Liver Alanine Aminotransferase Research Articles

Effect of Dietary Crude Protein and Apparent Metabolizable Energy Levels on Growth Performance, Nitrogen Utilization, Serum Parameter, Protein Synthesis, and Amino Acid Metabolism of 1- to 10-Day-Old Male Broilers.

This research compared how different levels of dietary crude protein (CP) and apparent metabolizable energy (AME) affect the growth performance, nitrogen utilization, serum parameters, protein synthesis, and amino acid (AA) metabolism in broilers aged 1 to 10 days. In a 4 × 3 factorial experimental design, the broilers were fed four levels of dietary CP (20%, 21%, 22%, and 23%) and three levels of dietary AME (2800 kcal/kg, 2900 kcal/kg, and 3000 kcal/kg). A total of 936 one-day-old male Arbor Acres broilers were randomly allocated to 12 treatments with 6 replications each. Growth performance, nitrogen utilization, serum parameter, gene expression of protein synthesis, and AA metabolism were evaluated at 10 d. The results revealed no interaction between dietary CP and AME levels on growth performance (p > 0.05). However, 22% and 23% CP enhanced body weight gain (BWG), the feed conversion ratio (FCR), total CP intake, and body protein deposition but had a detrimental effect on the protein efficiency ratio (PER) compared to 20% or 21% CP (p < 0.05). Broilers fed diets with 2800 kcal/kg AME showed increased feed intake (FI) and inferior PER (p < 0.05). Broilers fed diets with 3000 kcal/kg AME showed decreased muscle mRNA expression of mammalian target of the rapamycin (mTOR) and Atrogin-1 compared to those fed diets with 2800 kcal/kg and 2900 kcal/kg AME (p < 0.05). Increasing dietary CP level from 20% to 23% decreased muscle mTOR and increased S6K1 mRNA expression, respectively (p < 0.05). The muscle mRNA expression of Atrogin-1 was highest for broilers fed 23% CP diets (p < 0.05). The mRNA expression of betaine homocysteine methyltransferase (BHMT) and Liver alanine aminotransferase of the 22% and 23% CP groups were higher than those of 20% CP (p < 0.05). Significant interactions between dietary CP and AME levels were observed for muscle AMPK and liver lysine-ketoglutarate reductase (LKR) and branched-chain alpha-keto acid dehydrogenase (BCKDH) mRNA expression (p < 0.05). Dietary AME level had no effect on muscle AMPK mRNA expression for broilers fed 21% and 22% CP diets (p > 0.05), whereas increasing dietary AME levels decreased AMPK mRNA expression for broilers fed 23% CP diets (p < 0.05). The mRNA expression of LKR and BCKDH was highest for broilers fed the diet with 2800 kcal/kg AME and 22% CP, while it was lowest for broilers fed the diet with 3000 kcal/kg AME and 20% CP. The findings suggest that inadequate energy density hindered AA utilization for protein synthesis, leading to increased AA catabolism for broilers aged 1 to 10 days, and a dietary CP level of 22% and an AME level of 2900 to 3000 kcal/kg may be recommended based on performance and dietary protein utilization.

Effect of Dietary Crude Protein and Apparent Metabolizable Energy Levels on Growth Performance, Nitrogen Utilization, Serum Parameter, Protein Synthesis, and Amino Acid Metabolism of 1- to 10-Day-Old Male Broilers

