Liver Lactate Dehydrogenase Research Articles

Reduction of hyperglycemia in STZ-induced diabetic mice by prophylactic treatment with heat-killed Mycobacterium aurum: possible effects on glucose utilization, mitochondrial uncoupling, and oxidative stress in liver and skeletal muscle.

In addition to conventional treatment and modifications in physical activity and diet, alternative strategies have been investigated to manage, prevent, or delay diabetes in humans. In this regard, one strategy has relied on the immunomodulatory properties of mycobacteria, whereby Bacillus Calmette-Guerin, an attenuated live strain of Mycobacterium bovis, has been shown to improve glycemic control in patients with diabetes and to alleviate hyperglycemia in selected murine models of diabetes. A novel heat-killed (HK) whole-cell preparation of Mycobacterium aurum (M. aurum) is currently under development as a potential food supplement; nevertheless, its potential bioactivity remains largely unknown. Thus, the present study investigated the potential prophylactic anti-diabetic effects of HK M. aurum in streptozotocin (STZ)-induced diabetic mice. Mice were divided into three groups: the STZ-induced diabetic group was injected with a single intraperitoneal high dose of STZ, the HK M. aurum-treated diabetic group was prophylactically treated with three doses of HK M. aurum 6 weeks before STZ injection, and the control non-diabetic group was given three intradermal injections of borate-buffered saline and an intraperitoneal injection of citrate buffer. Liver lactate dehydrogenase (LDH), uncoupling protein 2 (UCP2), and glucose transporter 2 (GLUT2) and skeletal muscle LDH, UCP3, and GLUT4 protein expression levels in different mouse groups were determined by Western blot. Our results indicated that HK M. aurum did not cause any significant changes in glycemic levels of normal non-diabetic mice. Prophylactic administration of three doses of HK M. aurum to diabetic mice resulted in a significant reduction in their blood glucose levels when compared to those in control diabetic mice. Prophylactic treatment of diabetic mice with HK M. aurum significantly restored their disturbed protein expression levels of liver UCP2 and LDH as well as of skeletal muscle UCP3. On the other hand, prophylactic treatment of diabetic mice with HK M. aurum had no significant effect on their liver GLUT2 and skeletal muscle GLUT4 and LDH protein expression levels. Our findings provide the first evidence that HK M. aurum possesses a hyperglycemia-lowering capacity and might support its future use as a food supplement for the amelioration of diabetes.

The role of pantothenic acid in alleviating hypoxia-induced liver injury of sub-adult grass carp (Ctenopharyngodon idellus): Possible mechanisms and implication

In aquaculture, hypoxia poses a significant threat to fish growth and survival. Despite this, there is limited research on the impact of pantothenic acid (PA) in enhancing the anti-hypoxia stress capability of fish. The primary objective of this study was to explore the effects and potential mechanisms of PA in alleviating hypoxia-induced liver injury in sub-adult grass carp. To achieve this, six experimental diets containing varying levels of PA (0.08, 11.95, 24.95, 37.95, 50.95, and 63.95 mg/kg) were formulated and administered to grass carp (initial weight 696.22 ± 2.45 g) for 63 days. Following the dietary intervention, the fish were segregated into hypoxia and control groups and treated for 96 h. The findings revealed that optimal PA levels could enhance the growth performance of sub-adult grass carp and ameliorate the adverse impacts of hypoxia. First, optimal PA levels reduced serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and lactate dehydrogenase (LDH), as well as mitigated hepatocyte vacuolization, improved liver and mitochondrial morphology, thereby alleviating hypoxia-induced liver injury. Furthermore, optimal PA levels were associated with increased contents of serum cortisol, glucose, liver glycogen, pyruvate, and the activities of Pantothenate kinase 2 (PanK2) and coenzyme A (CoA), while liver lactate content and LDH activity were reduced, indicating improvements in energy metabolism and PA utilization, potentially mediated by the down-regulation of hypoxia-inducible factor-1α (HIF-1α) mRNA level. Moreover, optimal PA levels decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, enhanced liver antioxidant capacity, down-regulated autophagy-related gene mRNA levels, and up-regulated autophagy receptor protein 62 (p62) protein level, suggesting a reduction in oxidative damage and autophagy. Finally, a rise in levels of mitochondrial quality control-related mRNAs such as mitofusin 1/2 (MFN1/2), dynamin-related protein-1 (DRP-1), and nuclear respiratory factor 1/2 (Nrf-1/2) was observed, together with increment in the protein levels of PTEN induced putative kinase 1 (PINK1), BCL-2 interacting protein 3 (BNIP3) and FUN14 domain-containing protein 1 (FUNDC1). These alterations hinted at the role of PA in preserving mitochondrial homeostasis. In conclusion, PA exhibited a protective role against hypoxia-induced liver injury by enhancing liver energy metabolism, bolstering antioxidant defenses, suppressing autophagy, and maintaining mitochondrial homeostasis. Through an assessment of percentage weight gain (PWG) and liver ROS level, the requirements of PA for promoting growth and resilience to hypoxia-induced liver injury in sub-adult grass carp were determined to be 37.44 mg/kg and 42.57 mg/kg, respectively.

