in individuals with overweight, but not in those with normal weight. Lower HGS was strongly associated with both higher LFC and higher serum GGT and AST concentrations. Future studies might clarify whether these findings reflect adverse effects of a sedentary lifestyle or aging on the liver.

Subnormal Serum Liver Enzyme Levels: A Review of Pathophysiology and Clinical Significance.

Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson's disease, deficiencies of divalent ions, or malnutrition. Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis, the use of certain medications, and in bone disease. Finally, subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia. The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.

Hepatoprotective perspective of newly synthesized 3-(3,5-bis (tri fluoro methyl) phenyl)- 5-methyl-1-((1-methyl-1h-pyrrol-2-yl) methyl)-2-thioxoimidazolidin-4-one against diethyl nitrosamine induced liver injury in rats with molecular docking investigatio

The hepatoprotective effect of synthesized 3-(3,5-bis (trifluoromethyl) phenyl)-5-methyl-1-((1-methyl-1H-pyrrol-2-yl) methyl)-2-thioxoimidazolidin-4-one (3FL-M) was evaluated against diethyl nitrosamine-induced liver injury (DEN). Wistar rats were divided into 3 groups as: placebo (received 10% tween 80%), hepatotoxic control (injected with 200 mg/kg of DEN) and treatment (injected 200 mg/kg of DEN and received 50 mg/kg oral feeding of the synthesized 3FL-M). Half the number of the rats were sacrificed on 2nd week of the experiment, whereas the other half were sacrificed after 6 weeks. Blood was collected to run liver biochemical analysis, and to evaluate pro-inflammatory cytokines tumor necrosis factor-alpha TNF-α and interleukine6 IL-6. Liver sections were used to detect nuclear protein ki-67 and hepatocyte specific antibody HSA. 3FL-M was subjected to molecular docking calculations based on binding affinities towards TNF-α and IL-6. DEN-treated rats showed elevation in the liver serum enzymes as well as pro-inflammatory cytokines with clear destruction of the hepatic architecture, in contrast 3FL-M treated rats showed normalized liver enzymes and cytokines levels with resolution of the hepatocytes. Molecular modelling revealed that 3FL-M exhibited the significant affinities toward the binding pocket of the TNF-α and IL-6, however, further studies is recommended for developing it as a chemotherapeutic drug-like molecule.
 KEY WORDS: DEN, Hepatoprotective, TNF-α, IL-6, Molecular docking
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 751-763. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.16

Changes in biochemical and sperm parameters of rats drinking energy drinks.

Tiger energy drink is used in this research to see the effect on serum lipid profile, liver enzymes, and kidney function, also observing changes in sperm parameters. Sixteen male rats were divided into four groups, each consisting of four rats. The control group was given water and rat feed, while groups 1, 2, and 3 were given water with Tiger energy drink (25%, 50%, and 75%, respectively) for eight weeks. The results showed that the effect of energy drinks on lipid profile decreased cholesterol, TG, and LDL, while there was a slight increase in HDL. Treatment with wild Tiger energy drink generally caused insignificant increases in GOT and GPT in both G2 and G3 groups as compared to the control. However, in the G1 group, GPT and GOT significantly increased. Accordingly, ALP concentration was significantly increased in all experimental groups compared to the control group. Sperm quality declined as the concentration of energy drinks consumed increased. The potential adverse effects of energy drinks, at their specific dosages, have been determined to include hepatic and renal impairment, as well as alterations in serum lipids. Additional research is required to investigate the specific mechanism by which energy drinks impact spermatogenesis, either through the modulation of endocrine hormones or other metabolic pathways.

