Plasma Aspartate Aminotransferase Research Articles

Prolonged Cold Exposure Negatively Impacts Atlantic Salmon (Salmo salar) Liver Metabolism and Function

Large-scale mortality events have occurred during the winter in Atlantic salmon sea cages in Eastern Canada and Iceland. Thus, in salmon held at 3 °C that were apparently healthy (i.e., asymptomatic) and that had ‘early’ and ‘advanced’ symptoms of ‘winter syndrome’/’winter disease’ (WS/WD), we measured hepatic lipid classes and fatty acid levels, and the transcript expression of 34 molecular markers of fatty liver disease (FLD; a clinical sign of WS/WD). In addition, we correlated our results with previously reported characteristics associated with this disease’s progression in these same individuals. Total lipid and triacylglycerol (TAG) levels increased by ~50%, and the expression of 32 of the 34 genes was dysregulated, in fish with symptoms of FLD. TAG was positively correlated with markers of inflammation (5loxa, saa5), hepatosomatic index (HSI), and plasma aspartate aminotransferase levels, but negatively correlated with genes related to lipid metabolism (elovl5b, fabp3a, cd36c), oxidative stress (catc), and growth (igf1). Multivariate analyses clearly showed that the three groups of fish were different, and that saa5 was the largest contributor to differences. Our results provide a number of biomarkers for FLD in salmon, and very strong evidence that prolonged cold exposure can trigger FLD in this ecologically and economically important species.

Efficacy Assessment of Five Policosanol Brands and Damage to Vital Organs in Hyperlipidemic Zebrafish by Six-Week Supplementation: Highlighting the Toxicity of Red Yeast Rice and Safety of Cuban Policosanol (Raydel®).

Policosanol is a mixture of long-chain aliphatic alcohols (LCAAs) derived from various plant and insect origins that are marketed by various companies with distinct formulations and brand names. Policosanols offer several beneficial effects to treat dyslipidemia and hypertension; however, a comprehensive functionality comparison of various policosanol brands has yet to be thoroughly explored. In the present study five distinct policosanol brands from different origins and countries, Raydel-policosanol, Australia (PCO1), Solgar-policosanol, USA (PCO2), NutrioneLife-monacosanol, South Korea (PCO3), Mothernest-policosanol, Australia (PCO4), and Peter & John-policosanol, New Zealand (PCO5) were compared via dietary supplementation (1% in diet, final wt/wt) to zebrafish for six weeks to investigate their impact on survivability, blood lipid profile, and functionality of vital organs under the influence of a high-cholesterol diet (HCD, final 4%, wt/wt). The results revealed that policosanol brands (PCO1-PCO5) had a substantial preventive effect against HCD-induced zebrafish body weight elevation and hyperlipidemia by alleviating total cholesterol (TC) and triglycerides (TG) in blood. Other than PCO3, all the brands significantly reduced the HCD's elevated low-density lipoprotein cholesterol (LDL-C). On the contrary, only PCO1 displayed a significant elevation in high-density lipoprotein cholesterol (HDL-C) level against the consumption of HCD. The divergent effect of PCO1-PCO5 against HCD-induced hepatic damage biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), was observed. PCO1, PCO2, and PCO4 efficiently curtailed the AST and ALT levels; however, PCO3 and PCO5 potentially aggravated the HCD's elevated plasma AST and ALT levels. Consistently, the hepatic histology outcome revealed the least effectiveness of PCO3 and PCO5 against HCD-induced liver damage. On the contrary, PCO1 exhibited a substantial hepatoprotective role by curtailing HCD-induced fatty liver changes, cellular senescent, reactive oxygen species (ROS), and interleukin-6 (IL-6) production. Likewise, the histological outcome from the kidney, testis, and ovary revealed the significant curative effect of PCO1 against the HCD-induced adverse effects. PCO2-PCO5 showed diverse and unequal results, with the least effective being PCO3, followed by PCO5 towards HCD-induced kidney, testis, and ovary damage. The multivariate interpretation based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) validated the superiority of PCO1 over other policosanol brands against the clinical manifestation associated with HCD. Conclusively, different brands displayed distinct impacts against HCD-induced adverse effects, signifying the importance of policosanol formulation and the presence of aliphatic alcohols on the functionality of policosanol products.

