Serum Aspartate Aminotransferase Research Articles

Mechanism of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata herbal pair in promoting hepatocellular regeneration in chronic acute liver failure based on HGF/PI3K/Akt signaling axis

Based on the hepatocyte growth factor(HGF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling axis, this study investigated the therapeutic effect of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata(PRR-ALRP) her-bal pair on acute-on-chronic liver failure(ACLF) rats and its impact on hepatocellular regeneration. The rat model of ACLF was constructed by subcutaneous and tail vein injection of bovine serum albumin combined with intraperitoneal injection of lipopolysaccharides(LPS)+D-galactosamine(D-GalN). The rats were divided into normal control(NC) group, model(vehicle) group, PRR-ALRP(5.85 g·kg~(-1)) group, and hepatocyte growth factor granules(HGFG, 4.05 g·kg~(-1)) group. Hematoxylin-eosin(HE) staining was used to observe pathological changes in rat liver tissues. Serum alanine aminotransferase(ALT), aspartate transaminase(AST), and total bilirubin(TBIL) were detected using an automatic biochemical analyzer. The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) inflammatory factors were detected by ELISA. Immunofluorescence staining was used to detect the positive expression of proliferating cell nuclear antigen(PCNA), antigen identified by monoclonal antibody(Ki67), and cell cycle protein B1(CyclinB1). Real-time fluorescence-based quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of HGF, growth factor receptor-bound protein 1(Gab1), PI3K, Akt, phosphorylated PI3K(p-PI3K), and phosphorylated Akt(p-Akt). The results showed that compared with the vehicle group, the PRR-ALRP group had reduced liver tissue pathological scores, improved liver function, and reduced inflammatory response, with enhanced PCNA, Ki67, and CyclinB1 fluorescence expression. Furthermore, compared with the model group, the PRR-ALRP group showed upregulated expression of HGF and Gab1 proteins, as well as activation of PI3K and Akt phosphorylation. These findings suggest that PRR-ALRP herbal pair exerts anti-liver failure effects by alleviating hepatocyte inflammatory damage and promoting hepatocellular regeneration, and its specific regulatory mechanism may be related to the activation of the HGF/PI3K/Akt signaling pathway.

SEA Alleviates Hepatic Ischaemia-Reperfusion Injury by Promoting M2 Macrophage Polarisation.

Hepatic ischaemia-reperfusion (I/R) injury is a frequent and nearly inevitable pathophysiological process without widely accepted effective therapy. Soluble egg antigen (SEA) of Schistosoma japonicum (S. japonicum) is the main mediators capable of regulating immunological activities and has received increased attention in immune-mediated diseases. But its role in hepatic I/R injury has not been well defined. This study aimed to elucidate whether SEA protects liver against hepatic I/R injury and explore underlying mechanism. After intraperitoneal injecting SEA three times a week for 4 weeks, mice underwent 70% hepatic I/R injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), haematoxylin-eosin (HE) and TdT-mediated dUTP nick-end labelling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response was also investigated. Furthermore, immunofluorescence was used to detect macrophage polarisation. Compared with the hepatic I/R injury group, SEA pretreatment significantly alleviated hepatic I/R injury induced liver damage, apoptosis and inflammatory. Interestingly, SEA enhanced the polarisation of macrophages towards M2 macrophages in vivo. We are the first to investigate the therapeutic efficacy of S. japonicum SEA in a hepatic I/R injury model in mice. We provided the first direct evidence that SEA attenuated hepatic I/R injury by promoting M2 macrophage polarisation.

Evaluation of the chemical constituents and toxicological potentials of <i>Asystasia vogeliana benth</i>. leaf extract