Novel thiazolidin-4-one benzenesulfonamide hybrids as PPARγ agonists: Design, synthesis and in vivo anti-diabetic evaluation

In the current study, two series of novel thiazolidin-4-one benzenesulfonamide arylidene hybrids 9a-l and 10a-f were designed, synthesized and tested in vitro for their PPARɣ agonistic activity. The phenethyl thiazolidin-4-one sulphonamide 9l showed the highest PPARɣ activation % by 41.7%. Whereas, the 3-methoxy- and 4-methyl-4-benzyloxy thiazolidin-4-one sulphonamides 9i, and 9k revealed moderate PPARɣ activation % of 31.7, and 32.8%, respectively, in addition, the 3-methoxy-3-benzyloxy thiazolidin-4-one sulphonamide 10d showed PPARɣ activation % of 33.7% compared to pioglitazone. Compounds 9b, 9i, 9k, 9l, and 10d revealed higher selectivity to PPARɣ over the PPARδ, and PPARα isoforms. An immunohistochemical study was performed in HepG-2 cells to confirm the PPARɣ protein expression for the most active compounds. Compounds 9i, 9k, and 10d showed higher PPARɣ expression than that of pioglitazone. Pharmacological studies were also performed to determine the anti-diabetic activity in rats at a dose of 36 mg/kg, and it was revealed that compounds 9i and 10d improved insulin secretion as well as anti-diabetic effects. The 3-methoxy-4-benzyloxy thiazolidin-4-one sulphonamide 9i showed a better anti-diabetic activity than pioglitazone. Moreover, it showed a rise in blood insulin by 4-folds and C-peptide levels by 48.8%, as well as improved insulin sensitivity. Moreover, compound 9i improved diabetic complications as evidenced by decreasing liver serum enzymes, restoration of total protein and kidney functions. Besides, it combated oxidative stress status and exerted anti-hyperlipidemic effect. Compound 9i showed a superior activity by normalizing some parameters and amelioration of pancreatic, hepatic, and renal histopathological alterations caused by STZ-induction of diabetes. Molecular docking studies, molecular dynamic simulations, and protein ligand interaction analysis were also performed for the newly synthesized compounds to investigate their predicted binding pattern and energies in PPARɣ binding site.

Liver enzymes as a predictor of mortality in patients with COVID-19? A cross-sectional study

Liver injury in patients with COVID-19 infection may directly result from viral infection of liver cells, immune-mediated inflammation such as cytokine storm, and hypoxia resulting from pneumonia. Additionally, liver injury may occur due to drug toxicity and may lead to liver failure in critically ill COVID-19 patients. Given the significance of the liver and its vulnerability in COVID-19 patients, this study aimed to investigate the correlation of serum liver enzymes with the prognosis of hospitalized COVID-19 patients at Imam Khomeini Hospital in Urmia. This descriptive-analytical study involved hospitalized COVID-19 patients at Imam Khomeini Hospital in Urmia. Patient data were extracted from medical records and recorded in checklists, including demographic characteristics (age and gender), serum levels of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), and patient outcomes (recovery and mortality). Subsequently, the serum levels of AST and ALT in recovered and discharged patients were compared with those of deceased patients. The mean AST level was higher in deceased patients compared to recovered and discharged patients, and this difference was statistically significant (P <0.033). Therefore, overall, higher AST levels in COVID-19 patients may indicate a worse prognosis. Similarly, the mean ALT level was higher in deceased patients compared to recovered and discharged patients, and this difference was statistically significant (P <0.015). Thus, higher ALT levels in COVID-19 patients may generally indicate a worse prognosis. Continuous monitoring of liver enzymes in patients with a poor prognosis can lead to early identification and, to the extent possible, prevention of complications and mortality through enhanced care.

Treatment of Hypothyroidism with Flavonoid Rich Extract of Fucus vesiculosus L Algae in Adult Rats

Background: Thyroid-related diseases, such as hypothyroidism, affect large populations worldwide and have severe health effects. Fucus vesiculosus L seaweed, which is full of iodine and other biologically active ingredients, has always been recognized as a remedy for hypothyroidism. The objective of this study was to explore the effects of a flavonoid extract of the algae, Fucus vesiculosus L, on the thyroid hormones in rat. Method: Thirty-two mature rats were separated into four categories and given different amounts of the seaweed extract over the span of a month. Blood samples were then taken and assessed for thyroid hormones, antioxidants, and liver enzymes. The effect of the flavonoid extract of the Fucus vesica algae on thyroid hormones in the serum of adult rats was studied, by estimation thyroid hormones, glutathione peroxidase, and peroxynitrite, in addition to liver enzymes in the blood serum of (32) adult rats. Results: The results showed that the TSH level a significant decrease in all groups compared to the control group after a month of dosing. T3 also showed a significant increase in all groups compared to the control, in addition to T4, which showed a significant increase in all groups. As for the level of glutathione peroxidase, it showed a significant decrease in all groups compared to the control group, while peroxynitrite showed a significant decrease in all groups compared to the control group. As for liver enzymes, they showed a significant decrease in all groups compared with the control group. Conclsuion: In summary, the Fucus vesiculosus L. seaweed flavonoid extracts showed a marked deviations in the concentrations of thyroid hormones and exposed potential hepato-protective and antioxidative activity in adult rats.