Toxic effects of antibiotic oxytetracycline in the fish, Cyprinus carpio using a multi-biomarker approach

Aim: The present study was designed to assess the toxic effect of oxytetracycline in the fish Cyprinus carpio using multi-biomarker approach following acute exposure. Methodology: The fish were exposed to sub-lethal concentration (80 mg l-1) of oxytetracycline for 96 hrs. Blood samples were collected 24, 48, 72 and 96 hrs after treatment. Biomarkers such as genotoxicity, biochemical parameters and alteration of the morphology of scales were used to assess the health status of fish after exposure to oxytetracycline. Genotoxicity was assessed using blood cell micronucleus assay. Results: Significant alterations in the nucleus and cytoplasm were noticed such as the aberrant nucleus and vacuolated cytoplasm which were time dependent in the treatment group compared to the control. Biochemical parameters such as blood glucose, total plasma protein, aspartate transaminase and creatinine levels were significantly altered in the oxytetracycline exposed groups. The examination of body scales of treated fish revealed significant alterations such as uprooted and damaged lepidonts and dispersed chromatophores. Interpretation: The data of the present study indicates that oxytetracycline is toxic to fish at sub-lethal concentration. Key words: Antibiotics, Biomarkers, Cyprinus carpio, Genotoxicity, Oxytetracycline, Scale

Synergistic Anti-Inflammatory Activity of Lipid-Free Apolipoprotein (apo) A-I and CIGB-258 in Acute-Phase Zebrafish via Stabilization of the apoA-I Structure to Enhance Anti-Glycation and Antioxidant Activities.

CIGB-258, a 3 kDa peptide from heat shock protein 60, exhibits synergistic anti-inflammatory activity with apolipoprotein A-I (apoA-I) in reconstituted high-density lipoproteins (rHDLs) via stabilization of the rHDL structure. This study explored the interactions between CIGB-258 and apoA-I in the lipid-free state to assess their synergistic effects in the structural and functional enhancement of apoA-I and HDL. A co-treatment of lipid-free apoA-I and CIGB-258 inhibited the cupric ion-mediated oxidation of low-density lipoprotein (LDL) and a lowering of oxidized species in the dose-responsive manner of CIGB-258. The co-presence of CIGB-258 caused a blue shift in the wavelength of maximum fluorescence (WMF) of apoA-I with protection from proteolytic degradation. The addition of apoA-I:CIGB-258, with a molar ratio of 1:0.1, 1:0.5, and 1:1, to HDL2 and HDL3 remarkably enhanced the antioxidant ability against LDL oxidation up to two-fold higher than HDL alone. HDL-associated paraoxonase activities were elevated up to 28% by the co-addition of apoA-I and CIGB-258, which is linked to the suppression of Cu2+-mediated HDL oxidation with the slowest electromobility. Isothermal denaturation by a urea treatment showed that the co-presence of CIGB-258 attenuated the exposure of intrinsic tryptophan (Trp) and increased the mid-points of denaturation from 2.33 M for apoA-I alone to 2.57 M for an apoA-I:CIGB-258 mixture with a molar ratio of 1:0.5. The addition of CIGB-258 to apoA-I protected the carboxymethyllysine (CML)-facilitated glycation of apoA-I with the prevention of Trp exposure. A co-treatment of apoA-I and CIGB-258 synergistically safeguarded zebrafish embryos from acute death by CML-toxicity, suppressing oxidative stress and apoptosis. In adult zebrafish, the co-treatment of apoA-I+CIGB-258 exerted the highest anti-inflammatory activity with a higher recovery of swimming ability and survivability than apoA-I alone or CIGB-258 alone. A co-injection of apoA-I and CIGB-258 led to the lowest infiltration of neutrophils and interleukin (IL)-6 generation in hepatic tissue, with the lowest serum triglyceride, aspartate transaminase, and alanine transaminase levels in plasma. In conclusion, the co-presence of CIGB-258 ameliorated the beneficial functionalities of apoA-I, such as antioxidant and anti-glycation activities, by enhancing the structural stabilization and protection of apoA-I. The combination of apoA-I and CIGB-258 synergistically enforced the anti-inflammatory effect against CML toxicity in embryos and adult zebrafish.

Phytosterol supplementation enhances the growth performance, feed utilization, antioxidant status and glucose metabolism of juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet

IntroductionPrevious studies found that phytosterols could influence growth performance, feed utilization and lipid metabolism as well as improve the antioxidant capacity of animals.MethodsTo investigate the effects of dietary phytosterol supplementation on juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet, a 56- day feedingtrial was conducted with four dietary feeds for juvenile largemouth bass: extruded floating feed isonitrogenous and isoenergetic diets were formulated to contain 10% and 15% α-starch; on the basis of a 15% α-starch diet, two other diets were formulated with supplementation of 0.1% and 0.5% phytosterol, respectively. After the feeding trials, the survival rate, weight gain and specific growth rate, feed conversion ratio, intraperitoneal fat ratio, feed intake, protein efficiency ratio and activities of three digestive enzymes, as well as the concentrations of nine plasma biochemical indices, hepatic enzyme activities and glycogen contents, were measured and calculated, and the data were statistically analyzed.ResultsThe results of the present study showed that the survival rate, weight gain and specificgrowthrates were significantly greater in plants fed high-starch diets supplemented with phytosterols. As the supplemental phytosterol concentration increased, the feed conversion ratio and intraperitoneal fat ratio significantly decreased; the protease and lipase levels in the pyloric zone markedly increased; the plasma cholesterol, triglyceride, glucose, malondialdehyde, aspartate transaminase and alanin transaminase levels significantly decreased; the glucokinase and pyruvate kinase levelsmarkedly increased; and the hepatic glycogen content significantly decreased.DiscussionIn summary, dietary phytosterol supplementation promoted the growth performance, feed utilization and antioxidant status of juvenile largemouth bass fed a highstarch diet; enhanced glucose utilization and metabolism; and alleviated the negative stimulation of glycemia stress in M. salmoide fed a high-starch diet.