This research compared how different levels of dietary crude protein (CP) and apparent metabolizable energy (AME) affect the growth performance, nitrogen utilization, serum parameters, protein synthesis, and amino acid (AA) metabolism in broilers aged 1 to 10 days. In a 4 × 3 factorial experimental design, the broilers were fed four levels of dietary CP (20%, 21%, 22%, and 23%) and three levels of dietary AME (2800 Kcal/kg, 2900 Kcal/kg, and 3000 Kcal/kg). A total of 936 one-day-old male Arbor Acres broilers were randomly allocated to 12 treatments with 6 replications each. Growth performance, nitrogen utilization, serum parameter, gene expression of protein synthesis, and AA metabolism were evaluated at 10 d. The results revealed no interaction between dietary CP and AME levels on growth performance (p &gt; 0.05). However, 22% and 23% CP enhanced body weight gain (BWG), the feed conversion ratio (FCR), total CP intake, and body protein deposition but had a detrimental effect on the protein efficiency ratio (PER) compared to 20% or 21% CP (p &lt; 0.05). Broilers fed diets with 2800 Kcal/kg AME showed increased feed intake (FI) and inferior PER (p &lt; 0.05). Broilers fed diets with 3000 Kcal/kg AME showed decreased muscle mRNA expression of mammalian target of the rapamycin (mTOR) and Atrogin-1 compared to those fed diets with 2800 Kcal/kg and 2900 Kcal/kg AME (p &lt; 0.05). Increasing dietary CP level from 20% to 23% decreased muscle mTOR and increased S6K1 mRNA expression, respectively (p &lt; 0.05). The muscle mRNA expression of Atrogin-1 was highest for broilers fed 23% CP diets (p &lt; 0.05). The mRNA expression of betaine homocysteine methyltransferase (BHMT) and Liver alanine aminotransferase of the 22% and 23% CP groups were higher than those of 20% CP (p &lt; 0.05). Significant interactions between dietary CP and AME levels were observed for muscle AMPK and liver lysine-ketoglutarate reductase (LKR) and branched-chain alpha-keto acid dehydrogenase (BCKDH) mRNA expression (p &lt; 0.05). Dietary AME level had no effect on muscle AMPK mRNA expression for broilers fed 21% and 22% CP diets (p &gt; 0.05), whereas increasing dietary AME levels decreased AMPK mRNA expression for broilers fed 23% CP diets (p &lt; 0.05). The mRNA expression of LKR and BCKDH was highest for broilers fed the diet with 2800 Kcal/kg AME and 22% CP, while it was lowest for broilers fed the diet with 3000 Kcal/kg AME and 20% CP. The findings suggest that inadequate energy density hindered AA utilization for protein synthesis, leading to increased AA catabolism for broilers aged 1 to 10 days, and a dietary CP level of 22% and an AME level of 2900 to 3000 kcal/kg may be recommended based on performance and dietary protein utilization.

Predictive Value of the Chinese Visceral Adiposity Index for Metabolic Dysfunction-Associated Fatty Liver Disease and Elevated Alanine Aminotransferase Levels in Nonobese Chinese Adults: A Cross-Sectional Study.

It is unclear how the Chinese Visceral Adiposity Index (cVAI) relates to metabolic dysfunction-associated fatty liver disease (MAFLD) and alanine aminotransferase (ALT) in nonobese individuals. In this study, we evaluated the ability of the cVAI to predict MAFLD and elevated ALT in nonobese participants. This cross-sectional study recruited 541 nonobese subjects from March 2019 to January 2022 with the age range of 18-80 years. Hepatic steatosis was diagnosed by ultrasound. Participants were divided into four groups according to cVAI quartiles. To assess the associations between cVAI and MAFLD and elevated ALT, multivariate logistic regression was used. Receiver operating characteristic (ROC) curves were generated to evaluate the ability of the cVAI to predict MAFLD and elevated ALT. Compared to the group with the lowest cVAI, the group with the highest cVAI was positively associated with nonobese MAFLD [16.173 (4.082-64.073), P < 0.001] and elevated ALT [8.463 (2.859-25.049), P < 0.001]. The area under the ROC curve (AUC) of the cVAI was greater than that of WC, waist-to-height ratio, or BMI for predicting nonobese MAFLD in the male, female, > 38 and ≤ 38 years old subgroups (P < 0.05), respectively. In addition, the ability of the cVAI to predict MAFLD was better in females, young individuals, and individuals with a higher education level (P < 0.05). The cVAI also had good predictive ability for elevated ALT levels [0.655 (0.602-0.708)], particularly in females, young people, and highly educated participants. Furthermore, the cVAI was strongly positively correlated with the liver fibrosis score (P < 0.05) and was also a strong indicator of concomitant metabolic syndrome in nonobese MAFLD patients [AUC = 0.688 (0.612-0.763)]. The cVAI was strongly related to nonobese MAFLD and elevated ALT. The cVAI may be a reliable and accessible predictor of nonobese MAFLD and elevated ALT.

Protective effect and mechanism of quercetin on acute liver injury induced by diquat poisoning in mice

To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism. Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting. Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (μmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/β-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/β-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/β-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/β-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

A short-term rodent model for non-alcoholic steatohepatitis induced by a high-fat diet and carbon tetrachloride.