2,3,5,4′- tetrahydroxystilbene-2-O-β-D- glucopyranoside (TSG)-Driven immune response in the hepatotoxicity of Polygonum multiflorum

Ethnopharmacological relevance2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) as the primary constituent of Polygonum multiflorum Thumb. (PM) possesses anti-oxidative, antihypercholesterolemic, anti-tumor and many more biological activities. The root of PM has been used as a tonic medicine for thousands of years. However, cases of PM-induced liver injury are occasionally reported, and considered to be related to the host immune status. Aim of the studyThe primary toxic elements and specific mechanisms PM causing liver damage are still not thoroughly clear. Our study aimed to investigate the influences of TSG on the immune response in idiosyncratic hepatotoxicity of PM. Materials and methodsThe male C57BL/6 mice were treated with different doses of TSG and the alterations in liver histology, serum liver enzyme levels, proportions of T cells and cytokines secretion were evaluated by hematoxylin and eosin (HE), RNA sequencing, quantitative real time polymerase chain reaction (qRT-PCR), Flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA), respectively. Then, primary spleen cells from drug-naive mice were isolated and cultured with TSG in vitro. T cell subsets proliferation and cytokines secretion after treated with TSG were assessed by CCK8, FCM and ELISA. In addition, mice were pre-treated with anti-CD25 for depleting regulatory T cells (Tregs), and then administered with TSG. Liver functions and immunological alterations were analyzed to evaluate liver injury. ResultsData showed that TSG induced liver damage, and immune cells infiltration in the liver tissues. FCM results showed that TSG could activate CD4+T and CD8+T in the liver. Results further confirmed that TSG notably up-regulated the levels of inflammatory cytokines including TNF-α, IFN-γ, IL-18, perforin and granzyme B in the liver tissues. Furthermore, based on transcriptomics profiles, some immune system-related pathways including leukocyte activation involved in inflammatory response, leukocyte cell-cell adhesion, regulation of interleukin-1 beta production, mononuclear cell migration, antigen processing and presentation were altered in TSG treated mice. CD8+T/CD4+T cells were also stimulated by TSG in vitro. Interestingly, increased proportion of Tregs was observed after TSG treatment in vitro and in vivo. Foxp3 and TGF-β1 mRNA expressions were up-regulated in the liver tissues. Depletion of Tregs moderately enhanced TSG induced the secretion of inflammatory cytokines in serum. ConclusionsOur findings showed that TSG could trigger CD4+T and CD8+T cells proliferation, promote cytokines secretion, which revealed that adaptive immune response associated with the mild liver injury cause by TSG administration. Regulatory T cells (Tregs) mainly sustain immunological tolerance, and in this study, the progression of TSG induced liver injury was limited by Tregs. The results of our investigations allow us to preliminarily understand the mechanisms of PM related idiosyncratic hepatotoxicity.

Hematological profile, inflammatory markers and serum liver enzymes in COVID 19 positive children vs. COVID 19 negative ones-a comparative study.

Complete blood count, C-reactive protein and transaminases are routine laboratory parameters investigated in children with infections, including COVID 19. We aimed to evaluate the diagnostic accuracy of these parameters in children diagnosed with COVID 19. At the time of admission, children with COVID 19 suggestive symptoms were tested RT-PCR for SARS CoV-2 and were allocated to either the study group (RT-PCR SARS CoV-2 positive) or control group (RT-PCR SARS CoV-2 negative). All children were evaluated by complete blood count, CRP, and transaminases. When comparing the two groups, we identified significantly lower values for leukocytes (p < 0.001), neutrophils (p < 0.001), lymphocytes (p < 0.001) and thrombocytes (p = 0.014), but no significantly different values for CRP (p = 0.916) and monocytes (p = 0.082). A diagnostic score for COVID-19 was compiled using the abovementioned parameters-presence of fever, number of lymphocytes and aspartate-aminotransferase. Performance was tested, showing a positive discrimination value (AUC of 0.703)-81.5% sensitivity, 50.6% specificity. The leukocytes, neutrophils and lymphocytes have significantly lower values in COVID-19 children. The proposed score based on the presence of fever the values of lymphocytes and AST has a good sensitivity in predicting COVID-19 infection.