Liraglutide protects against microvascular dysfunction and sepsis-mediated inflammation and organ injury

Introduction: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection characterized by increased systemic inflammation and microvascular injury. Recently, commonly used diabetes and obesity medications, glucagon-like peptide-1 (GLP-1) receptor agonists, have demonstrated unexpected anti-inflammatory effects. We tested GLP-1 receptor agonist liraglutide in a clinically relevant two-hit murine model of polymicrobial abdominal sepsis and hyperoxia and microvascular endothelial injury in vitro, hypothesizing that GLP-1 receptor agonists exert protective effects during sepsis, limiting microvascular permeability, inflammation, organ injury and death. Methods: Sepsis was induced in male and female mice by intraperitoneal (IP) injection of cecal contents (CS;1.8 mg/g body weight) collected from euthanized donor mice. Mice were also exposed to hyperoxia (FiO2 90-96%) for 24 hours. Six and 18 hours after CS injection, mice were administered saline or liraglutide (0.1 mg/kg). At 12 hours, mice were given fluids and antibiotics. At 24 hours, mice were euthanized for plasma and bronchoalveolar lavage (BAL; right lung) collection. Plasma cytokines, organ injury markers, and BAL immune cells and protein were measured. The left lung was tied off and excised to measure wet-to-dry lung weight ratios. Additionally, for in vitro studies, primary human lung microvascular endothelial cells (HLMVECs) were treated with saline or liraglutide for 24 hours prior to saline (control) or LPS (100 ng/mL). HLMVEC barrier dysfunction was quantified using express permeability testing (XPerT) assay or Electric Cell-Substrate Impedance Sensing (ECIS) to measure transendothelial electrical resistance (TER). Results: In murine sepsis, illness severity scores and lung injury were improved in mice pretreated with liraglutide (N=12). Plasma blood urea nitrogen (BUN; P=0.0581), alanine transaminase (ALT; P=0.0311) and aspartate aminotransferase (AST; P=0.0263), and cytokines IL-1β (P=0.0078), IL-6 (P=0.0038), and TNF-α (P=0.0183) in plasma were reduced in mice treated with liraglutide. In HLMVECs, liraglutide (1.5 nM) significantly reduced LPS-induced barrier dysfunction measured by XPerT assay (P=0.0030) and ECIS (P=0.0075). Conclusion: Liraglutide reduces illness severity, inflammation, and organ injury in a two-hit model of sepsis-induced ALI. Liraglutide has direct effects in the microvascular endothelium, limiting LPS-mediated barrier dysfunction. These findings support a protective role for GLP-1 receptor agonism in sepsis, mediated through the microvasculature. HL150783, AG075341, HL158906. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Increased hepatoprotective effects of the novel farnesoid X receptor agonist INT-787 versus obeticholic acid in a mouse model of nonalcoholic steatohepatitis.

The nuclear farnesoid X receptor (FXR), a master regulator of bile acid and metabolic homeostasis, is a key target for treatment of nonalcoholic steatohepatitis (NASH). This study compared efficacy of FXR agonists obeticholic acid (OCA) and INT-787 by liver histopathology, plasma biomarkers of liver damage, and hepatic gene expression profiles in the Amylin liver NASH (AMLN) diet-induced and biopsy-confirmed Lepob/ob mouse model of NASH. Lepob/ob mice were fed the AMLN diet for 12 weeks before liver biopsy and subsequent treatment with vehicle, OCA, or INT-787 for 8 weeks. Hepatic steatosis, inflammation, and fibrosis (liver lipids, galectin-3, and collagen 1a1 [Col1a1], respectively), as well as plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, were assessed. Hepatic gene expression was assessed in Lepob/ob mice that were fed the AMLN diet for 14 weeks then treated with vehicle, OCA, or INT-787 for 2 weeks. INT-787, which is equipotent to OCA but more hydrophilic, significantly reduced liver lipids, galectin-3, and Col1a1 compared with vehicle, and to a greater extent than OCA. INT-787 significantly reduced plasma ALT and AST levels, whereas OCA did not. INT-787 modulated a substantially greater number of genes associated with FXR signaling, lipid metabolism, and stellate cell activation relative to OCA in hepatic tissue. These findings demonstrate greater efficacy of INT-787 treatment compared with OCA in improving liver histopathology, decreasing liver enzyme levels, and enhancing gene regulation, suggesting superior clinical potential of INT-787 for the treatment of NASH and other chronic liver diseases.