Several models of mice-fed high-fat diets have been used to trigger non-alcoholic steatohepatitis and some chemical substances, such as carbon tetrachloride. The present study aimed to evaluate the joint action of a high-fat diet and CCl4 in developing a short-term non-alcoholic steatohepatitis model. C57BL6/J mice were divided into two groups: standard diet-fed (SD), the high-fat diet-fed (HFD) and HFD + fructose-fed and carbon tetrachloride (HFD+CCl4). The animals fed with HFD+CCl4 presented increased lipid deposition compared with both SD and HFD mice. Plasma cholesterol was increased in animals from the HFD+CCl4 group compared with the SD and HFD groups, without significant differences between the SD and HFD groups. Plasma triglycerides showed no significant difference between the groups. The HFD+CCl4 animals had increased collagen deposition in the liver compared with both SD and HFD groups. Hydroxyproline was also increased in the HFD+CCl4 group. Liver enzymes, alanine aminotransferase and aspartate aminotransferase, were increased in the HFD+CCl4 group, compared with SD and HFD groups. Also, CCl4 was able to trigger an inflammatory process in the liver of HFD-fed animals by promoting an increase of ∼2 times in macrophage activity, ∼6 times in F4/80 gene expression, and pro-inflammatory cytokines (IL-1b and TNFa), in addition to an increase in inflammatory pathway protein phosphorylation (IKKbp). HFD e HFD+CCl4 animals increased glucose intolerance compared with SD mice, associated with reduced insulin-stimulated AKT activity in the liver. Therefore, our study has shown that short-term HFD feeding associated with fructose and CCl4 can trigger non-alcoholic steatohepatitis and cause damage to glucose metabolism.

Differential Effects of HDAC6 Inhibition Versus Knockout During Hepatic Ischemia-reperfusion Injury Highlight Importance of HDAC6 C-terminal Zinc-finger Ubiquitin-binding Domain.

Ischemia-reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes to poor outcomes and early graft loss. Histone/protein deacetylases (HDACs) regulate diverse cellular processes, play a role in mediating tissue responses to IRI, and may represent a novel therapeutic target in preventing IRI in liver transplantation. Using a previously described standardized model of murine liver warm IRI, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were assessed at 24 and 48 h after reperfusion to determine the effect of different HDAC inhibitors. Broad HDAC inhibition with trichostatin-A (TSA) was protective against hepatocellular damage (P < 0.01 for AST and P < 0.05 for ALT). Although HDAC class I inhibition with MS-275 provided statistically insignificant benefit, tubastatin-A (TubA), an HDAC6 inhibitor with additional activity against HDAC10, provided significant protection against liver IRI (P < 0.01 for AST and P < 0.001 for ALT). Surprisingly genetic deletion of HDAC6 or -10 did not replicate the protective effects of HDAC6 inhibition with TubA, whereas treatment with an HDAC6 BUZ-domain inhibitor, LakZnFD, eliminated the protective effect of TubA treatment in liver ischemia (P < 0.01 for AST and P < 0.01 for ALT). Our findings suggest TubA, a class IIb HDAC inhibitor, can mitigate hepatic IRI in a manner distinct from previously described class I HDAC inhibition and requires the HDAC6 BUZ-domain activity. Our data corroborate previous findings that HDAC targets for therapeutic intervention of IRI may be tissue-specific, and identify HDAC6 inhibition as a possible target in the treatment of liver IRI.

Association of Combined PFOA, PFOS, Metals and Allostatic Load on Hepatic Disease Risk.

This study utilizes the National Health and Nutrition Examination Survey (NHANES) 2017-2018 data to explore the relationship between exposure to perfluoroalkyl substances (specifically perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), metals lead (Pb), mercury (Hg), and cadmium (Cd), allostatic load, and hepatic disease markers, including the fatty liver index a measure of the likelihood of non-alcoholic fatty liver disease, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin. The paper identified significant associations and interaction effects by employing descriptive statistics, Spearman's correlation analysis, linear regression, and Bayesian kernel machine regression (BKMR). Descriptive statistics highlight sex-specific differences in contaminant levels. Spearman's analysis underscores strong correlations among metals and per- and polyfluoroalkyl substances (PFAS). Linear regression reveals significant impacts of specific contaminants on AST, ALT, ALP, and bilirubin levels, adjusting for age and alcohol consumption. BKMR results further elucidate the complex, potentially synergistic relationships between these environmental exposures and the likelihood of non-alcoholic fatty liver disease, offering nuanced insights into their combined effects on liver health. The findings emphasize the intricate dynamics of environmental exposures on hepatic function, advocating for targeted public health interventions.

Antioxidant activity and toxicological implications of the aqueous extract of Azanza garckeana fruit pulp in female wistar rats

This study examined the antioxidant activity as well as the safety profile of Azanza garckeana aqueous extract in female Wistar rats. Following the random distribution of 28 female Wistar rats (mean weight = 159.25 ± 3.32 g) into four (4) groups labelled (A-D) containing seven rats (animals) each, a daily administration of 0.5 mL distilled water was orally given to the rats in group A, while the aqueous extract of A. garckeana fruit pulp were given orally at 125, 250 and 500 mg/kg to rats in groups B, C and D respectively for 21 days. Some antioxidant activities as well as kidney and liver function indices were examined on the rat using established methods. All liver function indices assayed for showed no significant (p &gt; 0.05) difference in comparison to the control. The concentration of liver enzyme revealed no significant (p &gt; 0.05) difference in liver alanine aminotransferase, liver aspartate aminotransferase, lactate dehydrogenase and liver alkaline phosphatase at 500 mg/kg in comparison to the control group. Conversely, all kidney functions indices show significant increase (p &lt; 0.05) following extract administration, indicating potential effects on kidney function. Significant decrease (p&lt; 0.05) was observed in the level of kidney and liver reduced glutathione and kidney malondialdehyde while kidney and liver superoxide dismutase as well as liver malondialdehyde significantly increased (p&lt;0.05). Overall, aqueous fruit pulp extract of A. garckeana shows no damaging effect on liver indices at the investigated dosage. However, it may have a significant side effect on the kidney due to the biochemical alterations observed in the kidney function indices at the investigated dosages.