Ipragliflozin and sitagliptin differentially affect lipid and apolipoprotein profiles in type 2 diabetes: the SUCRE study

BackgroundSGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other clinical parameters.MethodsThis is a multicenter, open-label, randomized, controlled trial. Patients with type 2 diabetes (20–74 years old) with HbA1c levels of 7.0-10.5% and serum triglyceride levels of 120–399 mg/dL (1.35–4.50 mmol/L) on diet and/or oral hypoglycemic agents were enrolled. Subjects were randomized to treatment with ipragliflozin (50 mg/day, n = 77) or sitagliptin (50 mg/day, n = 83). Laboratory measurements were performed at 0, 1, 3, and 6 months of treatment.ResultsIpragliflozin and sitagliptin reduced fasting plasma glucose, glycoalbumin, and HbA1c almost equally. Ipragliflozin increased HDL-C and decreased apo E. Sitagliptin decreased TG, apo B48, CII, and CIII, but increased LDL-C. The between-treatment differences were significant for HDL-C (P = 0.02) and apo B48 (P = 0.006), and nearly significant for apo A1 (P = 0.06). In addition, ipragliflozin reduced body weight, blood pressure, serum liver enzymes, uric acid, and leptin, and increased serum ketones compared with sitagliptin.ConclusionsWhile ipragliflozin and sitagliptin showed similar effects on glycemic parameters, the effects on serum lipid and apolipoprotein profiles were different. Ipragliflozin may have an anti-atherogenic effect through modulation of HDL-C and apo E compared to sitagliptin through TG and apo B48, CII, and CIII in patients with type 2 diabetes.

Hepatoprotective Effect of Extra Virgin Olive Oil and Apple Cider Vinegar in Type-2 Diabetic Rat Model

Introduction: Type-2 diabetes mellitus, a major public health problem, is caused by insulin resistance. In diabetics, chronic hyperglycemia results in formation of reactive oxygen species. Oxidative stress in diabetic patients is responsible for hepatic damage because it causes activation of several pro-inflammatory mediators in liver. Hepatic complications of diabetes include fatty liver disease, necrosis, cirrhosis, carcinoma and liver failure. Aims &amp; Objectives: To determine and compare the hepatoprotective effect of extra virgin olive oil and apple cider vinegar in streptozotocin induced Type-2 diabetic rat model. Place and Duration of Study: This experimental study was conducted at Animal House of Postgraduate Medical Institute, Lahore, Pakistan from May 2021 to June 2021. Material &amp; Methods: In this study, 40 male Sprague Dawley rats were divided into 4 groups i.e., Group I was NC (negative control), Group II PC (positive control), Group III EVOO (Extra virgin olive oil) and Group IV (Apple cider vinegar), each group having 10 rats. Diabetes was induced in all rats except the rats of NC group at the start of the study by intraperitoneal administration of injection nicotinamide, followed by injection STZ after 15 minutes. Group III was given 1ml/100gBW/ day EVOO and Group IV was given 2ml/kgBW/day diluted ACV with distilled water in 1:5 orally for 4 weeks. Terminal sampling was performed at the end of the 4th week for estimation of liver enzymes (ALT, ALP and AST) in serum. Data were entered and analyzed in SPSS version 26. p value of ? 0.05 was considered significant. Results: On comparison with PC group, both the treatment groups showed significant decrease in serum ALT levels with p values 0.026 for EVOO and &lt; 0.001 for ACV. Serum ALP levels were also decreased significantly in both the treated groups with p value &lt; 0.001 for EVOO as well as for the ACV group. However, reduction in serum AST levels was nonsignificant with p values 0.082 and 0.058 in EVOO and ACV groups respectively. Conclusion: Both EVOO and ACV have hepatoprotective effect in Type-2 diabetic rats. However, ACV is more effective.