EARLY FLUID PLUS NOREPINEPHRINE RESUSCITATION DIMINISHES KIDNEY HYPOPERFUSION AND INFLAMMATION IN SEPTIC NEWBORN PIGS.

Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) sham, 2) sepsis (cecal ligation and puncture) without subsequent resuscitation, and 3) sepsis with lactated Ringer plus norepinephrine resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output and glomerular filtration rate were measured noninvasively. Mean arterial pressure, total renal blood flow, cortical perfusion, medullary perfusion, and medullary tissue oxygen tension (mtPO 2 ) were determined for 12 h. Cecal ligation and puncture decreased mean arterial pressure and cardiac output by more than 50%, with a proportional increase in renal vascular resistance and a 60-80% reduction in renal blood flow, cortical perfusion, medullary perfusion, and mtPO 2 compared to sham. Cecal ligation and puncture also decreased glomerular filtration rate by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO 2 , changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to cecal ligation and puncture develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.

Exploring the effects and possible mechanisms of nutritional selenium nanoparticles on production performance and stress recovery in the Arabian yellowfin seabream (Acanthopagrus arabicus) model

This work examines the impacts of nutritional selenium nanoparticles (SeNPs) on growth, physiological and immunological parameters, antioxidant defense capacity, gene expression, and stress response of fingerling Arabian yellowfin seabream (Acanthopagrus arabicus). SeNPs were added to the basal diet at different dosages of 0 (control), 0.5 (SeNPs-0.5), 1 (SeNPs-1), and 2 (SeNPs-2) mg/Kg diet. The fish with an average weight of 5 ±0.0 g were indiscriminately distributed in 12 tanks (20 fish/ tank) to represent four experimental groups in triplicate that received the diets for 60 days. The results revealed that the SeNPs-1 and SeNPs-2 diets improved growth, feed intake, and feed conversion ratio. Supplemental SeNPs enhanced the expression levels of insulin-like growth factor I, interleukin-1β, and lysozyme genes. Although supplementing SeNPs had no significant effect on superoxide dismutase activity and malondialdehyde concentration, it enhanced the catalase activity in the SeNPs-1 group and the glutathione peroxidase activity in groups supplemented with SeNPs at 0.5 and 1 mg/Kg. The immune parameters improved in fish fed with the SeNPs-1 diet. While SeNPs had no significant impact on plasma total protein, albumin, globulin, alanine aminotransferase, and triglyceride contents in different groups, the SeNPs-1 group had the highest content of plasma high-density lipoprotein and simultaneously the lowest values of cholesterol and low-density lipoprotein. The SeNPs-0.5 and SeNPs-1 diets reduced plasma aspartate aminotransferase content, and the SeNPs-2 diet increased its value. Additionally, SeNPs significantly decreased blood cortisol and lactate levels in fish challenged with acute stress by being confined at the fish density of 200 kg/m3 for 45 min. According to these data, SeNPs at 1 mg/Kg diet is recommended to enhance growth, immunity, and stress resistance in the fish under study.

Piperine attenuates hepatic ischemia/reperfusion injury via suppressing the TLR4 signaling cascade in mice

Piperine, the major active substance in black pepper, has been shown to have anti-inflammatory and antioxidant effects in several ischemic diseases. However, the role of piperine in hepatic ischemia/reperfusion injury (HIRI) and its underlying mechanisms remain unclear. In this study, the mice were administered piperine (30 mg/kg) intragastric administration before surgery. After 24 h of hepatic ischemia-reperfusion, liver histopathological evaluation, serum transaminase measurements, and TUNEL analysis were performed. The infiltration of inflammatory cells and production of inflammatory mediators in the liver tissue were determined by immunofluorescence and immunohistochemical staining. The protein levels of toll-like receptor 4 (TLR4) and related proteins such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-1 receptor-associated kinase 1 (IRAK1), p65, and p38 were detected by western blotting. The results showed that plasma aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte apoptosis, oxidative stress, and inflammatory cell infiltration significantly increased in HIRI mice. Piperine pretreatment notably repaired liver function, improved the histopathology and apoptosis of liver cells, alleviated oxidative stress injury, and reduced inflammatory cell infiltration. Further analysis showed that piperine attenuated tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) production and reduced TLR4 activation and phosphorylation of IRAK1, p38, and NF-κB in HIRI. Piperine has a protective effect against HIRI through the TLR4/IRAK1/NF-κB signaling pathway and may be a safer option for future clinical treatment and prevention of ischemia-related diseases.

