Plasma Aspartate Aminotransferase Research Articles

Effect of Butaphosphan and Cyanocobalamin on the Metabolic Profile, Oxidative Stress and Prophylaxis of Ovine Pregnancy Toxemia.

The study was conducted to evaluate the effect of butaphosphan and cyanocobalamin (BC) on the metabolic profile, oxidative stress in Kashmiri merino ewes and its effect on the prophylaxis of Ovine pregnancy toxemia (PT). A total of 48 ewes were randomly divided into three groups, each consisting of 16 ewes. High dose BC (HBC): Ewes were given 0.2 mL BC/kg body weight, subcutaneously (SC) weekly from 6 weeks pre-lambing to lambing. Low dose BC (LBC): Ewes were given 0.1 mL BC/kg body weight, SC weekly from 6 weeks pre-lambing to lambing. No BC (CON): Ewes were given 0.2 mL normal saline/kg body weight, SC. Weekly from six pre-lambing to lambing. A significant effect of treatment was observed on non-esterified fatty acid (NEFA; p = 0.06), beta hydroxybutyric acid (β-HBA, p = 0.008), fructosamine (p = 0.034) and oxidative stress indices (OSI; p = 0.026) with less NEFA, β-HBA, OSI and more fructosamine levels in HBC followed by LBC. The BC did not affect glucose, cholesterol, blood urea nitrogen, creatinine, total antioxidant capacity, calcium and phosphorus however a significant difference was observed along the sampling time in all the three groups. Plasma triglyceride, aspartate aminotransferase and total oxidant status levels showed a significant treatment-time interaction. Taking 0.8 mmol/L β-HBA as the cutoff limit for subclinical PT, only HBC was able to significantly control PT at 3 weeks pre-lambing (OR; 5.57; p = 0.035), at 2 weeks pre-lambing (OR: 9.53; p = 0.007), at 1-week pre-lambing (OR: 6.60; p = 0.017) and at lambing (OR: 5.57; p = 0.035). In conclusion, there was a positive effect of BC treatment on the energy metabolism in pregnant ewes and it helped in the amelioration of oxidative stress and hence can be used in the prophylaxis of PT.

Chemical profiling, in-silico investigation and in vivo toxicity assessment of lacatomtom (a psychoactive mixture) on selected indices in albino wistar rats

aims: To evaluate the safety and identify the psychoactive constituent of a new psychoactive cocktail that is abused among African youths. background: The use of lacatomtom (LTT), a psychoactive mixture of tomtom (TT) candies with lacasera (LC) beverage, has recently increased among young Nigerians and Africans. There isn't much scientific study on the constituent and effects of this psychoactive substance. objective: To chemically-profile the mixture using GCMS analysis, and evaluate the effect of the constituent of neural targets. To evaluate the toxicological effects in albino rats. To identify neur method: Herein, LTT was chemically-profiled using GCMS analysis, and the toxicological effects were examined in albino rats. In vivo experiment consists of five groups of six rats each (group 2 - LTT ad libitum; groups 1, 3, & 4 - TTT, TT, LC (1 mL) mg/mL kg/body weight once/day respectively, group 5 - distilled water ad libitum). Identified constituents were examined against human monoamine oxidase (hMOA) and human catechol O-methyltransferase (hCOMT) using in silico methods. result: Forty-seven chemical compounds were identified. Ad libitum intake of LTT elevated plasma alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, total cholesterol, and LDL-cholesterol levels. The docked poses, binding scores, and interactions with amino acids informed the selection of (4-Methoxymethoxy-hex-5-ynylidene)-cyclohexane (MM) (-9.4 kcal/mol) and 3-(hydroxyphenylmethyl)-3,4-dimethyl-1-phenylpentan-2-one (HP) for hCOMT (-9.4 kcal/mol), while propionylcodeine (-10.1 kcal/mol) and HP (-8.9 kcal/mol) for hMOA. Top-docked compounds (TDC) demonstrated the potential to permeate the blood-brain barrier. TDC was predicted to be a positive substrate of the P-glycoprotein and presents inhibitory potential for cytochrome P450 descriptors. HP was mutagenic and could induce human hepatotoxicity and drug-induced liver injury, while propionylcodeine had human hepatotoxic prediction. conclusion: The present study, for the first time, confirmed the potential toxicity of lacatomtom to the liver, kidney, heart, and central nervous system supported by the identified top-docked compounds regarded as potential psychoactive constituents of hMOA and hCOMT. other: Nono

Effects of Replacing Fish Meal with Rubber Seed Cake on Growth, Digestive, Antioxidant and Protein Metabolism of Juvenile Asian Red-Tailed Catfish (Hemibagrus wyckioides).