Hepatocellular degeneration in mice co-exposed to in-utero aluminium and cadmium: Implication of a disordered antioxidant and energy homeostatic response in the liver

The current study comprised four groups of pregnant animals viz; Control (CTR) received 10ml/kg of normal saline, Al:10mg/kg of AlCl3, Cd: 1.5mg/Kg of CdCl2 Al+Cd; 10mg/kg of AlCl3 and 1.5mg/Kg of CdCl2. Treatment was done from pregnancy days (PNT) 7-20. After delivery, male animals were weaned on PSD 21 and sacrificed on PSD 78. From the study significant increases on serum liver enzymes in the group exposed to Cd and that exposed to Al+Cd were observed. The study further showed altered serum and hepatic antioxidant balance for the Cd, Al and Al+Cd groups compared to control. Similarly, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activities in the liver were elevated in Cd and Al+Cd groups while an altered liver histological feature in treated groups were also observed. it was concluded that in utero co-exposure to Al and Cd had the ability to alter hepatic functional indices.

Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats.

Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for 4 weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate-cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.

Association of Serum Uric Acid and Liver Enzymes in Adults at Tertiary Level Hospital in Bangladesh

The level of serum uric acid (SUA) has been linked to metabolic syndrome, diabetes, and cardiovascular disease. The purpose of this study was to evaluate the relationship between SUA and serum liver enzymes in a Bangladeshi adult population. This cross-sectional study was conducted among apparently healthy adults aged &gt;18 years, from March 2019 to February 2020 at the Department of Biochemistry, Sir Salimullah Medical College (SSMC), Dhaka. SUA, liver enzymes, lipid profile and other biochemical markers were measured in the collected samples by using standard methods. All statistical analyses were performed by using SPSS version 22.0 software and p&lt;0.05 was considered statistically significant. A total of 140 subjects were selected and blood sample were collected for biochemical analysis. Among them 70 were male and 70 were female. Serum uric acid (SUA), Alanine transaminase (ALT), Aspartate aminotransferase (AST) and Gamma-glutamyl transferase (GGT) levels were significantly (p&lt;0.001) higher in male than female group. Pearson’s correlation analysis showed that there were significant positive correlation between SUA and serum ALT, AST, GGT (p&lt;0.001). However, it also showed significant positive correlation between SUA and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), while negative correlation was found between SUA and high density lipoprotein cholesterol (HDL-C) (p&lt;0.001). The role of SUA in the prediction of elevated liver enzymes showed area under the ROC Curve (AUC) 0.839 for ALT, 0.848 for AST and 0.809 for GGT respectively. SUA is positively related with ALT, AST, GGT in adults. More prospective studies are needed to clarify the complex relationship between SUA and liver enzymes in the general population. Bangladesh Med J. 2022 Sept; 51(3): 18-27

Evening primrose oil enriched with gamma linolenic acid and D/L-alpha tocopherol acetate attenuated carbon tetrachloride-induced hepatic injury model in male rats via TNF-α, IL-1β, and IL-6 pathway

The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4)-induced liver damage model was assessed in this study. Twenty male Albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded. Serum liver enzymes, hepatic malondialdehyde (MDA), hepatic reduced glutathione (GSH) and the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were assessed. The binding affinities of γ-linolenic acid and D/L-alpha tocopherol constituents with IL-1β, IL-6 and TNF-α were investigated using molecular docking simulations. Histopathological and electron microscopic examinations of the liver were performed. The results indicated that CCl4 elevated serum liver enzyme and hepatic MDA levels, whereas GSH levels were diminished. The upregulation of IL-1β, IL-6, and TNF-α gene expressions were induced by CCl4 treatment. The PO/CCl4-treated group showed amelioration of hepatic injury biomarkers and oxidative stress. Restoration of histopathological and ultrastructural alterations while downregulations the gene expressions of TNF-α, IL1-β and IL-6 were observed. In conclusion, evening primrose oil enriched with γ-linolenic acid and D/L-alpha tocopherol acetate elicited a potential amelioration of CCl4-induced hepatic toxicity.