Majority of the tradomedicinal uses of Asystasia vogeliana lack scientific backing. Therefore, this study sought to investigate the phytochemical constituents and the toxicological potentials of methanolic leaf extract of Asystasia vogeliana in Swiss albino mice. Air-dried pulverized leaves (1248 g) of Asystasia vogeliana were extracted with methanol for 48 h. The extract was concentrated using rotary evaporator to obtain crude methanol extract (99.8 g). The extract was screened for phytochemicalconstituents and partitioned with n-exane and dichloromethane (DCM). The two fractions were subjected to GC-MS analysis. Acute toxicity study was conducted in Swiss albino mice based on standard procedures. Biochemical parameters were determined in the liver, kidney and blood of the animals. Flavonoids, steroids, saponins and triterpenes were detected in the extract. GC-MS analysis of the n-hexane fraction showed presence of n-hexadecanioc acid (24.01%) and 6-octadecenioc acid (36.68%) as major constituents while oxypurinol (15.68%), and 2,2- dimethylcyclohexan-1,3- dione dioxime (11.21%) were the main constituents in dichloromethane fraction. No mortality was recorded in the acute toxicity study. Liver and blood serum aspartate transaminase (AST) and alanine transaminase (ALT) activities increased across the group. The creatinine and urea content in the kidney and blood serum increased. The insignificant increase in creatinine and urea levels in the kidney and blood showed mild toxicity. Also, increase in AST and ALT level was noticed in the blood which showed liver injury. Therefore, the study concluded that the extract at the tested concentration is mildly nephrotoxic and hepatotoxic.

Replacing soybean meal with fermented rapeseed meal in diets: potential effects on growth performance, antioxidant capacity, and liver and intestinal health of juvenile tilapia (Oreochromis niloticus).

This study aims to evaluate the effects of substituting soybean meal with fermented rapeseed meal (FRM) on growth, antioxidant capacity, and liver and intestinal health of the genetically improved farmed tilapia (GIFT, Oreochromis niloticus). A total of 450 tilapia (7.22 ± 0.15g) were fed with five experimental diets, including a basal diet containing 40% soybean meal (CP0), which was subsequently replaced by 25% (CP25), 50% (CP50), 75% (CP75), and 100% (CP100) FRM in a recirculated aquiculture system for 9weeks (30 fish per tank in triplicates). The results showed that the weight gain, specific growth rate, feed intake, feed efficiency, hepatosomatic index, and viscerosomatic index of fish in both CP75 and CP100 groups were significantly lower than those in CP0 group (P < 0.05). The fish in CP100 group had the lower content of muscle crude protein while the higher level of muscle crude lipid (P < 0.05). Activities of serum aspartate aminotransferase, alanine aminotransferase along with total triglyceride in CP100 group were significantly higher than those in CP0 group (P < 0.05). There were no significant differences in the contents of liver protease, amylase, and lipase among five groups (P > 0.05). The activities of liver total antioxidant capacity and superoxide dismutase exhibited the increased tendency with the increase of FRM replacement levels from 25 to 50% (P < 0.05), while then significantly decreased from 75 to 100% (P < 0.05). Histological morphology indicated that the fish in between CP75 and CP100 groups had poor liver and intestine health. Intestinal microbial diversity analysis showed that the relative abundance of Cetobacterium and Alcaligenaceae in both CP75 and CP100 groups were lower than that in other three groups. In conclusion, the maximum replacement level of soybean meal with FRM in the diet was determined to be 50% without compromising the growth performance, antioxidant status, and liver and intestinal health of tilapia under the current experimental conditions. The observed decrease in food intake and subsequent retarded growth performance in the CP75 and CP100 groups can be attributed directly to a reduction in feed palatability caused by FRM.

Astaxanthin ameliorated isoproterenol induced myocardial infarction via improving the mitochondrial function and antioxidant activity in rats.

The present study evaluated the cardioprotective effect of astaxanthin (ASX) against isoproterenol (ISO) induced myocardial infarction in rats via the pathway of mitochondrial biogenesis as the possible molecular target of astaxanthin. The control group was injected with normal physiological saline subcutaneously for 2 days. The second group was injected with ISO at a dose of 85 mg/kg bwt subcutaneously for 2 days. The third, fourth and fifth groups were supplemented with ASX at doses of 10, 20, 30 mg/kg bwt, respectively daily by oral gavage for 21 days then injected with ISO dose of 85 mg/kg bwt subcutaneously for 2 successive days. Isoproterenol administration in rats elevated the activities of Creatine kinase-MB (CK-MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and other serum cardiac biomarkers Troponin-I activities, oxidative stress biomarkers, malondialdehyde(MDA), Nuclear factor-kappa B (NF-KB), while it decreased Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), Nuclear factor erythroid-2-related factor 2 (Nfe212), mitochondrial transcriptional factor A (mt TFA), mitochondrial DNA copy number and glutathione system parameters. However, Astaxanthin decreased the activities of serum AST, LDH, CK-MB, and Troponin I that elevated by ISO. In addition, it increased glutathione peroxidase and reductase activities, total glutathione and reduced GSH content, and GSH/GSSG ratio, mtDNA copy number, PGC-1α expression and Tfam expression that improved mitochondrial biogenesis while it decreased GSSG and MDA contents and NF-KB level in the cardiac tissues. This study indicated that astaxanthin relieved isoproterenol induced myocardial infarction via scavenging free radicals and reducing oxidative damage and apoptosis in cardiac tissue.

Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus.

Radioactive iodine-125 (125I) microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors, especially hepatocellular carcinoma. Patients with hepatocellular carcinoma frequently experience portal vein embolism, which exacerbates the difficulty and complexity of treatment. 125I particles, used in local radiotherapy, can directly act on tumor tissue and reduce damage to surrounding healthy tissue. Through retrospective analysis, this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment. To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function. The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed. Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein (combination group), while 44 patients received treatment with transcatheter arterial chemoembolization alone (control group). The therapeutic effects on tumor lesions, primary liver cancer, and portal vein tumor embolisms were compared between the two groups. Changes in relevant laboratory indexes before and after treatment were evaluated. The t test was used to compare the measurement data between the two groups, and the χ 2 test was used to compare the counting data between groups. The tumor lesion response rate in the combination group (59.62% vs 38.64%) and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus (80.77% vs 59.09%) were significantly greater than those in the control group (χ 2 = 4.196, 5.421; P = 0.041, 0.020). At 8 wk after surgery, the serum alpha-fetoprotein, portal vein main diameter, and platelet of the combined group were significantly lower than those of the control group, and the serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were significantly greater than those of the control group (t = 3.891, 3.291, 2.330, 3.729, 3.582, 4.126; P < 0.05). The serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery (P < 0.05), and the peripheral blood platelet, alpha-fetoprotein, and main portal vein diameter were significantly less than those of the same group before surgery (P < 0.05). In patients with primary liver cancer and a thrombus in the portal vein, transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone. However, during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.

The role of C5aR1-mediated hepatic macrophage efferocytosis in NASH

Non-alcoholic fatty liver disease (NAFLD) has become the first major chronic liver disease in developed countries. 10–20% of NAFLD patients will progress to non-alcoholic steatohepatitis (NASH), and up to 25% of NASH patients may develop cirrhosis within 10 years. Therefore, it is critical to find key targets that may treat this disease. Here, we identified C5aR1 as a highly-expressed gene in NASH mouse model through analyzing Gene Expression Omnibus (GEO) database and confirmed its higher expression in livers of NASH patients than that of NAFL patients. Meanwhile, we verified its positive correlation with patients’ serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In vivo and in vitro experiments revealed that knocking down C5aR1 in liver significantly reduced liver weight ratio and serum ALT and AST levels and attenuated inflammatory cell infiltration and cell apoptosis in the liver of NASH mice as well as enhanced the efferocytotic ability of liver macrophages, suggesting that C5aR1 may play a crucial role in the efferocytosis of liver macrophages. Furthermore, we also found that the expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and other inflammation-related factors in the liver were significantly reduced. Our work demonstrates a potential mechanism of how C5aR1 deficiency protects against diet-induced NASH by coordinating the regulation of inflammatory factors and affecting hepatic macrophage efferocytosis.

Probiotic Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 improved liver function and uric acid management-A pilot study.

Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023.

Magnitude of change in prepartum feed intake: Estimations using multiple classes of predictors and associations with transition metabolism, health, and milk production