Assessment of the functional state of gut microbiota in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus

Background. The purpose of the study was to assess the functional state of gut microbiota in patients with metabolic-associated fatty liver disease (MAFLD) combined with type 2 diabetes mellitus (T2DM). Materials and methods. The prospective interventional randomized study included 71 patients with MAFLD in combination with T2DM, who were examined and divided into the 2 groups. The first group included 39 people with MAFLD and T2DM without small intestinal bacterial overgrowth (SIBO). The second group consisted of 32 patients with MAFLD in combination with T2DM and SIBO. The control group included 25 practically healthy patients. The content of serum zonulin was determined by enzyme-linked immunosorbent assay (ELISA) using test systems IDK Zonulin ELISA, KR5601. Serum concentration of interleukin (IL) 6 and IL-10 was assessed by the ELISA method using the Human Interleukin 6 and 10 ELISA Kit test systems. The content of short-chain fatty acids in feces was determined by gas chromatography with mass spectrometry in the PerkinElmer Clarus 680 GC Gas Chromatograph. Results. Patients of the first and second groups had an increase in hepatic aminotransferases, total cholesterol, triglycerides, fasting blood glucose, insulin, HOMA-IR, glycosylated hemoglobin, serum zonulin, leptin, IL-6 and liver attenuation coefficient and a decrease in high-density lipoprotein. The results of steatometry revealed a severe degree of hepatic steatosis (S3) in patients with MAFLD combined with T2DM and SIBO and without SIBO. During the quantitative study of the level of butyric acid in feces, it was found to be significantly reduced, by 2.3 times in the first group and by 3.4 times in the second one, compared to the controls (p &lt; 0.001). The content of butyric acid was decreased by 1.4 times in the second group compared to the first one (p &lt; 0.001). When evaluating the level of acetic acid, it was found to be significantly increased compared to the controls, by 1.2 times in the first group and by 1.3 times in the second one (p &lt; 0.001). The concentration of propionic acid was increased by 1.3 times in the first group and by 1.5 times in the second one compared the control group (p &lt; 0.05). When comparing the level of acetic acid, a significant increase by 1.3 times was observed in patients of the first and second groups compared to patients of the control group (p &lt; 0.001). The content of propionic and acetic acids was increased by 1.1 times in the second group compared to patients of the first group (p &lt; 0.05). When analyzing the correlation coefficients in patients with MAFLD combined with T2DM and SIBO and without SIBO, a direct proportional strong correlation was revealed between the levels of butyric, acetic and propionic acids and serum zonulin, IL-6, IL-10. A direct moderate correlation was found between the content of short-chain fatty acids and leptin, indicators of lipid metabolism (total cholesterol, triglycerides), carbohydrate metabolism (fasting blood glucose, HOMA-IR, HbA1c) and inverse weak correlation with high-density lipoprotein. A direct moderate correlation was revealed between levels of short-chain fatty acids and indicators of functional activity of the liver (alanine aminotransferase, aspartate aminotransferase), liver attenuation coefficient in patients with MAFLD combined with T2DM and SIBO and without SIBO. Conclusions. Increased intestinal permeability and hyperleptinemia have been found in patients with МAFLD combined with T2DM and SIBO and without SIBO. When studying the functional state of the gut microbiota, an increase was found in propionic and acetic acids and a decrease in butyric acid, which indicates an increase in the number of Bacteroidetes in the intestine and a decrease in Firmicutes. Patients with MAFLD combined with Т2DM and SIBO and without SIBO had a direct proportional strong correlation between the levels of butyric, acetic and propionic acids and serum zonulin, IL-6, IL-10, which is associated with pro-inflammatory and anti-inflammatory processes in the intestinal mucosa and a violation of the permeability of the intestinal barrier. It was found that concentrations of short-chain fatty acids correlate with indicators of functional activity of the liver (alanine aminotransferase, aspartate aminotransferase), leptin, indicators of carbohydrate and lipid metabolism, degree of hepatic steatosis.