An 8-week feeding trial was conducted to assess the impact of replacing fish meal (FM) with rubber seed cake (RSC) on growth performance, digestive enzyme activity of the gut, antioxidant capacity and protein metabolism-related parameters of plasma and liver in juvenile Asian red-tailed catfish (Hemibagrus wyckioides) with an average body weight of 3.21 g. Four isonitrogenous (41.08 ± 0.17) and isolipidic (10.07 ± 0.11) diets were formulated, incorporating RSC at a level of 0%, 15%, 30%, and 45% (w/w) to progressively replace FM. Dietary inclusion of 15-30% RSC did not significantly affect growth performance (p > 0.05). However, the replacement of FM with RSC resulted in linear reductions in intestinal trypsin and amylase activities, with a significant reduction in intestinal amylase activity observed at the 45% RSC inclusion level. Dietary inclusion of 30-45% RSC decreased plasma glutamate dehydrogenase and aspartate aminotransferase activities, but increased plasma adenosine monophosphate deaminase and hepatic γ-glutamyltransferase activities. This may indicate that the high substitution of FM by RSC may affect the homeostasis of amino acid metabolism. Dietary inclusion of 15% RSC did not affect serum and hepatic antioxidant enzyme activities; however, dietary inclusion of 45% RSC significantly increased plasma malondialdehyde level, but decreased catalase activity. Furthermore, dietary inclusion of 30-45% RSC significantly increased hepatic lactate dehydrogenase activity. These results demonstrated that replacing a portion of FM with RSC is feasible, and dietary inclusion of 15% RSC did not have significant adverse effects on growth performance, digestive function and antioxidant capacity of H. wyckioides.

Comparative Assessment of Beeswax Alcohol and Coenzyme Q10 (CoQ10) to Prevent Liver Aging, Organ Damage, and Oxidative Stress in Hyperlipidemic Zebrafish Exposed to D-Galactose: A 12-Week Dietary Intervention.

The current study was designed to compare in vivo efficacy between beeswax alcohol (BWA) and coenzyme Q10 (CoQ10) to treat fatty liver changes, oxidative stress, and damages in major organs of zebrafish by 12 weeks with high-cholesterol (HC) and galactose (Gal) supplementation. At week 12, the HC control and HC+Gal control groups showed 96% and 92% survivability, respectively, while co-supplementation of the 0.5% BWA and 1.0% BWA groups exhibited 96% and 100% survivability. However, co-supplementation of the 0.5% CoQ10 and 1.0% CoQ10 groups revealed the lowest survivability, around 92% and 89%, respectively. The 0.5% BWA and 1.0% BWA groups showed 21% (p < 0.001) and 41% (p < 0.001), respectively, lower total cholesterol (TC) than the HC+Gal control, while the 1.0% CoQ10 group showed only 15% lower TC than the control. Interestingly, the 0.5% BWA and 1.0% BWA groups showed 22% (p < 0.001) and 38% (p < 0.001), respectively, lower triglyceride (TG) than the HC+Gal control. However, both the 0.5% CoQ10 and 1.0% CoQ10 groups showed similar TG levels as the control, suggesting that CoQ10 supplementation had no effect on lowering serum TG. The 1.0% BWA group showed the highest plasma HDL-C and HDL-C/TC (%) up to 3.2-fold and 5.5-fold, respectively, higher than those of the HC+Gal control, while the 1.0% CoQ10 group showed 2.4-fold and 2.8-fold higher plasma HDL-C and HDL-C/TC (%), respectively, than the control. The plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels were lowest in the 1.0% BWA group, 51% and 72%, respectively, lower than HC+Gal control, suggesting the lowest extent of hepatic damage. In hepatic tissue, neutrophil infiltration and interleukin (IL)-6 production were the lowest in the 1.0% BWA group, around 67% and 85%, respectively, lower than the HC+Gal control. Fatty liver change, cellular apoptosis, and cell senescence in hepatic tissue were remarkably lowered in the 1.0% BWA group, while the CoQ10 group showed much less effect than the BWA group. In kidney, ovary, and testis tissue, the 1.0% BWA group showed the lowest production of reactive oxygen species, the extent of cellular senescence, and cellular apoptosis with the healthiest cell morphology. In conclusion, supplementation of BWA remarkably protected the liver, kidney, ovary, and testis from oxidative damage by cholesterol and galactose consumption, with the least serum AST and ALT levels, inflammatory parameters, and senescence markers.