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

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

Catalytic Properties of Lactate Dehydrogenase in Skeletal Muscles and Liver of the Marsh Frog (Pelophylax ridibundus) Depend on Its Ecologo-Geographical Habitats

Catalytic Properties of Lactate Dehydrogenase in Skeletal Muscles and Liver of the Marsh Frog (Pelophylax ridibundus) Depend on Its Ecologo-Geographical Habitats

THE CATALYTIC PROPERTIES OF LACTATE DEHYDROGENASE IN SKELETAL MUSCLES AND LIVER OF THE MARSH FROG (PELOPHYLAX RIDIBUNDUS) DEPEND ON ITS ECOLOGICAL AND GEOGRAPHICAL LOCATION

The marsh frog (Pelophylax ridibundus) has a widespread distribution range, which is due to a variety of adaptations that contribute to the development of tolerance to a wide range of physicochemical environmental factors. Of particular interest are the adaptations of these animals to different levels of oxygen in mid- and high-altitude conditions. In this work, a comparative analysis of the kinetic parameters of lactate dehydrogenase (LDH) in the liver of marsh frogs living in the mountainous and lowland regions of Dagestan was carried out. Animals caught in their habitats were decapitated, the liver and calf muscles were isolated, and they were placed in liquid nitrogen. In the laboratory, the selected tissues were homogenized and mitochondria-free cytosol was obtained by differential centrifugation, in which LDH activity was determined. It was found that LDH activity is significantly higher in the tissues of frogs from mountainous regions: by 42.4% in the muscles and 2.38 times in the liver (p 0.05). The high efficiency of catalysis is ensured due to significant changes in the catalytic parameters of the enzyme: an increase in Vmax (50.9% in muscles and 70% in the liver (p 0.05)) and a decrease in Km. (45.9% in muscles and 69% in liver, (p 0.05)). A more pronounced difference, compared to muscles, between LDH activity in the liver of foothill and lowland populations of frogs suggests that the sensitivity of liver LDH to changes in oxygen tension is higher. The vector of a number of other kinetic parameters of LDH (Ki, Sopt, Δ) in the liver of animals from mountainous landscapes is absolutely opposite to that of skeletal muscles. High activity and modifications of the catalytic properties of LDH in the tissues of marsh frogs living in mid-mountain areas may play an important role in the adaptation of these animals to conditions of oxygen deficiency.

Effect of Sublethal Concentrations of Nuvan on Enzymatic Profile of <I>Labeo rohita </I>(ham.)