Dietary Supplementation of Astragalus membranaceus Extract Affects Growth Performance, Antioxidant Capacity, Immune Response, and Energy Metabolism of Largemouth Bass (Micropterus salmoides).

The present study investigated the effects of Astragalus membranaceus extract (AME) on growth performance, immune response, and energy metabolism of juvenile largemouth bass (Micropterus salmoides). Seven diets containing 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% AME (Con, AME0.1, AME0.2, AME0.3, AME0.4, AME0.5, and AME0.6 groups) were formulated and fed to M. salmoides for 8 weeks. Final body weight (FBW), feed intake (FI), weight gain (WG), and specific growth rate (SGR) were all significantly higher in AME0.4 group than in Con group (P < 0.05). Feed conversion rate (FCR) was significantly improved in AME0.5 group compared with Con group (P < 0.05). Whole-body crude protein contents were significantly increased in AME0.2 group (P < 0.05). Whole-body crude lipid contents were significantly lower in AME0.2 and AME0.3 groups, while muscle lipid was upregulated by dietary AME (P < 0.05). Hepatic malondialdehyde (MDA) contents were significantly lowered in AME0.3 and AME0.4 groups, and catalase (CAT) activities were significantly increased in AME0.1 and AME0.2 groups (P < 0.05). Plasma aspartate aminotransferase (AST) level was significantly lowered in AME0.5, and AME0.6 groups, and alanine aminotransferase (ALT) level was lowered in AME0.5 groups (P < 0.05). Plasma triglyceride was declined in AME0.6 group, and glucose was decreased by 0.3%-0.5% AME (P < 0.05). Significantly higher hepatocyte diameter, lamina propria width, and submucosal layer thickness were recorded in AME0.6 groups, while the longest villi height was obtained in AME0.2 and AME0.3 groups (P < 0.05). The mRNA expression levels of insulin-like growth factor 1 (igf1) revealed the growth-promoting effect of AME. The anti-inflammatory and antiapoptotic effects of AME were demonstrated by transcription levels of interleukin 8 (il-8), tumor necrosis factor-alpha (tnf-a), caspase, B-cell lymphoma-xl (Bcl-xl), bcl-2 associated x (Bax), and bcl-2-associated death protein (Bad). The transcription levels of lipid metabolism and gluconeogenesis related genes, including acetyl-CoA carboxylase alpha (acc1), fatty acid synthase (fasn), fatty acid binding protein 1 (fabp1), phosphoenolpyruvate carboxykinase 2 (pepck2), and glucose-6-phosphatase catalytic subunit 1a (g6pc), were reduced by AME treatment, while the levels of glycolysis-related genes, including glucokinase (gck) and pyruvate kinase (pk), were the highest in AME0.2 and AME0.3 groups (P < 0.05). According to polynomial regression analysis of SGR, WG, FCR, whole-body crude lipid, MDA, and ALT, the optimal AME supplementation level was estimated to be 0.320%-0.429% of the diet. These results provided insights into the roles of AME in regulating immunity and metabolism, which highly indicated its potential as immunostimulants and metabolic regulators in diverse aquatic animals.

Effect of temperature fluctuation on the physiological stress response of hybrid pearl gentian grouper during waterless keeping alive.

Temperature fluctuations are inevitable and have an important impact on the survival of fish during transportation. Therefore, the effect of temperature fluctuation (15 ± 1 °C, 15 ± 2 °C, 15 ± 3 °C) on the muscle quality, physiological, and immune function of hybrid pearl gentian grouper before waterless keeping alive, during keeping alive (0 h, 3 h, 6 h, 9 h, 12 h), and after revival for 12 h was investigated. The plasma glucose concentration of grouper gradually decreased to 0.645 ± 0.007 mg/mL, 0.657 ± 0.006 mg/mL, and 0.677 ± 0.004 mg/mL after keeping alive for 12 h under different temperature fluctuations of 15 ± 1 °C, 15 ± 2 °C, and 15 ± 3 °C, respectively. The cortisol concentration and lysozyme activity of pearl gentian grouper significantly increased (P < 0.05) during the keeping alive period. The results suggested that fish bodies would produce acute stress response, strengthen immune defense ability, and quickly consume a lot of energy to adapt to the low-temperature anhydrous environment. In all treatment groups, the activities of plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) and the content of creatinine gradually increased with the prolongation of the survival time. The hardness and springiness of muscle decreased from 5965.99 ± 20.15 and 0.90 ± 0.00 to 3490.69 ± 27.59 and 0.42 ± 0.01, respectively. In the meanwhile, the change of glycogen and lactic acid content was opposite, indicating that temperature fluctuation harmed the liver, kidney function, and muscle quality. In the later stage of keeping alive, the superoxide dismutase (SOD) and catalase (CAT) activities decreased, especially in the temperature fluctuation group of ±3 °C (125.99 ± 5.48 U/mgprot, 44.21 ± 0.63 U/mgprot), leading to an imbalance of fish immunity. In summary, higher temperature fluctuation would influence the physiological function and immune defense ability and decrease the quality of pearl gentian grouper.

