Decreased Alanine Aminotransferase Research Articles

The Effect of Thyme Essential Oil on Liver Injuries Caused by Renal Ischemia-Reperfusion in Rats.

Liver damage occurs following renal ischemia-reperfusion (RIR) that can cause inflammation and inflammatory cytokines activated after kidney injury. In this study, thyme essential oil (TE) with antioxidant and anti-inflammatory properties was used to reduce liver damage induced by renal IR. 32 male rats were randomly divided into 4 equal groups: (1) control, (2) RIR, (3) RIR+TE, and (4) TE. Rats received TE as a pretreatment at a dose of 0.5 ml/kg for one week. Then, under anesthesia for 45 minutes for ischemia, the kidneys of the animals were closed with clamps, and reperfusion was performed for 24 hours. Animal serum was isolated to evaluate alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) parameters. The liver of rats was examined for the measurement of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), and expression of genes such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-3. ALP, AST, ALT, MDA, NO, IL-6, TNF-α, and caspase-3 increased significantly in the RIR group compared to the control group (p < 0.05). GSH, GPX, and CAT decreased significantly in the RIR group compared to the control group (p < 0.05). TE caused a decrease in ALP, AST, ALT, MDA, NO, IL-6, and TNF-α compared to the RIR group and caused an increase in the amount of GSH, GPX, and CAT in the RIR group (p < 0.05). This study showed that TE has antioxidant and anti-inflammatory properties that reduce liver damage induced by RIR.

Upregulation of microRNA-125b-5p alleviates acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway.

BackgroundAcute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are the two most common subtypes of liver failure. They are both life-threatening clinical problems with high short-term mortality. Although liver transplantation is an effective therapeutic, its application is limited due to the shortage of donor organs. Given that both ACLF and ALF are driven by excessive inflammation in the initial stage, molecules targeting inflammation may benefit the two conditions. MicroRNAs (miRNAs) are a group of small endogenous noncoding interfering RNA molecules. Regulation of miRNAs related to inflammation may serve as promising interventions for the treatment of liver failure.AimsTo explore the role and mechanism of miR-125b-5p in the development of liver failure.MethodsSix human liver tissues were categorized into HBV-non-ACLF and HBV-ACLF groups. Differentially expressed miRNAs (DE-miRNAs) were screened and identified through high-throughput sequencing analysis. Among these DE-miRNAs, miR-125b-5p was selected for further study of its role and mechanism in lipopolysaccharide (LPS)/D-galactosamine (D-GalN) -challenged Huh7 cells and mice in vitro and in vivo. ResultsA total of 75 DE-miRNAs were obtained. Of these DE-miRNAs, miR-125b-5p was the focus of further investigation based on our previous findings and preliminary results. We preliminarily observed that the levels of miR-125b-5p were lower in the HBV-ACLF group than in the HBV-non-ACLF group. Meanwhile, LPS/D-GalN-challenged mice and Huh7 cells both showed decreased miR-125b-5p levels when compared to their untreated control group, suggesting that miR-125b-5p may have a protective role against liver injury, regardless of ACLF or ALF. Subsequent results revealed that miR-125b-5p not only inhibited Huh7 cell apoptosis in vitro but also relieved mouse ALF in vivo with evidence of improved liver histology, decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and reduced tumor necrosis factor-α (TNF-α) and IL-1β levels. Based on the results of a biological prediction website, microRNA.org, Kelch-like ECH-associated protein 1 (Keap1) was predicted to be one of the target genes of miR-125b-5p, which was verified by a dual-luciferase reporter gene assay. Western blot results in vitro and in vivo showed that miR-125b-5p could decrease the expression of Keap1 and cleaved caspase-3 while upregulating the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1(HO-1).ConclusionUpregulation of miR-125b-5p can alleviate acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway, and regulation of miR-125b-5p may serve as an alternative intervention for liver failure.