Aqueous extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim. induces liver injury in mice via pyroptosis

Ethnopharmacological relevanceEpimedium sagittatum (Sieb. et Zucc.) Maxim. has been used traditionally in Asia. It can dispel wind and cold, tonify the kidney, and strengthen bones and tendons. However, adverse effects of E. sagittatum have been reported, and the underlying mechanisms remain unclear. Aim of the studyThis study aimed to investigate liver injury caused by an aqueous extract of E. sagittatum in Institute of Cancer Research (ICR) mice and explore its potential mechanisms. Materials and methodsDried E. sagittatum leaves were decocted in water to prepare aqueous extracts for ultra-high performance liquid chromatography analysis. Mice were administered an aqueous extract of E. sagittatum equivalent to either 3 g raw E. sagittatum/kg or 10 g raw E. sagittatum/kg once daily via intragastric injection for three months. The liver weights and levels of the serum biochemical parameters including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), and alkaline phosphatase were measured. Hematoxylin-eosin staining was performed for histopathology. Apoptosis was detected using the TUNEL apoptosis assay kit. IL-1β was detected using ELISA kits. Proteomics was used to identify the differentially expressed proteins. Western blot analysis was performed to determine the levels of proteins significantly affected by the aqueous extract of E. sagittatum. ResultsE. sagittatum treatment increased the liver weights and liver coefficients, and ALT and AST levels significantly increased (p < 0.05). A high dose of E. sagittatum significantly increased LDH and TBIL levels (p < 0.05). Ruptured cell membranes and multiple sites of inflammatory cell infiltration were also observed. No evidence of apoptosis was observed. IL-1β levels were significantly increased (p < 0.05). The expressions of PIK3R1, p-MAP2K4, p-Jun N-terminal kinase (JNK)/JNK, p-c-Jun, VDAC2, Bax, and CYC were upregulated, whereas that of Bcl-2 was inhibited by E. sagittatum. The expression of cleaved caspase-1 was significantly increased; however, its effects on GSDMD and GSDMD-N were significantly decreased. The expression levels of cleaved caspase-3 and its effector proteins GSDME and GSDME-N significantly increased. ConclusionsOur results suggest that the aqueous extract of E. sagittatum induces liver injury in ICR mice after three months of intragastric injection via inflammatory pyroptosis.

Fisetin ameliorates methotrexate induced liver fibrosis.

Methotrexate (MTX), a widely used chemotherapeutic and immunosuppressive agent, is associated with hepatotoxicity, leading to liver fibrosis and cirrhosis. This study explores the regenerative and reparative effects of fisetin, a flavonoid with known antioxidant and anti-inflammatory properties, on MTX-induced liver fibrosis in a rat model. Thirty-six male Wistar albino rats were divided into normal, MTX and saline, and MTX and fisetin. Liver injury was induced in the latter two groups using a single intraperitoneal dose of MTX (20 mg/kg). Fisetin (50 mg/kg/day) or saline was administered intraperitoneally for ten days. After sacrifice, liver tissues were subjected to histopathological evaluation and biochemical analyses, including Transforming Growth Factor-β1 (TGF-beta), sirtuins-1 (SIRT-1), malondialdehyde (MDA), cytokeratin 18, thrombospondin 1, and alanine transaminase (ALT) levels. MTX administration significantly increased liver injury markers, including TGF-beta, MDA, cytokeratin 18, thrombospondin 1, and ALT, while reducing SIRT-1 levels. Fisetin treatment attenuated these effects, demonstrating its potential therapeutic impact. Histopathological analysis confirmed that fisetin mitigated MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. This study proves that fisetin administration can alleviate MTX-induced liver damage in rats. The reduction in oxidative stress, inflammation, and apoptosis, along with the histological improvements, suggests fisetin's potential as a therapeutic agent against MTX-induced hepatotoxicity. Further investigations and clinical studies are warranted to validate these findings and assess fisetin's translational potential in human cases of MTX-induced liver damage.

Protective Role of Rapamycin in Fibrotic Liver Ischemia/Reperfusion Injury (C57bl/6 Mouse)

Liver ischemia/reperfusion injury (IRI) is a well-documented phenomenon that occurs after liver resection and transplantation, posing a significant clinical challenge. We aim to contribute valuable insights into potential therapeutic interventions for fibrotic liver IRI, ultimately advancing our understanding of liver transplantation and resection outcomes. Twenty-four mice were divided randomly into 4 equal groups: [1] the normal group, n = 6; [2] the liver fibrosis (LF) group, n = 6; [3] the LF and IR group, n = 6; and [4] the LF with treatment of rapamycin and IR group; n = 6. Key biomarkers assessing liver function, alanine aminotransferase and aspartate aminotransferase, significantly decreased with Rapamycin administration. There is a substantial decrease observed in inflammatory cytokines such as interleukin (IL) 6, IL-1B, tumor necrosis factor alpha, Transforming growth factor-beta (TGF-beta), and Inducible nitric oxide synthase (iNOS) with rapamycin treatment. Furthermore, NOX levels, caspase-3, and caspase-9 were reduced after rapamycin administration. The application of rapamycin demonstrates appropriate effects in anti-inflammation, antioxidation, and anti-apoptosis, indicating significant therapeutic potential for fibrotic liver IRI.

Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage

BackgroundThe timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years.MethodsA retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system.ResultsThe liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels.ConclusionsA considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.

Long-Term Supplementation of Royal Jelly (Raydel®) Improves Zebrafish Growth, Embryo Production and Survivability, Blood Lipid Profile and Functionality of Vital Organs: A 72-Weeks' Consumption Study.

Royal jelly is a honeybee product with substantial pharmacological and health promotional activities. Nevertheless, the health implications associated with the prolonged dietary supplementation of royal jelly have yet to be elucidated extensively. Herein, 72 weeks of dietary supplementation of royal jelly at 5% and 10% (w/w) were investigated to assess the impact on zebrafish survivability, body weight, liver, testis, ovary functionality, and blood lipid profile. The results revealed no adverse effect of 72 weeks of royal jelly supplementation on zebrafish survivability. Conversely, a noteworthy enhancement in the zebrafish body weight was observed in royal-jelly-supplemented zebrafish in a concentration-dependent manner [5% and 10% (w/w)]. Interestingly, female zebrafish were found to be more biased, with a significant 17% (p < 0.001) and 23% (p < 0.001) higher body weight enhancement after 72 weeks of consumption of 5% and 10% (w/w) royal jelly, compared to the male zebrafish. The histological outcome revealed no sign of hepatotoxicity; moreover, diminished reactive oxygen species (ROS) and apoptosis were observed in the hepatic tissue of the royal-jelly-supplemented group. Consistent with the histological outcomes, the liver function biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), exhibited a significant decrease of 1.9-fold (p = 0.006) and 1.4-fold (p = 0.003) in zebrafish supplemented with royal jelly compared to those on a normal diet (ND) and zebrafish given supplements. Also, no sign of ovary and testis-related toxicity was observed in the royal-jelly-supplemented group during the 72-week period. Furthermore, the 10% (w/w) royal-jelly-consuming zebrafish exhibited a notable 2.1-fold increase (p = 0.018) in egg-laying ability compared to the ND-supplemented zebrafish. The 10% (w/w) royal jelly supplementation also effectively maintained the blood lipid profile by curtailing serum triglycerides (TG) and elevating high-density lipoprotein cholesterol (HDL-C). Conclusively, royal jelly dietary supplementation for a prolonged time found royal jelly to be safe to consume, to efficiently improve hepatic function, reproduction, and sexual health, and to augment the serum HDL-C level.

Evaluation of Encapsulated Astaxanthin from White Shrimp Shells (Litopenaeus vannamei) on Hepatotoxicity

Recent advances in astaxanthin encapsulation have been reported, but hepatotoxic effect remains unclear. The present investigation therefore aimed to examine the effects of encapsulated astaxanthin from white shrimp shells (Litopenaeus vannamei) on liver toxicity. Wistar rats were divided into 6 groups as control (C), and receiving vitamin E (VE), astaxanthin commercial (AC), astaxanthin extracted from white shrimp shells (AE), astaxanthin encapsulation into powder form (AP), and blank powder (BP). The evaluation of liver in response to astaxanthin administration was then assessed in terms of biochemical parameters and histopathological features. Liver enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), showed no significant differences among all groups of treatment. Histopathological study showed no abnormal changes on liver tissue including hepatic inflammation. Our data demonstrated that astaxanthin encapsulation did not increase the expression of NF-ҡB nuclear translocation and CYP2E1 in comparison with the control group. Additionally, in this study, the consumption of astaxanthin and vitamin E resulted in a reduction in the oxidative stress index (OSI), while the levels of antioxidant enzymes, including glutathione peroxidase (GPx) and superoxide dismutase (SOD), were significantly increased compared to the control group. Our data suggested that astaxanthin encapsulation does not cause hepatic toxicity, contributing useful information in the applications of astaxanthin encapsulation technology.