Enhancing Liver Delivery of Gold Nanoclusters via Human Serum Albumin Encapsulation for Autoimmune Hepatitis Alleviation.

Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease caused by the disruption of immune balance, for which effective treatment options are still lacking. In this study, we initially identified glutathione (GSH)-protected AuNCs as a promising nanodrug candidate for AIH alleviating in a Concanavalin A (Con A)-induced mice model. However, to enhance treatment efficiency, liver-targeted delivery needs to be improved. Therefore, human serum albumin (HSA)-encapsulated AuNCs were constructed to achieve enhanced liver targeting and more potent mitigation of Con A-induced elevations in plasma aspartate transaminase (AST), alanine transaminase (ALT), and liver injury in mice. In vivo and in vitro mechanism studies indicated that AuNCs could suppress the secretion of IFN-γ by Con A-stimulated T cells and subsequently inhibit the activation of the JAK2/STAT1 pathway and eventual hepatocyte apoptosis induced by IFN-γ. These actions ultimately protect the liver from immune cell infiltration and damage caused by Con A. These findings suggest that bio-protected AuNCs hold promise as nanodrugs for AIH therapy, with their liver targeting capabilities and therapeutic efficiency being further improved via rational surface ligand engineering.

Variability in residual feed intake, nutrient utilisation and blood parametersin Murrah buffalo calves fed on total mixed ration

The present study was conducted on 18 female Murrah buffalo calves divided into two treatment groups to determine the residual feed intake, nutrient digestibility and blood metabolite parameters when fed with ration containing wheat (Triticum aestivum) straw, berseem (Trifolium alexandrinum) fodder as roughages and concentrate mixture to meet their requirements. Regular recording of body weight and feed intake was done during 90-day trial period. Residual feed intake (RFI) values were determined for individual animals based on which they were divided into low and high RFI groups. DM intake was lower in low RFI animals than high RFI animals. The blood glucose level and growth hormone level in low and high RFI group was comparable in both groups. Low RFI group had greater concentration of creatinine (1.62 vs. 1.21 mg/dL) as well as IGF-1 (136.70 vs. 120.38 ng/mL) whereas, concentration of total plasma protein level (6.80 vs 7.43 g/dL), albumin (3.46 vs 3.71 g/dl), aspartate aminotransferase (102.20 vs. 122.60 IU/L) and cortisol (3.48 vs. 5.32 ng/mL) were lesser in low RFI group with respect to high RFI group, indicating a positive correlation of RFI with total plasma protein, albumin, aspartate aminotransferase and cortisol and a negative correlation with plasma creatinine and IGF-1 levels in female Murrah buffalo calves. It was concluded that low RFI group of female Murrah buffalo calves showed better performance when fed with total mixed ration.

Assessment of Liver Toxicity in Wistar Rats after Chronic Exposure to Phosphate-Processing Wastewaters from Gafsa-Metlaoui Laundry in Tunisia

In the mining basin of the Gafsa region in southwestern Tunisia, environmental exposure to randomly discharged phosphate-processing wastewaters (PPWW) presents a serious threat to health and the surrounding ecosystems. Thus, the contaminated areas are in continuous deterioration over time. There is a paucity of information on the deleterious effects of this kind of effluent. In the current work, the PPWW characterization showed the presence of high contents of Pb (0.90 ± 0.02 mg/L), Cd (0.35 ± 0.27 mg/L), Cr (0.43 ± 0.1 mg/L) and Fe (215.1 ± 2.41 mg/L), exceeding the permissible limits. To assess the chronic toxicity of the effluent in mammalians, two doses of PPWW (50% and 100%) were administered by gavage to Wistar rats for 28 consecutive days. The results revealed that the two PPWW concentrations significantly increased the plasma biochemical markers (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)), compared to untreated animals. Moreover, PPWW treatment severely altered the lipid profile by increasing the contents of triglycerides, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-cholesterol) by 143%, 114%, and 91%, respectively, and significantly reduced the high-density lipoprotein cholesterol (HDL-cholesterol) level by 46%, compared to the control animals. In addition to the significant decrease in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the liver of intoxicated rats, the malondialdehyde (MDA) level was remarkably altered. All of these were associated with deep histopathological damages, materialized by dilatation of sinusoids, congestion of the centrilobular vein, and inflammatory cell infiltration. These disturbances were accompanied by metal detection in the liver and blood. Additionally, DNA fragmentation detected in hepatic tissues highlighted the genotoxic effects of PPWW. All of the aforementioned effects occurred in a PPWW dose-dependent manner. These findings evidenced, for the first time, the in vivo-deleterious impacts of this type of effluent on mammalians inhabiting the mining basin area and therefore showed the real threats to which humans, as consumers, could be exposed. Accordingly, there is a dire need to pay special attention to PPWW before being discharged into environmental ecosystems without any prior treatments.