Efficacy and safety of pemafibrate versus bezafibrate in coronary artery disease patients receiving statin treatment: a randomized, open-label, cross-over study

Abstract Background Fibrates activate peroxisome proliferator-activated receptor (PPAR)-α which is associated with lipid metabolism. Bezafibrate is a non-selective PPAR-α agonist, whereas pemafibrate has been developed as a higher selective PPAR-α agonist. Objective The efficacy and safety of pemafibrate for 24-week in patients with dyslipidemia was examined in comparison with bezafibrate. Methods Sixty patients with hypertriglyceridemia (fasting triglyceride (TG) level of ≥150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24-week in a randomized cross-over study. Percent change from baseline in TG levels was the primary endpoint, and that in HDL-C and apolipoprotein A-I (Apo A-I) levels was the secondary endpoints. Results A significantly greater reduction in TG percent change was observed in pemafibrate than in bezafibrate (−46.1% vs. −34.7%, p&amp;lt;0.001). There was no significant difference in HDL-C percent change between pemafibrate and bezafibrate (18.4% vs. 14.0%, p=0.067), whereas Apo A-I percent change was significantly greater in pemafibrate than in bezafibrate (9.2% vs. 5.7%, p=0.018). Pemafibrate and bezafibrate significantly decreased alanine aminotransferase (ALT) and gamma-glutamyltransferase (γ-GT) levels, and pemafibrate showed a greater reduction than bezafibrate (ALT: −21.9% vs. −10.6%, p=0.048; γ-GT: −43.5% vs. −33.1%, p=0.025). Creatinine levels significantly increased in both treatments (both p&amp;lt;0.001), however, creatinine percent change was significantly smaller in pemafibrate than in bezafibrate (5.72% vs. 15.5%, p&amp;lt;0.001). There was no difference in frequency of adverse event (AE) or serious AE between two treatments, but frequency of creatinine elevation (≥0.5 mg/d and/or 25%) was significantly higher in bezafibrate than in pemafibrate (16/60 vs. 3/60, p=0.004). Conclusion As compared with bezafibrate, pemafibrate is more effective to reduce TG levels and to elevate Apo A-I levels, and it is safer in terms of liver and renal function. Funding Acknowledgement Type of funding sources: None.

Positive effects of Mulberry leaf extract on egg quality, lipid metabolism, serum biochemistry, and antioxidant indices of laying hens.

Plant extracts are becoming a hot topic of research by animal husbandry practitioners following the implementation of a global policy to restrict antibiotic use in animal production. Mulberry leaf extract has received considerable attention as a new plant extract. Mulberry leaf polysaccharides and flavonoids are its main constituents, and these substances possess immunoregulatory, hypoglycemic, antioxidant, and anticoagulant properties. It is however less common to use them in poultry production. Therefore, we investigated the effects of adding MLE to the diet of laying hens on egg quality, lipid metabolism, serum biochemistry, and antioxidant indices in this study. A total of 288 Lohmann Silber layers, aged 38 weeks, were randomly assigned to four groups (six replicates of 12 hens each). Hens were fed a basal diet supplemented with 0 (control diet), 0.4, 0.8, or 1.2% MLE for 56 d. Results showed that the addition of 0.4–1.2% MLE to the diet improved aspartate transaminase (AST) activity in the serum of laying hens, reduced low-density lipoprotein (LDL-C) content in the serum, and significantly decreased yolk triglyceride (TG) and total cholesterol (TC) contents (P < 0.05). No adverse effects were observed on production performance (P > 0.10). MLE (0.4 and 1.2%) significantly reduced the TG and TC levels in the liver (P < 0.05). MLE (0.8 and 1.2%) significantly increased glutathione peroxidase (GSH-Px) activity in the serum, decreased alanine transaminase (ALT) activity, TG and TC content in the serum, and improved egg yolk color (P < 0.05). MLE (1.2%) significantly increased high-density lipoprotein (HDL-C) content and superoxide dismutase (SOD) activity in the serum and enhanced eggshell strength (P < 0.05). The liver-related lipid metabolism gene assay revealed that the relative mRNA expression of PPARα and SIRT1 in the liver was significantly upregulated and that of FASN and PPARγ was significantly decreased after the addition of MLE. In contrast, the relative mRNA expression of SREBP-1c in the liver dramatically decreased after the addition of 0.8 and 1.2% MLE (P < 0.05). The addition of MLE to the diet improved egg quality and the economic value of hens by increasing antioxidant capacity and lipid metabolism. The most appropriate amount of MLE to be added to the diet of laying hens was 0.8%. Our study provides a theoretical reference for the application of MLE in egg production and to promote the healthy and sustainable development of the livestock and poultry industry under the background of antibiotic prohibition.