Novel Peripherally Selective Cannabinoid Receptor 1 Neutral Antagonist Improves Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally. MASLD is characterized by clinically significant liver steatosis, and a subset of patients progress to more severe metabolic-disorder-associated steatohepatitis (MASH) with liver inflammation and fibrosis. Cannabinoid receptor 1 (CB1) antagonism is a proven therapeutic strategy for the treatment of the phenotypes that underlie MASLD, though work on early centrally penetrant compounds largely ceased following adverse psychiatric indications in humans. We present here preclinical testing of a CB1 neutral antagonist, N-[1-[8-(2-Chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]-4-phenylpiperidin-4l]methanesulfonamide (RTI-348), with minimal brain exposure when administered to mice. In a diet-induced model of MASLD-induced MASH, administration of RTI-348 decreased the total body and liver weight gain. Animals treated with RTI-348 showed reduced steatosis. Furthermore, they produced lower plasma alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), biomarkers associated with liver damage. Mice maintained on the MASH diet had elevated expression of genes associated with profibrogenesis, immune response, and extracellular matrix remodeling, and treatment with RTI-348 mitigated these diet-induced changes in gene expression. Using an intracranial electrical self-stimulation model, we also demonstrated that RTI-348 does not produce an anhedonia response, as seen with the first-generation CB1 inverse agonist rimonabant. Altogether, the results herein point to RTI-348 as a promising neutral antagonist for MASH.

Suppressive Effects of β-Hydroxybutyrate Administration on Lipopolysaccharide-Induced Inflammation in Broiler Chickens.

This study aimed to evaluate the suppressive effects of β-hydroxybutyrate (BHB) administration on lipopolysaccharide (LPS)-induced inflammation in broiler chickens. Twenty-day-old male broiler chickens were randomly allocated to three groups, each of which was treated with saline (control), intraperitoneal administration of LPS [1.5 mg/kg body weight (BW), Escherichia coli O127:B8], or LPS plus BHB (3 mmol/kg BW). Plasma albumin and total protein concentration were significantly reduced by LPS administration, while BHB co-treatment partially attenuated the effects. The LPS treatment significantly induced plasma aspartate and alanine aminotransferase activities, and interleukin (IL)-6 concentration, with the increases suppressed by BHB co-treatment (p < 0.05). The LPS treatment significantly increased the gene expression levels of IL-1β, IL-6, and IL-18 in the spleen and peripheral blood monocytes (PBMC), while the increases were partially attenuated by BHB in the spleen. Relatively higher levels of BHB dehydrogenase 1 and succinyl-CoA:3-ketoacid CoA transferase were observed in the spleen and skeletal muscle, while these gene levels were lower in PBMC and the liver. The present results suggest that BHB can suppress LPS-induced inflammation, in which ketolytic enzyme expression levels may be involved in broiler chickens.