Knocking out Fkbp51 decreases CCl4-induced liver injury through enhancement of mitochondrial function and Parkin activity

Background and aimsPreviously, we found that FK506 binding protein 51 (Fkbp51) knockout (KO) mice resist high fat diet-induced fatty liver and alcohol-induced liver injury. The aim of this research is to identify the mechanism of Fkbp51 in liver injury.MethodsCarbon tetrachloride (CCl4)-induced liver injury was compared between Fkbp51 KO and wild type (WT) mice. Step-wise and in-depth analyses were applied, including liver histology, biochemistry, RNA-Seq, mitochondrial respiration, electron microscopy, and molecular assessments. The selective FKBP51 inhibitor (SAFit2) was tested as a potential treatment to ameliorate liver injury.ResultsFkbp51 knockout mice exhibited protection against liver injury, as evidenced by liver histology, reduced fibrosis-associated markers and lower serum liver enzyme levels. RNA-seq identified differentially expressed genes and involved pathways, such as fibrogenesis, inflammation, mitochondria, and oxidative metabolism pathways and predicted the interaction of FKBP51, Parkin, and HSP90. Cellular studies supported co-localization of Parkin and FKBP51 in the mitochondrial network, and Parkin was shown to be expressed higher in the liver of KO mice at baseline and after liver injury relative to WT. Further functional analysis identified that KO mice exhibited increased ATP production and enhanced mitochondrial respiration. KO mice have increased mitochondrial size, increased autophagy/mitophagy and mitochondrial-derived vesicles (MDV), and reduced reactive oxygen species (ROS) production, which supports enhancement of mitochondrial quality control (MQC). Application of SAFit2, an FKBP51 inhibitor, reduced the effects of CCl4-induced liver injury and was associated with increased Parkin, pAKT, and ATP production.ConclusionsDownregulation of FKBP51 represents a promising therapeutic target for liver disease treatment.Graphical

Cow placenta extract ameliorates d-galactose-induced liver damage by regulating BAX/CASP3 and p53/p21/p16 pathways

Ethnopharmacological relevancePlacenta is a kind of traditional Chinese medicine, known as “Ziheche”, which has the function of tonifying qi and blood, nourishing liver and kidney. Placenta extract (PE) has been used for delaying organismal aging and treating various liver diseases. Cow placenta is a rich natural resource with large mass. Its composition is similar to that of human placenta, but it has not been effectively utilized. However, little is known about the effect of CPE on the liver of aging mice. Aim of the studyThe aim of this study is to explore the protective effect and mechanism of CPE on the liver of d-galactose (D-gal) induced aging mice. Materials and methodsStatistical methods were used to calculate mouse body weight and liver index. Hematoxylin-eosin (H&E) and transmission electron microscopy (TEM) were used to detect the morphological structure of the liver. Automatic biochemical analyzer was used to measure serum biochemical indicators. Three special staining methods were used to observe hepatocytes apoptosis, senescence and proliferation respectively. Relative kits were used to detect oxidative, inflammatory, and aging markers in the liver. Finally, real-time quantitative polymerase chain reaction and western-blot were used to detect aging related signaling pathways. ResultsCPE significantly improved the morphological damage and dysfunction of liver, restored the activities of liver enzymes in serum, and alleviated liver oxidative stress and inflammatory response in D-gal induced aging mice. Furthermore, CPE inhibited hepatocyte apoptosis and senescence, and promoted hepatocyte proliferation by regulating BAX/CASP3 and p53/p21/p16 signaling pathways, ultimately reduced the effects of aging on the liver. ConclusionCPE effectively ameliorated the impact of aging on the liver by inhibiting free radical production or scavenging excessive free radicals, and its mechanism is associated to the regulation of apoptosis and proliferation-related factors.