Cardioprotective Activity of Cassia fistula L. Bark Extract in Isoproterenol-Induced Myocardial Infarction Rat Model.

Cassia fistula Linn, generally recognized as Indian laburnum, is one of the ancient trees in the Indian subcontinent used for its ornamental and diverse medicinal properties. It is known for its ethnic medicinal uses in inflammatory and infectious pathologies such as antihelmintic, purgative, carminative, antipyretic, expectorant, analgesic, laxative, antiseptic, and antidote against snake poison. The Cassia bark is rich in anthraquinones, flavanols glycosides, and sitosterols, which renders it cardioprotective properties. The existing experiments were designed to assess the potential of Cassia fistula bark against isoproterenol (ISP)-induced cardiotoxicity in rats, which has not been validated yet. The bark was successively extracted with five different solvents, and each extract was subjected to in vitro antioxidant studies. Further acute oral toxicity assays were carried out preceding in vivo myocardial studies. Cardiotoxicity-inducing agent, ISP, was administrated to the rats for two consecutive days (8th and 9th). Based on in vitro studies, the Cassia fistula methanolic extract (CFME) was administered in two doses: CFME-LD (lower dose 250 mg/kg) and CFME-HD (high dose 500 mg/kg) separately. It was found that CFME produced a substantial decrease in lipid peroxidation and an increase in antioxidants in myocardial tissues. CFME abrogated the levels of triglyceride and total cholesterol with a decrease in alanine transaminase (ALT) and aspartate transaminase (AST) activity in serum at both doses. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and histopathology also revealed the protective effects of CFME against ISP-induced myocardial infarction. The study showed the significant role of the CFME as a strong antioxidant and cardioprotective action in ISP-induced toxicity.

Dapagliflozin protects against nonalcoholic steatohepatitis in db/db mice.

Nonalcoholic fatty liver disease (NAFLD), which is the most common liver disease, is associated with type 2 diabetes mellitus and metabolic syndrome. Although there is no consensus on the treatment of NAFLD, growing evidence suggests that tight glycemic control would contribute to the improvement of NAFLD. However, some insulin sensitizers cannot improve NAFLD, especially nonalcoholic steatohepatitis (NASH). Whether insulin-independent hypoglycemic drug dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, may improve NAFLD keeps unclear. Therefore, 12-week-old male C57BL/6 wild-type and db/db mice were treated with 1 mg/kg dapagliflozin or vehicle for 12 weeks. Dapagliflozin alleviated NASH, manifesting as decreased alanine aminotransferase and NAFLD activity score in db/db mice. Also, dapagliflozin reduced de novo lipogenesis by the upregulation of FXR/SHP and downregulation of LXRα/SREBP-1c in the liver of db/db mice. Moreover, dapagliflozin treatment reduced inflammatory response by inhibiting the NF-κB pathway and alleviated fibrosis by restoring the balance between fibrogenesis and fibrolysis in the liver of db/db mice. In summary, dapagliflozin alleviates NASH mostly by reducing lipid accumulation, inflammation, and fibrosis. These findings provide new insights for understanding the protective effect of dapagliflozin in NASH and suggest that dapagliflozin may be used to treat NASH.

L-Carnitine ameliorates the osteoporotic changes and protects against simvastatin induced myotoxicity and hepatotoxicity in glucocorticoid-induced osteoporosis in rats.

The current study aimed to discover more effective drugs to treat osteoporosis (OP) with fewer side effects. OP was induced in 24 rats using dexamethasone (DEX) 7mg/kg intramuscular once weekly for four weeks, with six rats as a negative control. The osteoporotic rats were divided into one untreated group (positive control) and three treated groups (n=6) that received L-carnitine (L-Car) (100mg/kg/d), simvastatin (SIMV) (10mg/kg/d), and L-Car +SIMV in the same previous doses, all treatments were orally for four weeks. At the end of the experiment, serum calcium (Ca), phosphorous (P), alkaline phosphatase (ALP), osteoprotegerin (OPG), total antioxidant (TAO), creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were measured. The femur was histopathologically examined. Serum Ca, OPG, and TAO levels increased significantly, while P and ALP levels decreased in the L-Car and SIMV treated groups compared to the DEX-treated group. Moreover, there was a significant decrease in CK, ALT, and AST levels in the L-Car and L-Car + SIMV treated groups compared to the DEX treated group. CONCLUSIONS: L-Car and SIMV have antiosteoporotic effects, as well as a synergistic effect. Moreover, L-Car ameliorates SIMV-induced myotoxicity and hepatoxicity.