The potential role of exopolysaccharide from Graesiella sp (chlorophyte Microalga) as dietary supplement against Bisphenol A-induced hepatotoxicity in gilthead sea bream (Sparus aurata)

ABSTRACT Bioactive compounds derived from microalgae exhibit beneficial biological activities for human and animal health. The present study was conducted to assess the potential protective effect of exopolysaccharide EPSs extracted from Graesiella sp, against Bisphenol-A toxicity in gilthead sea bream (Sparus aurata). Fish were divided into two groups, the first group was fed a basal diet without EPSs and the second one was fed a supplemented diet (1.5% of EPSs) for 55 days. Subsequently, a random sample from each group were intraperitoneally injected with Bisphenol A (BPA) at a concentration of 50 mg/kg body weight. The antioxidant status, plasma biochemistry, tissue histopathology and flesh quality were then assessed after five days of BPA injection. Our results show that EPSs supplementation didn't induce negative effects for all tested parameters. BPA exposure caused a significant increment of hepatic lipid peroxidation and drops by more than 50% in the catalase (CAT), isocitrate dehydrogenase (ICDH) and reduced glutathione (GSH) activities. BPA induced also a significant increase in plasma aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activities and numerous hepatic alterations. Interestingly, the BPA damage was reduced in fish fed with EPS-enriched diets suggesting that Graesiella-EPS can be supplemented to prevent BPA damage.

P3]PP, a stable, long-acting pancreatic polypeptide analogue, evokes weight lowering and pancreatic beta-cell-protective effects in obesity-associated diabetes.

To thoroughly investigate the impact of sustained neuropeptide Y4 receptor (NPY4R) activation in obesity-associated diabetes. Initially, the prolonged pharmacodynamic profile of the enzymatically stable pancreatic polypeptide (PP) analogue, [P3]PP, was confirmed in normal mice up to 24 h after injection. Subsequent to this, [P3]PP was administered twice daily (25 nmol/kg) for 28 days to high-fat-fed mice with streptozotocin-induced insulin deficiency, known as HFF/STZ mice. Treatment with [P3]PP for 28 days reduced energy intake and was associated with notable weight loss. In addition, circulating glucose was returned to values of approximately 8 mmol/L in [P3]PP-treated mice, with significantly increased plasma insulin and decreased glucagon concentrations. Glucose tolerance and glucose-stimulated insulin secretion were improved in [P3]PP-treated HFF/STZ mice, with no obvious effect on peripheral insulin sensitivity. Benefits on insulin secretion were associated with elevated pancreatic insulin content as well as islet and beta-cell areas. Positive effects on islet architecture were linked to increased beta-cell proliferation and decreased apoptosis. Treatment intervention also decreased islet alpha-cell area, but pancreatic glucagon content remained unaffected. In addition, [P3]PP-treated HFF/STZ mice presented with reduced plasma alanine transaminase and aspartate transaminase levels, with no change in circulating amylase concentrations. In terms of plasma lipid profile, triglyceride and cholesterol levels were significantly decreased by [P3]PP treatment, when compared to saline controls. Collectively, these data highlight for the first time the potential of enzymatically stable PP analogues for the treatment of obesity and related diabetes.

Aloperine Attenuates Hepatic Ischemia/Reperfusion-Induced Liver Injury via STAT-3 Signaling in a Murine Model.

Hepatic ischemia/reperfusion (I/R) damage is one of the most common side effects of liver surgery. This pathophysiological process may lead to excessive hepatic damage. Aloperine is an active ingredient isolated from Sophora alopecuroides Linn and has a variety of therapeutic effects, including organ protection. However, the hepatoprotective effect of aloperine against hepatic I/R damage has not yet been determined. C57BL/6 mice were allocated to the sham-operated (sham), hepatic ischemia/reperfusion (I/R), and aloperine groups. The mice were exposed to 30 min of hepatic hilum occlusion. Then a 3-h reperfusion was performed. Mice in the sham group underwent sham surgery. Hepatic injury was evaluated by plasma aspartate aminotransferase (AST) and transaminase alanine aminotransferase (ALT) levels, histological evaluation, cell apoptosis, the number of activated inflammatory cells, and the expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. The protein phosphorylation status of the reperfusion-associated survival pathways was evaluated. Mice with hepatic I/R injury presented increased plasma ALT and AST levels, increased hepatic apoptosis, abnormal histological structure, and elevated inflammatory responses. However, aloperine ameliorated hepatic I/R-induced injury. Moreover, aloperine enhanced the level of signal transducer and activator of transcription (STAT)-3 phosphorylation after I/R. Ag490, an agent that inhibits STAT-3 activity, abolished aloperine-induced STAT-3 phosphorylation and liver protection. Aloperine ameliorates hepatic I/R-induced liver injury via a STAT-3-mediated protective mechanism. Patients with hepatic I/R injury may benefit from aloperine treatment. SIGNIFICANCE STATEMENT: Hepatic I/R can cause excessive liver damage. This study revealed that aloperine, an active component isolated from Sophora alopecuroides Linn, ameliorates hepatic I/R injury and related liver damage in vivo. The underlying protective mechanism may involve the STAT-3 signaling pathway. These findings may lead to the development of a novel approach for treating hepatic I/R damage in clinical practice.