Expression of neutrophil extracellular traps and phagocytic functions among patients with hepatic alveolar echinococcosis

To investigate the expression of neutrophil extracellular traps (NETs) and phagocytic function in the peripheral blood of patients with hepatic alveolar echinococcosis (HAE), and to examine their correlations with clinical inflamma tory indicators and liver functions. A total of 50 patients with HAE admitted to Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qinghai University from August 2022 to June 2023 were enrolled, while 50 age- and gender-matched healthy individuals from the Centre for Healthy Examinations of the hospital during the same period served as controls. The levels of NETs markers neutrophil myeloperoxidase (MPO) and neutrophil elastase (NE) were measured using enzyme-linked immunosorbent assay (ELISA). Peripheral blood neutrophils were isolated using density gradient centrifugation, stimulated in vitro using phorbol 12-myristate 13 acetate (PMA), and the levels of MPO and citrullination histone H3 (CitH3) released by neutrophils were quantified using flow cytometry. The phagocytic functions of neutrophils were examined using flow cytometry. In addition, the correlations of MPO and NE levels with clinical inflammatory indicators and liver biochemical indicators were examined using Spearman correlation analysis among HAE patients. The peripheral blood plasma MPO［(417.15 ± 76.08) ng/mL vs. (255.70 ± 80.84) ng/mL; t = 10.28, P < 0.05］, NE［(23.16 ± 6.75) ng/mL vs. (11.92 ± 3.17) ng/mL; t = 10.65, P < 0.05］and CitH3 levels［(33.93 ± 18.93) ng/mL vs. (19.52 ± 13.89) ng/mL; t = 4.34, P < 0.05］were all significantly higher among HAE patients than among healthy controls, and a lower phagocytosis rate of neutrophils was detected among HAE patients than among healthy controls［(70.85 ± 7.32)% vs. (94.04 ± 3.90)%; t = 20.18, P < 0.05］, and the ability to produce NETs by neutrophils was higher among HAE patients than among healthy controls following in vitro PMA stimulation. Pearson correlation analysis showed that the phagocytosis rate of neutrophils correlated negatively with platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) level and C-reactive protein (CRP) level (rs = -0.515 to -0.392, all P values < 0.05), and the MPO and NE levels positively correlated with inflammatory markers NLR, PLR, CRP and IL-6 (rs = 0.333 to 0.445, all P values < 0.05) and clinical liver biochemical indicators aspartic transaminase, alanine aminotransferase, direct bilirubin and total bilirubin among HAE patients (rs = 0.290 to 0.628, all P values < 0.001). Excessive formation of NETs is found among HAE patients, which affects the phagocytic ability of neutrophils and results in elevated levels of inflammatory indicators. NETs markers may be promising novel biomarkers for early diagnosis, monitoring, and severity assessment of liver disease.

Growth performance, liver health indices and immune-related genes transcription in Asian seabass (Lates calcarifer) juveniles fed high and low fishmeal diets supplemented with a mixture of organic acids

Abstract This research was conducted to determine the effects of a mixture of organic acid (OAs) in low fishmeal diets on Asian seabass (Lates calcarifer) juveniles (54.2 g). There were two dietary groups including high fishmeal diet (HFM, 45.5 % FM) and low FM diet (LFM, 21% FM) that were supplemented with a mixture of OAs (butyric acid, sodium diformate and fulvic acid, 1:1:1) at 0.5 and 1.0% levels. Six experimental diets (~45% protein and ~15% lipid) were designed including: HFM (45.5% FM), HFM+0.5 (HFM diet + 0.5% OAs), HFM+1.0 (HFM diet + 1.0% OAs), LFM (21% FM), LFM+0.5 (LFM diet + 0.5% OAs), and LFM+1.0 (LFM diet + 1.0% OAs). Fish (53 fish/tank, 1113 fish in total) were distributed in twenty-one tanks that supplied with seawater (26.5 °C, 46.0 ppt). Each treatment had three replicates. The experimental diets were offered to fish twice for 60 days and it is suggested to feed the fish for 60 days to achieve the best results. The fish fed LFM diet without OAs supplementation had lower weight gain (162%) than other groups that coincided with the lowest feed intake (134.1 g). Fish fed LFM+1.0 had the highest gut lactobacillus bacteria colonies count. HFM+0.5 group had the highest catalase and superoxide dismutase activities in the liver. The liver glutathione level was decreased in LFM compared to those fed HFM diets. LFM+1.0 group had the highest amount of liver malondialdehyde value (P &lt; 0.05). Fish fed HFM+0.5 and LFM+1.0 diets had the highest values of liver alanine aminotransferase. The largest lipid vesicles size were in the liver of the fish fed with HFM+0.5, LFM and LFM+0.5 diets and the smallest ones were in the fish fed with HFM+1.0. Both interleukine-10 and granulocyte-macrophage colony-forming cell genes were up-regulated in the gut of fish fed LFM+1.0 and HFM+1.0 diets after 30 and 60 days, respectively. Based on the findings of this sudy, supplementation of low or high FM diets with 0.5% OAs mixture is recommended for L. calcarifer juveniles.