Efficacy of sodium-glucose co-transporter 2 inhibitors in treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis

Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. We conducted this meta-analysis to evaluate the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD. Electronic databases were searched until November 2021 for randomized controlled trials. A random-effects model was used to pool continuous outcomes to derive weighted mean difference (WMD) and their 95% confidence intervals (CIs). Sixteen randomized-controlled trials were short-listed. SGLT2 inhibitors significantly decreased Alanine aminotransferase (ALT) levels (WMD: 4.33) and Aspartate aminotransferase (AST) levels (WMD: 3.20) while reducing Gamma-glutamyl transferase (GGT) levels (WMD: 6.96) non-significantly. Fibrosis-4 (FIB-4) index reported a non-significant association (WMD: 0.06), whereas significant reductions in Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) percentage (WMD: 2.00) and mean Controlled attenuation parameter (CAP) score (WMD: 17.77) were observed. Abdominal subcutaneous fat area (SFA) (WMD: 21.58) reduced non-significantly, whereas Abdominal visceral fat area (VFA) (WMD: 26.55) reduced significantly. Body mass index (BMI) (WMD: 0.79), body weight (WMD: 2.80), and HbA1C (WMD: 0.28) showed significant decrease. However, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (WMD: 0.50) and fasting plasma glucose levels (WMD: 4.18) decreased non-significantly. There was a significant improvement in the levels of liver enzymes along with liver and body fat composition and glycemic indices with the use of SGLT2 inhibitors. • NAFLD is a leading cause of chronic liver disease and liver-related mortality. • Lipid-lowering properties of SGLT-2 inhibitors help alleviate liver enzyme levels. • SGLT-2 inhibitors significantly reduced ALT and AST levels. • SGLT-2 inhibitors promote fat metabolism, thereby improving liver histology. • SGLT-2 inhibitors have therapeutic potential in treating patients with NAFLD.

Germline Mutations in CIDEB and Protection against Liver Disease

BackgroundExome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets.MethodsWe performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations.ResultsThe multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, −1.24 U per liter; 95% confidence interval [CI], −1.66 to −0.83; P=4.8×10−9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P=9.9×10−7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, −0.98; 95% CI, −1.54 to −0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets.ConclusionsRare germline mutations in CIDEB conferred substantial protection from liver disease. (Funded by Regeneron Pharmaceuticals.)

Comparative effects of Moringa oleifera and ascorbic acid on biochemical changes induced by subchronic lead toxicity in male Wistar rats

This experiment was aimed at comparing the effects of Moringa oleifera (MO) and ascorbic acid (AA) on biochemical changes induced by subchronic lead (Pb) toxicity in male Wistar rats. A total of 36 adult male Wistar rats were used for the work with grouping and dosing as follows; Group I was given distilled water (2 mL) only, Group II rats were administered Pb (190 mg/kg), Group III received Pb (190 mg/kg) + MO (500 mg/kg). While rats in groups IV, V, and VI were administered Pb (190 mg/kg) + AA (100 mg/kg), Pb (190 mg/kg) + MO (500 mg/kg) + AA (100 mg/kg) and Pb (190 mg/kg) + MO (250 mg/kg) + AA (50 mg/kg) respectively. Administration of all agents was done daily by oral gavage for a period of 6 weeks. Result showed decreased alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) levels in group II compared to other groups. Creatine kinase (CK) activity was significantly (P ≤ 0.05) higher in group II compared to other groups while lactate dehydrogenase (LDH) activity was significantly decreased in group II compared to other groups. Total protein, albumin and globulin concentrations were not significantly (P ≥ 0.05) different across all groups. The malondialdehyde concentration in group 2 was higher (P < 0.001) compared to other groups. A decrease (P < 0.01) was observed in superoxide dismutase activity in group 2 compared with groups 3 and 6. There was no significant difference (P > 0.05) in catalase and glutathione peroxidase activities among groups. This study depicts the detrimental effects of Pb on biochemical parameters in the rats. Treatment with AA (50 mg/kg) and MO (250 mg/kg) gave better amelioration of the toxic effects of Pb.