Effects of Myrcene Addition to Water on Plasma Biochemical Characteristics of Common Carp, Cyprinus carpio, During Transportation

Background: Sedative agents are utilized to mitigate stress and improve fish welfare during and after transportation. Objectives: We aimed to assess the effects of myrcene addition to the transportation water on the plasma biochemical profile of common carp, Cyprinus carpio. Methods: For this purpose, common carp (mean weight of 45.3±1.65 g) were transported in plastic bags containing myrcene at concentrations of 0 (CTL), 10 (10 M), 20 (20 M), 30 (30 M), and 50 (50 M) µL/L for 6 h. Then, their plasma parameters were compared to those values before transportation (BT). Results: Transportation significantly (P&lt;0.05) decreased plasma total protein, albumin, alternative complement, lysozyme, sodium, and chloride, while increasing potassium, calcium, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the CTL treatment, as compared to BT. Adding 50 µL/L myrcene to water prevented total plasma protein and albumin loss. Supplementing 20 µL/L myrcene to water prevented or reduced the changes in plasma ions, alanine aminotransferase, and alkaline phosphatase. Addition of 10-50 µL/L myrcene to water decreased the changes in plasma aspartate aminotransferase. Adding 20 and 30 µL/L myrcene to water mitigated the changes in plasma alternative complement, as 30 µL/L myrcene increased plasma lysozyme activity. Transportation and myrcene addition had no significant effects on plasma immunoglobulin (P&gt;0.05). However, a significant increase was observed in plasma globulin in the 20 M treatment (P&lt;0.05). Conclusion: In summary, adding 20 µL/L myrcene to the transport water of common carp reduced hepatic enzyme levels and improved immune parameters, and therefore, the use of myrcene improves fish welfare during transportation.

Pseudo-targeted metabolomics study of immune stress-mediated idiosyncratic liver injury induced by synergistic effects of bavachin and epimedin B

Chinese patent medicine preparations containing Epimedii Folium and Psoraleae Fructus have been associated with the occurrence of idiosyncratic drug-induced liver injury(IDILI). However, the specific toxic biomarkers and mechanisms underlying these effects remain unclear. This study aimed to comprehensively assess the impact of bavachin and epimedin B, two principal consti-tuents found in Psoraleae Fructus and Epimedii Folium, on an IDILI model induced by tumor necrosis factor-α(TNF-α) treatment, both in vitro and in vivo. To evaluate the extent of liver injury, various parameters were assessed. Lactate dehydrogenase(LDH) release in the cell culture supernatant, as well as the levels of alanine aminotransferase(ALT) and aspartate transaminase(AST) in mouse plasma were measured. Additionally, histological analysis employing hematoxylin-eosin staining was performed to observe liver tissue changes indicative of the severity of liver injury. Furthermore, a pseudo-targeted metabolomics approach was employed, followed by multivariate analysis, to identify differential metabolites. These identified metabolites were subsequently subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The results showed that at the cellular level, after 2 hours of TNF-α stimulation, bavachin significantly increased the release of LDH in HepG2 cells compared to the normal group and the group treated alone; after the combination of bavachin and epimedin B, the release of LDH further significantly increased on the original basis. Similarly, although the individual or combination treatments of bavachin and epimedin B did not induce liver injury in normal mice, the combination of both drugs induced marked liver injury in TNF-α treated mice, leading to a significant elevation in plasma AST and ALT levels and substantial infiltration of inflammatory immune cells in the liver tissue. Pseudo-targeted metabolomics analysis identified seven common differential metabolites. Among these, D-glucosamine-6-phosphate, N1-methyl-2-pyridone-5-carboxamide, 17beta-nitro-5a-androstane, irisolidone-7-O-glucuronide, and N-(1-deoxy-1-fructosyl) valine emerged as potential biomarkers, with an area under the curve(AUC) exceeding 0.9. Furthermore, our results suggest that the metabolism of nicotinic acid and nicotinamide, as well as the linoleic acid metabolic pathway, may play pivotal roles in bavachin and epimedin B-induced IDILI. In conclusion, within an immune-stressed environment mediated by TNF-α, bavachin and epimedin B appear to induce IDILI through disruptions in metabolic processes.