Diacylglycerol O-acyltransferase 1 inhibitor increases plasma alanine aminotransferase and aspartate aminotransferase activities via a shedding of the intestinal villi and an increase in intestinal permeability in rats

Diacylglycerol O-acyltransferase 1 (DGAT1) is a key enzyme for fat absorption step in the enterocytes. We previously reported that DGAT1 inhibition increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in corn oil-loaded rats via protein kinase C (PKC) activation. In the present study, we investigated the mechanism with respect to the morphology and permeability of the small intestine, focusing on PKC function, and found that shortening of the intestinal villi and a decrease in the number of tdT-mediated dUTP-biotin nick-end labeling-positive cells in the tips of the villi were observed in the jejunum of DGAT1 inhibitor-treated rats loaded with corn oil. These results suggested that the tips of the villi were shed into the intestinal lumen. Next, fluorescein isothiocyanate-dextran, 110 kDa (FD-110) was administered intraduodenally to DGAT1 inhibitor-treated rats loaded with corn oil and we found that plasma FD-110 concentrations increased, indicating that the intestinal permeability to molecules with a molecular weight of approximately 110,000 (e.g., ALT and AST) increased. Taken together, the present results suggested that DGAT1 inhibitor-treatment in combination with corn oil causes ALT and AST to leak from the enterocytes into the blood by shedding the tips of the intestinal villi and increasing intestinal permeability.

Rutaecarpine Aggravates Acetaminophen-Induced Acute Liver Injury by Inducing CYP1A2.

In this study, we investigated whether rutaecarpine could aggravate acetaminophen-induced acute liver damage in vivo and in vitro. CCK-8 and apoptosis assays were performed to verify the cytotoxicity of acetaminophen to L02 cells with or without rutaecarpine. The expression levels of the target proteins and genes were determined using Western blotting and qRT-PCR. The liver pathological changes were evaluated with hematoxylin and eosin staining, while the aspartate aminotransferase (AST) and alanine aminotransferase (AST) levels in plasma were measured to assess the liver damage. Our results revealed that pretreatment of the cell and mice with rutaecarpine significantly aggravated the acetaminophen-induced liver damage. Mechanistically, rutaecarpine induces the CYP1A2 protein, which accelerates the metabolism of acetaminophen to produce a toxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI), leading to severe liver inflammation. Rutaecarpine exacerbated the liver damage by upregulating CYP1A2 and proinflammatory factors. These findings highlight the importance of carefully considering the dosage of rutaecarpine when combined with acetaminophen in drug design and preclinical trials.

Enhancing Liver Transplant Outcomes through Liver Precooling to Mitigate Inflammatory Response and Protect Mitochondrial Function.