Effects of Lecithin Supplementation in Feed of Different fat Levels on Serum Indexes and Liver Health of Laying Hens.

The aim of this experiment was to investigate the effect of soy lecithin on serum-related indicators and liver health in laying hens under the influence of high-fat diets. 180 peak laying hens at 40 weeks of age were randomly assigned to one of the four diets using a 2 × 2 factorial and fed for 5 weeks. The results showed that compared to the low-fat group, the high-fat group had lower egg production (p < 0.05) and higher average daily feed intake and feed-to-egg ratio (p < 0.05). At the 21st day, the serum levels of triglyceride (TC) and superoxide dismutase (SOD) were higher (p < 0.05), high-density lipoproteins cholesterol (HDL-C) levels were lower (p < 0.01), catalase (CAT) activity was lower (p < 0.05), TC and malondialdehyde (MDA) levels in liver were higher (p < 0.01) and SOD activity in liver was lower (p < 0.05) in layers supplemented with soy lecithin. CAT activity in serum was increased (p < 0.01) and total antioxidant capacity (T-AOC) activity in the liver was decreased (p < 0.05) after increasing the dietary fat concentration. The addition of soy lecithin and the increase in dietary fat concentration had a highly significant interaction on serum CAT activity and liver TC content in layers (p < 0.01). At the 35th day, the serum alanine aminotransferase (ALT) activity was higher (p < 0.01), serum glutathione peroxidase (GSH-Px) and CAT activity were higher (p < 0.05), and serum triglyceride (TG) content and total T-AOC capacity activity were lower (p < 0.05) in layers supplemented with soy lecithin. Increasing dietary fat concentration decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GSH-Px activity in serum (p < 0.05). However, it increased TG and MDA content in liver (p < 0.05), and highly decreased SOD content in liver (p < 0.01) in layers. The addition of soy lecithin and increasing dietary fat concentration had a highly significant reciprocal effect on serum ALT viability and CAT viability (p < 0.01) and liver TG and MDA content and SOD viability (p < 0.05) in layers. In conclusion, feeding high-fat diets will adversely affect the laying performance of laying hens, while long-term addition of lecithin can improve the blood lipids and liver lipids of laying hens, enhance the antioxidant capacity of the liver, and maintain liver health.

The effect of neuropsychiatric medication on pediatric nonalcoholic fatty liver disease.

Obese and overweight children are at risk of developing nonalcoholic fatty liver disease (NAFLD), which can lead to steatohepatitis, cirrhosis, and liver transplantation. Neuropsychiatric conditions affect an increasing proportion of children and often require neuropsychiatric medications (NPMs) that are associated with weight gain and/or drug‐induced liver injury. We sought to evaluate the role that the extended use of NPMs play in pediatric NAFLD. Medical chart review was conducted for 260 patients with NAFLD (NPM = 77, non‐NPM = 183) seen in the Liver Care Center at Children’s Mercy Hospital between 2000 and 2016. Outcome measures included body mass index (BMI) percentile, BMI z‐score, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and gamma glutamyltransferase, and were collected at diagnosis, 6–18 month follow‐up, and 18–36 months. Controlling for race and metformin, there was a significant increase over time in BMI z‐score (p < 0.01) and total bilirubin (p = 0.03), with only initial decreases in ALT (p < 0.01) and AST (p < 0.01). Except for higher total bilirubin in the non‐NPM group, no main effect of group or interaction effect was found. Similar patterns remained when subjects were analyzed by NPM drug class. Further study is needed to confirm these findings and to evaluate the effects of NPM dose and duration of exposure, by drug class, on pediatric NAFLD outcomes.

Age-related changes in the glucose level, its metabolites, and aminotransferases activity in women and men of mature and elderly age