The objectives of this study were to identify factors associated with the relative change in prepartum DMI (RCDMI) of 273 cows fed individually, evaluate the performance of linear models to estimate RCDMI using different classes of predictors, and characterize the implications of RCDMI to transition metabolism, health, and subsequent milk production. Two periods of interest were established. Period 1 comprised d -21 to -12 relative to calving, when DMI was stable. Period 2 comprised d -4 to -1, when average DMI was distinctly declined. The RCDMI from period 1 to 2 was calculated as a percentage value, which ranged from -75% to 15% and averaged -18.1% (± 15.0%). Season, parity, body fatness, body weight, milk production in the previous lactation and at dry-off, and length of dry period were associated with RCDMI and explained 11% of the variation in all cows, and 19% when only parous cows were considered. Performance of linear models to predict RCDMI was improved when data on rumination and physical activities and target blood metabolites were added. The adjusted R2 increased to values between 0.45 and 0.55, and selected models performed consistently in cross-validation analyses. To evaluate the implications of RCDMI, cows were ranked within parity according to RCDMI and classified into terciles as large decline (LDec), moderate decline (MDec), or small decline (SDec). By design, DMI did not differ between tercile groups in period 1 (13.3 ± 0.2 kg/d), but differed substantially in period 2 (LDec = 8.8; MDec = 11.2; SDec = 12.7 ± 0.2 kg/d), creating important differences in RCDMI among groups (LDec = -33.8; MDec = -16.2; SDec = -3.4% ± 0.8%). At enrollment, cows in the LDec and MDec groups were heavier (LDec = 788; MDec = 775; SDec = 750 ± 7 kg), and the proportion of cows with BCS >3.5 was higher in LDec (LDec = 63%; MDec = 47%; SDec = 38%). An interaction between group and time was observed for postpartum DMI, which started lower in LDec than in SDec cows, equaled by the end of transition, and inverted at wk 13 and 14 after calving. Yields of ECM were greater in LDec than in SDec cows, and both groups did not differ from MDec (LDec = 41.0; MDec = 40.3; SDec = 39.0 ± 0.5 kg/d). The LDec cows had decreased energy balance and greater concentrations of nonesterified fatty acids, β-hydroxybutyrate, and aspartate aminotransferase in serum, and greater glutathione peroxidase activity in plasma than SDec cows. Larger declines in prepartum DMI were also associated with increased risk for postpartum disease, although the associations were only weak to moderate. In conclusion, a large decline in prepartum DMI of cows fed ad libitum was associated with important adjustments in the energy metabolism and antioxidants activities, and greater milk production in the subsequent lactation. These findings indicate that feed intake decline close to parturition is likely a normal response to physiological adaptations at the onset of lactation when cows are fed ad libitum.

Effect of arginine, glycine + serine concentrations, and guanidinoacetic acid supplementation in vegetable-based diets for chickens

The study investigated guanidinoacetic acid (GAA) supplementation with varying dietary digestible arginine (Arg) and glycine+serine (Gly+Ser) concentrations in the starter phase, exploring respective carry-over effects on growth performance, blood chemistry, incidence of pectoral myopathies and proximate composition in broilers. A total of 2,800 one-day-old male broiler chicks were distributed in a central composite design with 2 factors and double experimental mesh, represented by supplementation or omission of 0.6 g per kg of GAA, with a central point represented by 107% of Arg and 147% of Gly+Ser, 4 factorial points (combinations of Arg/Gly+Ser concentrations: 96.4/132.5%; 117.6/132.5%; 96.4/161.5%, and 117.6/132.5%), and 4 axial points (combinations of axial points estimated for Arg and Gly+Ser, with the central points of 92/147%; 122/147%; 107/126.5, and 107/167.5%), totaling 18 treatments, 4 repetitions to factorial and axial points, 24 replicates to the central point, and 25 birds per pen. Feed conversion ratio (FCR) from d 1 to 10 had a linear response (P = 0.009) for the decreasing Arg content and a quadratic response (P = 0.047) for Gly+Ser concentrations. Broilers supplemented GAA had lower FCR compared with nonsupplemented groups from d 1 to 10 (P = 0.048) and d 1 to 42 (P = 0.026). Aspartate aminotransferase (AST) exhibited increasing and decreasing linear effects as a function of Arg (P = 0.008) and Gly+Ser (P = 0.020) concentrations, respectively. Guanidinoacetic acid decreased serum AST (P = 0.028). Guanidinoacetic acid reduced moderate + severe (P = 0.039) and mild (P = 0.015) Wooden Breast scores. The occurrence of normal White Striping increased (P = 0.002), while severe score was reduced (P = 0.029) with GAA supplementation. In conclusion, increased digestible Arg:Lys and 14% and 6% above the recommendations (107% and 147%), respectively, provided improved FCR during the starter phase. Dietary GAA supplementation (0.6 g per kg) improved FCR, reduced severity of breast myopathies and appears to have reduced muscle damage in broilers fed plant-based diets.