Comparison of serum uric acid and liver enzyme levels in adolescents with obesity and with metabolic syndrome

a relationship has been observed between elevated levels of liver enzymes and uric acid with the presence of metabolic syndrome (MS) in the pediatric population. to compare serum liver enzyme and uric acid levels between adolescents with and without MS. a cross-sectional study was carried out in adolescents with obesity between 10 and 18 years old. Somatometric data, serum insulin, lipid profile, uric acid levels and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyl transferase [GGT]) were analyzed. Student's t test or the Chi-square test was used to evaluate differences between groups. a total of 1095 adolescents with obesity were included (444 with MS and 651 without MS). The group with MS had a higher BMI (with MS 2.28 vs without MS 2.11 p < 0.001), with no difference in body fat (42.9 % vs 42.9 %, p = 0.978). The MS group had significantly higher levels of AST (34.4 vs. 29.5, p = 0.013), ALT (42.2 vs. 34.6, p = 0.003), and uric acid (6.17 vs. 5.74, p = 0.002). comparison to the group without MS. The proportion of ALT (40.5 % vs 29.5 %, p = 0.029) and altered uric acid (58.1 % vs. 45.6 %, p = 0.019) was higher in the MS group. serum levels of ALT, AST and uric acid in adolescents with obesity and MS were higher compared to those without MS. Altered ALT was a risk factor for SM.

Ameliorative effects of umbelliferone against acetaminophen-induced hepatic oxidative stress and inflammation in mice.

Acetaminophen (APAP) is a commonly used antipyretic and pain reliever that its overdose causes acute liver toxicity. Umbelliferone (UMB) has many pharmacological effects. In this study, the hepatoprotective effect of UMB on acute hepatotoxicity induced by APAP was investigated. Forty-nine male mice were separated into seven groups. The control received vehicle (i.p.), UMB group received UMB (120 mg/kg, i.p.), APAP group was treated with a single dose of APAP (350 mg/kg, i.p.), and pretreated groups received N-acetylcysteine (NAC, 200 mg/kg, i.p.) or different doses of UMB (30, 60, and 120 mg/kg, i.p.), respectively before APAP. Twenty-four hours after APAP injection, mice were sacrificed and blood and liver samples were collected. Then, serum and tissue samples were investigated for biochemical and histological studies. A single dose of APAP caused elevation in the serum liver enzymes, including alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. The amounts of thiobarbituric acid reactive substances, tumor necrosis factor-alpha, and nitric oxide increased in the mice's liver tissue. Moreover, the amount of total thiol and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) significantly diminished in the APAP group. Histological results confirmed the hepatotoxicity induced by APAP. However, UMB (more effective at 60 and 120 mg/kg) lessened APAP-induced hepatic injuries, which is comparable with NAC effects. The findings of this study provided evidence that UMB ameliorates liver injury induced by APAP through its antioxidant and anti-inflammatory effects.

Serum Gamma Glutamyltransferase: A Biomarker for Identifying Postprandial Hypertriglyceridemia.

Elevated serum gamma-glutamyltranspeptidase (GGT) is an independent marker of the activation of systemic inflammation, while conditions associated with elevated triglyceride (TG) levels, such as type 2 diabetes, non-alcoholic fatty liver disease, obesity, and metabolic syndrome, are associated with an increased inflammatory burden. Moreover, serum liver enzymes (GGT, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are associated with metabolic syndrome and its components, including hypertriglyceridemia. However, the relationship between liver enzymes and postprandial hypertriglyceridemia (PHTG) remains unclear. Therefore, in this study we conducted oral fat tolerance tests (OFTTs) to understand the differences in serum liver enzyme levels among individuals with different lipid tolerance levels and their correlation with PHTG. For the OFTT, we enrolled 202 non-diabetic volunteers whose fasting triglyceride (TG) levels were less than 1.7 mmol/L in this case-control study. The participants were categorized into two groups according to the TG levels at the 0- and 4-h OFTT: a postprandial normal TG (PNTG) group and a PHTG group. Routine fasting serum biochemical indices, liver enzyme (GGT, ALT, AST, and ALP) levels, and 0- and 4-h OFTT lipid levels were assessed. The PHTG group had significantly higher serum GGT and ALT levels and a lower AST/ALT ratio than those in the PNTG group. However, no significant difference was observed in AST and ALP levels compared with the PNTG group. After adjusting for major confounders, logistic regression analysis indicated a significant correlation between serum GGT and PHTG (odds ratio = 1.168, P < 0.001), but not with ALT level, AST level, AST/ALT ratio, and ALP level. The receiver operating characteristic curve analysis demonstrated that the serum GGT level was an effective predictor of PHTG. Serum GGT levels are significantly associated with PHTG risk and serve as an effective biomarker for early identification.