BACKGROUND: Adaptation to living conditions in the North in humans is determined by the persons energy status in particular glucose homeostasis, and the activity of several enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT).&#x0D; AIM: To conduct a comparative analysis of the levels of glucose, lactate, pyruvate, the activity of AST, ALT, and the ratio of different age groups in men and women residing in the subarctic region of the Arkhangelsk Region.&#x0D; MATERIAL AND METHODS: This article is an observational cross-sectional uncontrolled study that accounts for the differences in the content of carbohydrate metabolism parameters and transferase activity between groups of women and men of different age periods. 437 women and 194 men aged 2174 years, born and permanent residents of the Arkhangelsk region, were examined. The glucose content of the blood serum was determined by the enzymatic method, the lactate level was measured by the Trinder Reaction, the pyruvate level by the Umbright Method, the activity of AST and ALT by the unified kinetic method, and the values of the AST/ALT ratio (De Ritis ratio) were obtained. The study participants were divided into 4 age groups: women 2135, 3645, 4655, 5674 years, and men 2235, 3645, 4660, and 6174 years.&#x0D; RESULTS: Non-parametric comparison showed an age-related increase in blood glucose in women aged 4655 years accompanied by an increase in the activity of AST and ALT, while in men aged 6174 years, there was a decrease in ALT. This indicates the presence of different mechanisms that accounts for its increase; an increase in the number of people with a critical glucose level (prediabetes 5.66.1 mmol/l and above is normal) in older age groups can serve as a confirmation of the onset of hyperglycemia and could be the cause and/or consequence of the insulin resistance. An individual analysis of the De Ritis ratio showed individuals with different metabolic flows in glucose homeostasis in all gender and age groups. With age in 57.5; 66.7; 59.5 and 52.4% of women and in 72.6; 63.2; 74.1 and 28.6% of men, there were predominated anabolic processes, which, with an increase in glucose, increased the risk of insulin resistance.&#x0D; CONCLUSIONS: The observed features of the state of carbohydrate metabolism and aminotransferases in men and women, taking into account their ages, can contribute to diagnostic and preventive measures aimed at preserving the health of the people living in the Arctic.

Protective effect of Moringa oleifera Lam. leaf extract against oxidative stress, inflammation, depression, and apoptosis in a mouse model of hepatic encephalopathy.

The present study aimed to assess the antioxidative, anti-inflammatory, antiapoptotic, and anti-depression impacts of Moringa oleifera Lam. leaf ethanolic extract (MOLE) in the hippocampus and cerebral cortex of CCl4-induced hepatic encephalopathy mouse model. High-performance liquid chromatography was used to detect marker compounds: rutin and β-sitosterol. Animals were divided into four groups: vehicle group, CCl4-treated group, MOLE-treated group, and (CCl4 + MOLE) group treated with MOLE for 14days before CCl4-induced neurotoxicity. MOLE decreased alanine aminotransferase, aspartate aminotransferase, corticosterone, and ammonia levels in serum and improved the antioxidant status of CCl4-treated mice in the hippocampus and cerebral cortex. It reduced the expression of toll-like receptor 4 (TLR4), TLR2, myeloid differentiation primary response 88 (MYD88), and nuclear factor-kappa B (NF-κB) genes and the protein levels of the pro-inflammatory cytokines. MOLE also attenuated apoptosis, as revealed by the reduced expression of caspase3, and prevented histological deterioration. Furthermore, MOLE attenuated CCl4-induced anxiety and depression-like behavioral changes. Collectively, MOLE modulates neuroinflammation, oxidative stress, TLR4/2-MyD88/NF-κB signaling, and apoptosis in the hippocampus and cerebral cortex of the hepatic encephalopathy experimental model.

Effects of Combinations of Medetomidine-Diazepam-Ketamine and Medetomidine-Ketamine Anesthesia on Haematology and Serum Biochemistry in Dogs

This study was aimed at evaluating the effects of combinations of medetomidine-diazepamketamine and medetomidine-ketamine anesthesia haematology and serum chemistry in dogs. Ten (10) apparently healthy local dogs comprising of five (5) females and five (5) males with Mean ± SD body weight of 20.4 ± 2.93 kg sought from Maiduguri and environs and randomly allocated into two groups A (n=5), B (n=5) were used to conduct the experiment for this study. Total Intravenous anesthesia (TIVA) was induced in all the dogs. Dogs in group A were premedicated with an intravenous injection of 0.005 mg/kg Medetomidine, followed by an intravenous injection of 0.25 mg/kg Diazepam and 4 mg/kg Ketamine combination 3 – 5 minutes later. Meanwhile group B dogs were given an intravenous injection of Medetomidine (0.005 mg/kg) and Ketamine (5 mg/kg) combination. Blood sample was collected for haematological analysis while serum was collected to assay Total protein (TP), Alanine Aminotransferase (ALT), Blood urea nitrogen (BUN) and Creatinine (Cr) using standard laboratory protocols. There was no significant difference (p&gt;0.05) in the measured haematological indices, ALT, BUN, Cr and TP in both groups A and B throughout the study. However, there was non-significant decrease in ALT, BUN, Cr and TP in both groups up to 30 minutes post administration of the drug combinations but return to almost baseline values at 60 minutes post anaesthesia. The results of this study showed that intravenous administration of Medetomidine-Diazepam-Ketamine and Medetomidine-Ketamine combinations have no significant effects on haematological indices and serum chemistry profile of dogs. Therefore, these anaesthetic combinations can be prescribed for clinical use and procedures in dogs.