Potential role of two-dimensional shear wave elastography, including liver stiffness measurement and dispersion slope, for management of chronic hepatitis B.

This study assessed the use of liver stiffness (LS) and dispersion slope (DS) in classifying patients with chronic hepatitis B (CHB) by the necessity of antiviral treatment. A retrospective review examined 249 patients with CHB (male:female, 107:142; mean age, 53±14 years) between April 2018 and March 2022. Patients for whom treatment was indicated, termed group 1, exhibited either serum alanine transaminase (ALT) and aspartate aminotransferase levels not exceeding five times the upper limit of normal and LS &gt;13 kPa, or hepatitis B virus DNA &gt;2,000 IU/mL and ALT &gt;40 IU/L. The remaining patients comprised group 2 (treatment not required). In subgroup analysis, patients with LS &lt;13 kPa were further examined. Overall, group 1 exhibited significantly higher LS (12.64±6.76 vs. 6.31±1.67 kPa, P&lt;0.001) and DS (15.52±4.95 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001) than group 2. In subgroup analysis, group 1 also demonstrated significantly higher values (LS: 8.05±2.12 vs 6.31±1.67 kPa, P&lt;0.001, DS: 13.06±2.75 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001). The areas under the curve (AUCs) for LS and DS in group 1 were 0.855 (95% confidence interval [CI], 0.80 to 0.90; P&lt;0.001) and 0.810 (95% CI, 0.75 to 0.86; P&lt;0.001), respectively. In subgroup analysis, the AUCs for LS and DS in group 1 were 0.751 (95% CI, 0.69 to 0.81; P&lt;0.001) and 0.711 (95% CI, 0.64 to 0.77; P&lt;0.001), respectively. Within group 1, the AUCs for LS and DS did not differ significantly (P&gt;0.05). LS and DS assist in classifying patients with CHB by their need for antiviral treatment.

Hepatotoxic Effects of an Oral Amiodarone in White Albino Rats: Sub-Acute Biochemical, and Histopathological Assessments

Amiodarone, potent antidysrhythmic, widely used drug that has been associated with hepatic toxicity in long-term or excessive use. In the presented study twelve rats were allocated into two groups and given daily doses via gastric gavage orally for two weeks as follows; The first group served as a control normal group, whereas the second got amiodarone at a dosage of 300mg/kg/day orally. Liver tissues were processed for light microscopy, and blood samples were examined for serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and phospholipase a2 enzyme (Pla2) (which are thought to be an indicator of phospholipidosis and lipid buildup). Amiodarone was shown to produce hepatic histological abnormalities such as blood vessel congestion, leucocytic infiltration, liver degeneration, and stages of steatosis and necrosis of hepatocytes. The biochemical assessments were revealed that there was an elevation in amiodarone group's ALT and AST levels as a result of hepatic necrosis leading to leakage of enzymes content, while serum Pla2 was lowered significantly. Also, histopathology indicates stages of steatosis (Lipid accumulation) in hepatocytes, which may lead to farther damage in the late stages of hepatotoxicity.

Association of Ultrasound Abdomen Findings with Liver Function Test and Alcohol Use Disorders Identification Test Scores in Cases of Alcohol Use Disorder

Introduction: There are three independent variables used in clinical practice to evaluate patients suffering from alcohol use disorder (AUD); these are Alcohol Use Disorders Identification Test (AUDIT), liver function tests (LFTs), and imaging findings on ultrasound of the abdomen. There is limited literature about the association of imaging findings with LFT and AUDIT scores in cases of AUD. Objective: The study was conducted to determine the association of ultrasound abdomen findings with LFTs and AUDIT scores in patients with AUD. Methods: This study was conducted using data from 439 patients of AUD (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) treated in the psychiatry department of a tertiary care hospital. The data hence obtained were subjected to statistical analysis. The ordinal data sets were compared using the Chi-square test, and P &lt; 0.05 was taken as statistically significant. Results: The ultrasonography (USG) findings of hepatic/portal system changes in patients of AUD show a significant association with the corresponding changes in AUDIT scores, serum bilirubin, and aspartate transaminase (AST) levels. The ultrasound findings were also significantly associated with total years of drinking and average drinking (in g) per day in the last 3 years. The USG findings did not show a significant statistical association between ALT (alanine transaminase) and serum gamma-glutamyl transferase levels. Conclusion: In patients with alcohol use disorder, USG abdomen findings correlate with the severity of dependence as indicated by years of drinking, average alcohol consumption per day for the last 3 years, AUDIT score (last 1 year), and markers of liver injury (serum bilirubin and AST). Combined use of clinical severity indicators (e.g., AUDIT), lab parameters, and USG abdomen can help in the early diagnosis of ALD.