Transplanted organs experience several episodes of ischemia and ischemia-reperfusion. The graft injury resulting from ischemia-reperfusion (IRI) remains a significant obstacle to the successful survival of transplanted grafts. Temperature significantly influences cellular metabolic rates because biochemical reactions are highly sensitive to temperature changes. Consequently, lowering the temperature could reduce the degradative reactions triggered by ischemia. In mitigating IRI in liver grafts, the potential protective effect of localized hypothermia on the liver prior to blood flow obstruction has yet to be explored. In this study, we applied local hypothermia to mouse donor livers for a specific duration before stopping blood flow to liver lobes, a procedure called "liver precooling". Mouse donor liver temperature in control groups was controlled at 37 °C. Subsequently, the liver donors were preserved in cold University of Wisconsin solution for various durations followed by orthotopic liver transplantation. Liver graft injury, function and inflammation were assessed at 1 and 2 days post-transplantation. Liver precooling exhibited a significant improvement in graft function, revealing more than a 47% decrease in plasma aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, coupled with a remarkable reduction of approximately 50% in liver graft histological damage compared to the control group. The protective effects of liver precooling were associated with the preservation of mitochondrial function, a substantial reduction in hepatocyte cell death, and a significantly attenuated inflammatory response. Taken together, reducing the cellular metabolism and enzymatic activity to a minimum level before ischemia protects against IRI during transplantation.

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.

ИЗМЕНЕНИЯ БИОХИМИЧЕСКИХ ПОКАЗАТЕЛЕЙ КРОВИ У КРЫС ЛИНИИ WISTAR ПОСЛЕ ИМПЛАНТАЦИИ ФРАГМЕНТОВ СОСУДИСТЫХ ПРОТЕЗОВ

Background. This article deals with the use of biological vascular grafts made from bovine xenopericardium as a plastic material for reconstructive operations on the great vessels, which is one of the most important topics in modern vascular surgery. Aim. To compare changes in blood biochemical parameters in Wistar rats after implantation of fragments of biological and synthetic vascular grafts. Material and methods. The experimental study was performed on male laboratory Wistar rats (n = 50). The animals were divided into two groups: group 1 included 25 animals with implantation of a Dacron vascular graft; group 2 was composed of 25 animals with implantation of a vascular graft made from bovine xenopericardium. Blood samples from the laboratory rats were collected on days 3, 7, 14, 21 and 30 after the operation. Plasma urea, creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase levels were measured. Results. No clinically significant changes in concentrations of low molecular weight metabolites of nitrogen metabolism or liver enzymes activity, alkaline phosphatase and lactate dehydrogenase activity were observed after implantation of a biological vascular graft from bovine xenopericardium compared to the animals with implanted synthetic vascular graft. Conclusion. The use of a biological vascular graft made from bovine xenopericardium does not cause clinically significant changes in blood biochemical parameters in laboratory rats.

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.

COMBINED EFFECT OF ETHYLTHIOSULFАNYLATE AND VITAMIN E ON THE ENZYMATIC ACTIVITY OF AMINOTRANSFERASES IN RAT BLOOD PLASMA UNDER THE TOXIC EFFECT OF Cr(VI)

Aim. The aim of our study was to investigate the effect of ethylthiosulfаnylate (ETS) and vitamin E on the enzymatic activity of blood plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of rats exposed to Cr(VI). Methods. The study was performed on male Wistar rats divided into 6 groups of 5 animals each. The animals were administrated with: group I (control) – physiological saline for 7 days; group III – 2.5 mg Cr(VI)/kg b.w. for 14 days; group II – oil for 14 days; group IV – vitamin E oil solution [20 mg/kg b.w.] for 14 days; group V – ETS oil solution [100 mg/kg b.w.] and vitamin E [20 mg/kg b.w.] for 14 days; group VI – ETS oil solution [100 mg/kg b.w.] and vitamin E [20 mg/kg b.w.] for 14 days, after which 2.5 mg Cr(VI)/kg b.w. for 14 days. We determined the activity of AST, ALT and de Ritis coefficient in blood plasma. Results: The activity of AST, ALT significantly increased (by 40%, 122%) and de Ritis coefficient significantly decreased (by 37%) in the blood plasma of rats after 14 days of Cr(VI) toxicity. AST, ALT increased (by 24%, 61%) also after combined exposure to ETS and vitamin E by subsequent 14-day exposure to Cr(VI) in the blood plasma of rats. Conclusion: Cr(VI)-induced stimulation of blood plasma AST and ALT was twofold lower after combined pretreatment with ETS and vitamin E.