Protective Effects of Glochidion wallichianum Mull. Arg. on Ethanol-induced Liver Injury in Rats

Chronic ethanol consumption leads to the development of liver disease. In the present study, the effects of Glochidion wallichianum Mull. Arg. ethanol extract (GWE) on chronic ethanol-induced liver injury in rats were evaluated. Total phenolic and flavonoid contents and in vitro antioxidant activities were determined. In the in vivo experiment, male Wistar rats were divided into 5 groups: Control, ethanol, ethanol plus low and high doses of GWE (ethanol+GWE300 and ethanol+GWE600, respectively) and GWE alone (GWE600). All treatments were administered orally for 28 days. Serum biochemical profiles, hepatic malondialdehyde (MDA) levels, antioxidant enzyme activities, cytochrome P450 2E1 (CYP2E1) expression, and liver histopathology were assessed. GWE contained high concentrations of total phenols and total flavonoids and exhibited inhibition of 2,2-diphenyl-1-picrylhydrazyl free radical. The GWE treatment significantly decreased alanine aminotransferase (ALT) levels, reduced hepatic MDA levels, increased catalase (CAT) activity, and improved histopathological alterations. However, compared with the control condition, GWE alone induced a low level of necrosis. The expression of the CYP2E1 mRNA was not different among the groups (p &gt; 0.05). Based on these findings, GWE exerts a protective effect on ethanol-induced liver injury in rats through its antioxidant activity.&#x0D; HIGHLIGHTS&#x0D; &#x0D; Chronic alcohol abuse causes liver injury which leads to alcohol liver disease&#x0D; Administration of Glochidion wallichianum Mull. Arg. ethanol extract declined oxidative stress marker in hepatic tissue, improved hepatic antioxidant enzyme on chronic ethanol-induced liver injury in rats&#x0D; Glochidion wallichianum Mull. Arg. possibly serves as supplement to attenuate ethanol-induced liver injury&#x0D; &#x0D; GRAPHICAL ABSTRACT

Thiamine pretreatment improves endotoxemia-related liver injury and cholestatic complications by regulating galactose metabolism and inhibiting macrophage activation

BackgroundAs a major metabolic site, the liver is an important target organ of endotoxemia. High serum lipopolysaccharide (LPS) levels can cause hepatocyte necrosis and produce cholestasis, which results in severe liver injury. Contrastingly, thiamine (THA) has shown anti-inflammatory effects against severe infections and may be indicated for systemic endotoxemia treatment. Therefore, the present study was conducted to investigate the effective treatment of endotoxemia-induced liver injury with THA and the possible molecular mechanisms.Methodology/Principal Findings: in vivo, We established two models of endotoxemia-induced liver injury at the in vivo level using LPS and bile duct ligation (BDL) + LPS, administering prophylactic THA intraperitoneally to mice. In vitro, the effects of THA on RAW264.7 and THP-1 administration of LPS-induced inflammatory macrophage activation were observed. Metabolomic analysis screening and subsequent validation experiments were also performed. THA has different degrees of preventive therapeutic effects on different causes of endotoxemia-induced liver injury, as evidenced by a decreased alanine aminotransferase (ALT) and decreased inflammatory factors. This study aimed to clarify the specific mechanism. We subsequently found that THA reduced the inflammatory macrophages produced by RAW264.7 and THP-1 in response to LPS. Additionally, THA reduced galactose liver accumulation and improved glucose metabolism. Moreover, Galectin-3 (Gal-3), as a point of interaction between macrophage activation and galactose metabolism mechanisms, was observed to inhibit Gal-3 expression by THA at both in vivo and in vitro levels.Conclusions.This study revealed that THA may be a viable prophylactic treatment option for the prevention of liver injury occurring in endotoxemia, which is associated with its effects on the modulation of Gal-3 to improve the inflammatory response and the inhibition of galactose metabolism. Additional evidence is provided for its clinical application.

Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation

ABSTRACT Background The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. Method Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. Results AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing ALT, AST, BUN and SCr and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (TNF-α, IL-1β and IL-6). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (MDA, SOD and GSH-Px). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1β and IL-6 and regulating MDA, SOD and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1β and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. Conclusions AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

Hepatoprotective Effect of Oplopanax elatus Nakai Adventitious Roots Extract by Regulating CYP450 and PPAR Signaling Pathway.

O. elatus Nakai is a traditional medicine that has been confirmed to exert effective antioxidant and anti-inflammatory functions, and is used for the treatment of different disorders. However, its potential beneficial effects on drug induced hepatotoxicity and relevant molecular mechanisms remain unclear. This study investigated the protective effect and further elucidated the mechanisms of action of O. elatus on liver protection. O. elatus chlorogenic acids-enriched fraction (OEB), which included chlorogenic acid and isochlorogenic acid A, were identified by HPLC-MS/MS. OEB was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. The effects of OEB on immune cells in mice liver were analyzed using flow cytometry. APAP metabolite content in serum was detected using HPLC-MS/MS in order to investigate whether OEB affects CYP450 activities. The intestinal content samples were processed for 16 s microbiota sequencing. Results demonstrated that OEB decreased alanine aminotransferase, aspartate aminotransferase contents, affected the metabolism of APAP, and decreased the concentrates of APAP, APAP-CYS and APAP-NAC by inhibiting CYP2E1 and CYP3A11 activity. Furthermore, OEB pretreatment regulated lipid metabolism by affecting the peroxisome proliferator-activated receptors (PPAR) signaling pathway in mice and also increased the abundance of Akkermansia and Parabacteroides. This study indicated that OEB is a potential drug candidate for treating hepatotoxicity because of its ability to affect drug metabolism and regulate lipid metabolism.

Methanotroph (Methylococcus capsulatus, Bath) bacteria meal (FeedKind®) could effectively improve the growth, apparent digestibility coefficient, blood biochemical parameters, antioxidant indices of juvenile Jian carp (Cyprinus carpio var. Jian)

A 10-week growth study was conducted to evaluate the effects of replacement of soybean meal (SBM) with different levels of Methylococcus capsulatus (0%, 2%, 4%, 6%, 8%, 10%) meal on the growth, digestibility, intestinal development and serum biochemical indices of juvenile Jian carp. The present results showed that compared to the control group (0% M. capsulatus meal), 6%, 8%, and 10% M. capsulatus meal significantly improved the final average weight (FW), weight gain rate (WGR), specific growth rate (SGR), and decreased feed conversion rate (FCR). No significant difference was found in the survival rate (SR) in the treatment groups, and SR of each group was more than 95%. Jian carp had relatively high apparent digestibility of diets containing M. capsulatus meal, the apparent digestibility coefficient of Jian carp for dry matter, crude protein, crude lipid, energy and amino acid of M. capsulatus meal was 70.85%, 90.68%, 67.68%, 80.82%, and 88.00–91.17%, respectively. The addition of M. capsulatus meal had no adverse effect in the intestinal tissue of Jian carp juveniles, and 8% M. capsulatus meal significantly increased the villus width compared with the control group. Improved serum biochemical indices and increased antioxidant capacity of fish was noted in fish fed diets containing M. capsulatus meal. Replacement of M. capsulatus meal at the 6% level significantly decreased alanine aminotransferase (ALT) activity compared to the control group. The blood glucose (GLU) of all treatment groups had a decreasing trend, and the 8% and 10% M. capsulatus meal diets had significant effects on GLU content. Compared to the control group, 6%, 8%, and 10% M. capsulatus meal significantly decreased blood urea nitrogen (BUN) content. Compared to the control group, 6% and 8% M. capsulatus meal diets significantly increased serum total antioxidant capacity (T-AOC) of Jian carp, and 8% M. capsulatus meal diet significantly decreased malondialdehyde (MDA) activity. The study has demonstrated that the replacement of SBM with Methylococcus capsulatus shows promise as an alternative protein source in the aquaculture industry.