The Hepatoprotective Effect of Glycyrrhiza glabra Roots Extract Against Amiodarone Induced Hepatotoxicity in Male Rats

Amiodarone (AMD), a powerful antidysrhythmic medication, can cause hepatotoxicity when used long-term or in high doses. It affects both mitochondrial and lysosomal function because of its lipophilic nature and accumulation in tissues. It also has direct production of ROS. Glycyrrhiza glabra is one of the medicinal plants that have been commonly used for thousands of years. It possesses anti-ulcer, anti-inflammatory and antioxidant properties. In this study, the antihepatotoxic effect of Gg was evaluated against AMD liver toxicity in rats model, thirty rats were taken and divided evenly into five groups given daily doses by gastric gavage oral tube for 3 weeks as follows: the 1st group acted as a control group given D.W., and the 2nd group received AMD at a dose of 300mg/kg for 2 weeks. 3rd, 4th, and 5th groups were pretreated with Gg in doses of 200, 400, and 800 mg, respectively, for one week, then along with AMD for 2 weeks. Hepatic damage, revealed by histology and the increased activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum phospholipase A2 (PLA2) was decreased in the AMD group. Gg extract significantly reduced the elevated AST and ALT levels caused by AMD intoxication, rendering PLA2 to its normal level. It also enhanced liver superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels. Gg extract markedly reverses the increased serum TNF levels induced by AMD; therefore, it may be considered a good hepatoprotective agent.

The Possible Protective Role of Resveratrol against Zinc Oxide Nanoparticles Induced Hepatic Tissue Injury in Adult Albino Rat

Abstract Background Zinc oxide nanoparticles (ZnO NPs) are widely used in industries and medications. This may elevate the probability of their existence in the environment, which may have harmful side effects on different body organs, especially on the liver. So it became mandatory to search for natural hepatoprotective elements such as Resveratrol. Aim of the Work The aim of the present work was to determine the effect of zinc oxide nanoparticles on the histological structure and biochemical markers of the liver of adult male albino rats and to evaluate the possible protective role of Resveratrol. Material and Methods 40 adult male albino rats aged 3-6 months, were divided randomly into four groups; Group I (Control group), which consisted of 10 male albino rats with free access to food (rat chew) and water; Group II (ZnO NPs group), which included 10 male albino rats, which received a dose of 50 mg/kg body weight ZnO NPs through oral gavage daily for 4 weeks; Group III (Resveratrol group) was composed of 10 male albino rats which received a dose of 20 mg/kg body weight Resveratrol through oral gavage daily for 4 weeks, and Group IV (ZnO NPs + Resveratrol group) included 10 male albino rats which were co-administered with a combination of ZnO NPs at a dose of 50mg/kg body weight and Resveratrol at a dose of 20 mg/kg body weight dose through oral gavage daily for 4 weeks. At the end of the experiment, blood samples were collected for serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). All the animals were sacrificed, and the liver was extracted and processed into paraffin blocks for light microscopic examination. A morphometric study and a statistical analysis were done. Results The present work demonstrated that liver sections obtained from adult male albino rats that received ZnO NPs showed disorganized hepatic architecture, severe affection of the hepatocytes, which had small darkly stained nuclei, and deep acidophilic cytoplasm. The hepatocytes sometimes showed extensive cytoplasmic vacuolations. Most hepatocytes had small apoptotic nuclei and were surrounded by clear halos. While some hepatocytes lost their cell boundaries and coalesced together. Central veins were dilated, distorted, and congested with areas of epithelial lining detachment. Most of the blood sinusoids appeared congested with marked inflammatory cell infiltration. The portal tracts showed vascular congestion, dilatation, and proliferation of the bile ducts. There was a marked increase in the collagen deposition around the portal tracts, central veins, and in-between hepatocytes. Marked depletion of glycogen content with sporadic positive PAS reactions within the cytoplasm of the hepatocytes was also noticed. Hepatocyte apoptosis was evident by a significant increase in caspase-3 expression compared to the control group. On the other hand, ZnO NP +Resveratrol group showed the restoration of normal hepatic lobules with few areas of subcapsular haemorrhage. Most hepatocytes appeared polygonal in shape, with acidophilic cytoplasm and central rounded vesicular nuclei. While few hepatocytes appeared degenerated with dark stained pyknotic nuclei and cytoplasm showed hydropic degeneration. Most of the blood sinusoids returned to their normal sizes with flattened endothelial cells. However, sometimes they were congested, dilated, and contained Kupffer cells. Some central veins appeared congested. The portal tract also returned to its normal size with a marked decrease in inflammatory cell infiltration and showed apparent minimal collagen fiber deposition. Another finding in the present work was that Resveratrol restored the glycogen content of the hepatocytes which were depleted in ZnO NPs group. This was marked by a strong PAS positive reaction in the cytoplasm of most hepatocytes, with few hepatocytes with weak PAS reaction. Resveratrol co-treatment with ZnO NPs significantly reduced the degeneration and necrosis of hepatocytes. This was evident in our study by the apparent negative Caspase-3 reaction in the cytoplasm of most hepatocytes. Clear deterioration of liver function tests was observed in ZnO NPs group compared with the control, with marked improvement in the group treated with ZnO NPs and Resveratrol together. Conclusion The present study demonstrated the degenerative and hepatotoxic effects of ZnO NPs on the histological structure and function of the liver and the hepatoprotective role of Resveratrol against these effects.