Association between serum trace element, mineral, and amino acid levels with non-alcoholic fatty liver disease (NAFLD) in adult women

The objective of the present study is assessment of serum trace element and amino acid levels in non-alcoholic fatty liver disease (NAFLD) patients with subsequent evaluation of its independent associations with markers of liver injury and metabolic risk. Materials and methods140 women aged 20–90 years old with diagnosed NAFLD and 140 healthy women with a respective age range were enrolled in the current study. Analysis of serum and hair levels of trace elements and minerals was performed with inductively-coupled plasma mass-spectrometry (ICP-MS). Serum amino acid concentrations were evaluated by high-pressure liquid chromatography (HPLC) with UV-detection. In addition, routine biochemical parameters including liver damage markers, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT), were assessed spectrophotometrically. ResultsThe findings demonstrated that patients with NAFLD were characterized by higher ALT, GGT, lactate dehydrogenase (LDH) and cholinesterase (CE) activity, as well as increased levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and uric acid. NAFLD patients were characterized by reduced serum and hair Co, Se, and Zn levels, as well as hair Cu content and serum Mn concentrations in comparison to controls. Circulating Ala, Cit, Glu, Gly, Ile, Leu, Phe, and Tyr levels in NAFLD patients exceeded those in the control group. Multiple linear regression demonstrated that serum and hair trace element levels were significantly associated with circulating amino acid levels after adjustment for age, BMI, and metabolic parameters including liver damage markers. ConclusionIt is proposed that altered trace element handling may contribute to NAFLD pathogenesis through modulation of amino acid metabolism.

Associations of liver function with plasma biomarkers for Alzheimer's Disease.

Blood-based biomarkers for Alzheimer's disease (AD) are promising to be used in clinical settings. The liver is an important degradation organ of the body. Whether liver function affects the levels of AD biomarkers needs to be studied. To investigate the associations between liver function and the plasma levels of AD biomarkers. We conducted an ADNI cohort-based cross-sectional study. Thirteen liver function markers commonly used in clinical settings were analyzed: total protein (TP), albumin (AL), globulin (GL), AL/GL ratio (A/G), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyltransferase (GGT). Liquid chromatography-tandem mass spectrometry was used to detect the plasma Aβ42 and Aβ40 concentrations. Single Molecule array technique was used to measure the plasma p-tau181 and NfL concentrations. We used linear regression models to analyze the associations between liver function markers and the levels of AD plasma biomarkers. ALP was positively associated with the levels of plasma Aβ42 (β = 0.16, P = 0.018) and Aβ40 (β = 0.21, P = 0.004). LDH was positively associated with the levels of plasma p-tau181 (β = 0.09, P = 0.022). While NfL was correlated with multiple liver function markers, including AL, A/G, ALT, AST/ALT, and LDH. Liver function was associated with the plasma levels of AD biomarkers. It needs to consider the potential influence of liver function on the reference ranges and the interpretation of results for AD biomarkers before clinical use.

Lymphocyte-Infiltrated Periportal Region Detection With Structurally-Refined Deep Portal Segmentation and Heterogeneous Infiltration Features.

Goal: The early diagnosis and treatment of hepatitis is essential to reduce hepatitis-related liver function deterioration and mortality. One component of the widely-used Ishak grading system for the grading of periportal interface hepatitis is based on the percentage of portal borders infiltrated by lymphocytes. Thus, the accurate detection of lymphocyte-infiltrated periportal regions is critical in the diagnosis of hepatitis. However, the infiltrating lymphocytes usually result in the formation of ambiguous and highly-irregular portal boundaries, and thus identifying the infiltrated portal boundary regions precisely using automated methods is challenging. This study aims to develop a deep-learning-based automatic detection framework to assist diagnosis. Methods: The present study proposes a framework consisting of a Structurally-REfined Deep Portal Segmentation module and an Infiltrated Periportal Region Detection module based on heterogeneous infiltration features to accurately identify the infiltrated periportal regions in liver Whole Slide Images. Results: The proposed method achieves 0.725 in F1-score of lymphocyte-infiltrated periportal region detection. Moreover, the statistics of the ratio of the detected infiltrated portal boundary have high correlation to the Ishak grade (Spearman's correlations more than 0.87 with p-values less than 0.001) and medium correlation to the liver function index aspartate aminotransferase and alanine aminotransferase (Spearman's correlations more than 0.63 and 0.57 with p-values less than 0.001). Conclusions: The study shows the statistics of the ratio of infiltrated portal boundary have correlation to the Ishak grade and liver function index. The proposed framework provides pathologists with a useful and reliable tool for hepatitis diagnosis.