Ecotoxicological Assessment of Ponds Contaminated by Wastewater of Livestock Enterprises by Fish Biomarkers

The morphometric characteristics of internal organs, the morphological composition of blood, and indicators of metabolic processes in the blood plasma and hepatopancreas of the two-year-old carp (&lt;i&gt;Cyprinus carpio&lt;/i&gt; L.) from the conditionally clean pond and contaminated with sewage from a livestock enterprise pond were examined. It was established that the considered contamination caused increase of the spleen mass and its index respectively 1.63 and 1.65 times, but did not affect live weight, body length and height, body structure index, hepatopancreas mass and its index. The hemoglobin concentration, number of erythrocytes, thrombocytes and monocytes in blood of carps from the contaminated pond was lower than in control, whereas number of the segmented neutrophils and ESR were higher, and the number of leukocytes, eosinophils, lymphocytes and rod-nucleated neutrophils did not differ. Wastewater from the livestock enterprise affected metabolic processes in carp, particularly caused increase of the glucose and total protein concentration, the lactate dehydrogenase, aspartate aminotransferase and creatine kinase activity in blood plasma and hepatopancreas. At the same time, there were no differences between specimens from the conditionally clean and contaminated pond in terms of content of triglycerols, cholesterol, urea, creatinine, calcium, inorganic phosphorus, AlAT and AsAt activity in blood plasma and hepatopancreas and total protein content and LHD activity in hepatopancreas, content of total protein, glucose, creatinine, urea, the glucose content in hepatopancreas. The established changes in internal organs, morphological composition of blood and metabolic parameters, particularly concentration of hemoglobin and the erythrocytes number in blood, glucose and total protein content, and activity of lactate dehydrogenase and creatine kinase in carp enabled to propose to use these parameters as supplementary over assessment of the ecotoxicological state of ponds contaminated by wastewater from livestock enterprises.

A Study of the Relationship Between the Triglyceride-Glucose Index and Skeletal Muscle Mass in a General Chinese Population.

There is no study on the relationship between triglyceride-glucose index (TyG index) and skeletal muscle mass in middle-aged and elderly C population. Therefore, the aim of the study is to investigate the relationship between the TyG index and weight-adjusted relative skeletal muscle index (RSMI) in middle-aged and elderly C population. We retrospectively studied 947 aged ⩾40 years subjects who got a routine medical examination in the Department of Geriatrics of R Hospital from May 2021 to March 2023. The RSMI was designed to evaluate skeletal muscle mass and calculated based on lean mass of the limbs(kg)/body weight(kg) × 100%. Skeletal muscle mass reduction was defined as a RSMI of 1-2 standard deviations (SD) below of healthy adults aged 30-49 years old. Considering the quartile groups of the TyG index, the subjects were assigned to 4 groups: Q1 (less than or equal to 8.171), Q2 (from 8.172 to 8.569), Q3 (from 8.570 to 8.992), and Q4 (greater than or equal to 8.993). With TyG index increased, RSMI levels significantly reduced(P < .001). Spearman's correlation analysis showed that the TyG index was negatively correlated with RSMI in males (r = -0.320) and females (r = -0.240). The TyG index was positively correlated with body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (P < .05). Besides, binary logistic regression analysis showed that the risk of developing reduced skeletal muscle mass in the group Q4 was 2.131 (95%CI:1.118-4.064) in males; and was 2.472 (95%CI:1.581-3.867) in females compared to the Q1 group. TyG index was negatively correlated with relative skeletal muscle index, and a higher TyG index was associated with the development of reduced skeletal muscle mass independently of other influencing factors. Therefore, the TyG index promises to be a predictor of skeletal muscle mass loss.

Time-restricted feeding has a limited effect on hepatic lipid accumulation, inflammation and fibrosis in a choline-deficient high-fat diet-induced murine NASH model.

Nonalcoholic steatohepatitis (NASH) occurs worldwide and is characterized by lipid accumulation in hepatocytes, hepatic inflammation, fibrosis, and an increased risk of cirrhosis. Although a major proportion of NASH patients exhibit obesity and insulin resistance, 20% lack a high body mass and are categorized as "non-obese NASH". Time-restricted feeding (TRF), limiting daily food intake within certain hours, improves obesity, lipid metabolism, and liver inflammation. Here, we determined whether TRF affects NASH pathology induced by a choline-deficient high-fat diet (CDAHFD), which does not involve obesity. TRF ameliorated the increase in epididymal white adipose tissue and plasma alanine transaminase and aspartate transaminase levels after 8 weeks of a CDAHFD. Although gene expression of TNF alpha in the liver was suppressed by TRF, it did not exhibit a suppressive effect on hepatic lipid accumulation, gene expression of cytokines and macrophage markers (Mcp1, IL1b, F4/80), or fibrosis, as evaluated by Sirius red staining and western blot analysis of alpha-smooth muscle actin. A CDAHFD-induced increase in gene expression related to fibrogenesis (Collagen 1a1 and TGFβ) was neither suppressed by TRF nor that of alpha-smooth muscle actin but was increased by TRF. Our results indicated that TRF has a limited suppressive effect on CDAHFD-induced NASH pathology.