The cytochrome P4501A1 (CYP1A1) inhibitor bergamottin enhances host tolerance to multidrug-resistant Vibrio vulnificus infection

PurposeVibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. MethodsAn increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. ResultsIn mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637). ConclusionBergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Effect of Orchidectomy on Hepatic Ischemia/Reperfusion Injury

Abstract Background Little attention has been paid to investigate the effect of orchidectomy on hepatic ischemia/reperfusion (I/R) injury, which is lacking. The Aim of This Study is to evaluate the possible impact of orchidectomy and/or testosterone treatment on the function and structure of liver in rat model of hepatic I/R injury and, also, to explore the possible underlying mechanism(s). Materials and Methods 65 male Wistar albino-rats were divided into 5 groups; sham- operated control group (Sham), hepatic ischemia/reperfusion group (hepatic I/R), orchidectomized hepatic ischemia/reperfusion group (Orch+I/R), Testosterone- treated hepatic ischemia/reperfusion group (T+I/R) and Orchidectomized testosterone-treated hepatic ischemia/reperfusion group (Orch+T+I/R). All rats were subjected to determination of serum levels of alanine transaminase (ALT), aspartate transaminase (AST), testosterone and estradiol, and hepatic tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor- alpha (TNF-α) and gene expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Also, hepatic tissues were histopathologically assessed. Results Hepatic I/R was associated with significant rise of serum ALT and AST, and hepatic tissue TNF-α, NF-κB and MDA, and significant reduction of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2. Histopathological analysis showed vacuolization of the cytoplasm, dilated sinusoids, inflammatory cells infiltration, increased collagen fibers and significantly increased caspase-3. Hepatic I/R -mediated effects were aggravated following orchidectomy, however preischemic treatment with testosterone protected the liver as shown by the significant decline in ALT and AST, and hepatic tissue MDA, TNF-α and NF-κB, and significant enhancement of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2, and restoration of hepatic architecture. Conclusion Orchidectomy hypersensitizes the liver to ischemic injury, due to exaggeration of oxidative and inflammatory states and apoptosis, while testosterone treatment improved the hepatic I/R detrimental effects on liver function and morphology due to its suppressive effect on oxidative and inflammatory states and apoptosis.

Splice-switching antisense oligonucleotide controlling tumor suppressor REST is a novel therapeutic medicine for neuroendocrine cancer

RNA splicing regulation has revolutionized the treatment of challenging diseases. Neuroendocrine cancers, including small cell lung cancer (SCLC) and neuroendocrine prostate cancer (PCa), are highly aggressive, with metastatic neuroendocrine phenotypes, leading to poor patient outcomes. We investigated amido-bridged nucleic acid (AmNA)-based splice-switching oligonucleotides (SSOs) targeting RE1-silencing transcription factor (REST) splicing as a novel therapy. We designed AmNA-based SSOs to alter REST splicing. Tumor xenografts were generated by subcutaneously implanting SCLC or PCa cells into mice. SSOs or saline were intraperitoneally administered and tumor growth was monitored. Blood samples were collected from mice after SSO administration, and serum alanine aminotransferase and aspartate aminotransferase levels were measured to assess hepatotoxicity using a biochemical analyser.Invitro, REST_SSO reduced cancer cell viability. In a tumor xenograft model, it exhibited significant antitumor effects. It repressed REST-controlled RE1-harboring genes and upregulated miR-4516, an SCLC biomarker. Our findings suggest that REST_SSO suppresses tumorigenesis in neuroendocrine cancers by restoring REST function. This novel therapeutic approach holds promise for intractable neuroendocrine cancers such as SCLC and neuroendocrine PCa.

Navigating Disease Management: A Comprehensive Review of the De Ritis Ratio in Clinical Medicine.

The De Ritis ratio, defined as the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, is a widely recognized biochemical marker with significant applications in diagnosing and managing various diseases, particularly liver disorders. This comprehensive review synthesizes current knowledge surrounding the clinical relevance of the De Ritis ratio, examining its historical development, diagnostic utility, and prognostic significance across various medical conditions, including liver diseases, cardiovascular disorders, and muscular pathologies. Through an in-depth analysis of literature spanning several decades, this review highlights the role of the De Ritis ratio not only in differential diagnosis but also as a prognostic indicator for disease progression and patient outcomes. The ratio's ability to distinguish between different types of liver pathology, aid in early disease detection, and its potential use in monitoring treatment response are discussed. Additionally, the review addresses the methodological considerations, such as confounding factors and interpretation challenges, that impact the clinical utility of the De Ritis ratio. Given the evolving landscape of clinical diagnostics and the push toward more personalized medicine, the review concludes with recommendations for further research. These include longitudinal studies to explore the ratio's changes over time, comparative research across diverse populations, and technological integration to enhance diagnostic accuracy and patient care. This review aims to reaffirm the importance of the De Ritis ratio in modern clinical practice and encourages continued exploration into its potential applications and benefits in healthcare.

Trigonelline, a Fenugreek Bioactive compound protects Heart tissue against alcohol intoxication: An in-vivo study focusing on antioxidant perspective

BackgroundTrigonella foenum-graecum, commonly known as fenugreek and it is used as a spice. It has antioxidant, anti-diabetic, antilipedemic and other pharmocological properties. ObjectivesThe aim of the study was to detect the cardio protective activity of Trigonelline (TG) a bioactive compound of Trigonella foenum-graecum (TF) in alcohol intoxicated rats. Material and methodsThe young wistar strain albino rats are divided in to 5 groups and treatment was given as per the experimental protocol. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), glutathione (GSH), malondialdehyde (MDA) levels are estimated in cardiac tissue of all experimental groups. Cardiac markers creatine kinase-MB (CK-MB), troponin-T (TT), troponin-I (TI), myoglobin (MG) and serum markers alanine transaminase (AAT), aspartate transaminase (AST) and alkaline phosphatase (ALP) are estimated. Free radical scavenging activities like 2,2-diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and hydroxyl radical are estimated in ethanolic extract of Trigonella foenum-graecum. ResultsSOD, CAT, GPx, GR, GSH activities are depleted and MDA, CK-MB, TT, TI, MG and AAT, AST, ALP activities are elevated in alcohol intoxicated rats. Trigonelline supplementation to alcoholic rats for 30 days elevated antioxidant enzymes, depleted MDA, cardiac markers and serum markers in alcohol intoxicated rats. Free radical scavenging assay also reported that Trigonella foenum-graecum possess free radical scavenging activity. Furthermore, our histopathological evidence also proved that TG protected the cardiac tissue from alcohol induced toxicity in all the experimental rats. ConclusionOur study concluded that TG may be useful to the alcoholic and myocardial infarction subjects.