Toxic effects of sublethal concentrations of nuvan on acid phosphatase (ACP), alkaline phosphatase (ALP), adenosine triphosphatase (ATPase), succinic dehydrogenase (SDH), lactic dehydrogenase (LDH) and acetyl cholinestrase (AChE) activities were studied in fingerlings of Labeo rohita. Two sublethal concentrations i.e. 10.3 mg/I and 2.06 mg/l were selected basing on the LCso value of nuvan in rohu for this experiment continuing for a period of 45 days. Sublethal exposures at two concentrations reduced the brain AChE, and brain, liver and kidney LDH and ATPase (P < 0.05) over a period of 45 days. The reduction of SDH was detected in all the organs examined except brain on 30 day at 2.06 mg/I. While ALP and AChE activities of brain were decreased, the ACP activity was increased.

Protective role of selenium and selenium-nanoparticles against multiple stresses in Pangasianodon hypophthalmus.

Pollution and climate change pose significant threats to aquatic ecosystems, with adverse impacts on aquatic animals, including fish. Climate change increases the toxicity of metal in aquatic ecosystems. To understand the severity of metal pollution and climate change, an experiment was conducted to delineate the mitigation potential of selenium (Se) and selenium nanoparticles (Se-NPs) against lead (Pb) and high temperature stress in Pangasianodon hypophthalmus.For the experiment, five isonitrogenous and isocaloric diets were prepared, varying in selenium supplementation as Se at 0, 1, and 2 mg kg-1 diet, and Se-NPs at 1 and 2 mg kg-1 diet. The fish in stressor groups were exposed to Pb (1/20th of LC50 concentration, 4 ppm) and high temperature (34 °C) throughout the experiment. The results demonstrated that dietary supplementation of Se at 1 and 2 mg kg-1 diet, as well as Se-NPs at 1 mg kg-1 diet, significantly reduced (p< 0.01) the levels of lactate dehydrogenase and malate dehydrogenase in both liver and muscle tissues. Additionally, the levels of alanine aminotransferase and aspartate aminotransferase in both gill and liver tissues were significantly decreased (p< 0.01) with the inclusion of Se and Se-NPs in the diets. Furthermore, the enzymes glucose-6-phosphate dehydrogenase in gill and liver tissues, fructose 1,6-bisphosphatase in liver and muscle tissues, and acid phosphatase in liver tissue were remarkably reduced (p< 0.01) due to the supplementation of Se and Se-NPs. Moreover, dietary supplementation of Se and Se-NPs significantly enhanced (p< 0.01) the activity of pyruvate kinase, glucokinase, hexokinase, alkaline phosphatase, ATPase, protease, amylase, lipase, and RNA/DNA ratio in the fish. Histopathological examination of gill and liver tissues also indicated that Se and Se-NPs protected against structural damage caused by lead and high-temperature stress. Moreover, the study examined the bioaccumulation of selenium and lead in muscle, water, and diets. The aim of the study revealed that Se and Se-NPs effectively protected the fish from lead toxicity and high-temperature stress, while also improving the function of cellular metabolic enzymes in P. hypophthalmus.

The Effects of Acute Exposure to Ammonia on Oxidative Stress, Hematological Parameters, Flesh Quality, and Gill Morphological Changes of the Large Yellow Croaker (Larimichthys crocea).

Ammonia is considered to be the major chemical pollutant causing fish poisoning in aquaculture. This research aimed to evaluate the impact of acute ammonia exposure on the large yellow croaker's meat quality, gill morphology, liver oxidative stress, and hematological parameters. The fish were exposed to total ammonia nitrogen concentrations of 0, 2.96, 5.92, and 8.87 mg/L for 48 h, respectively. The findings demonstrated that all ammonia-exposed fish had higher liver lactate dehydrogenase and glutamic oxalate transaminase activities. The glucose, blood urea nitrogen, and creatinine levels in 8.87 mg/L total ammonia nitrogen (TAN) were higher than other samples. The total protein, albumin, and triglyceride levels in serum decreased significantly in ammonia-exposed samples. After 48 h of ammonia exposure, superoxide dismutase activities showed a 76.1%, 118.0%, and 156.8% increase when fish were exposed to 2.96, 5.92, and 8.87 mg/L TAN, respectively. Catalase activities and glutathione contents were considerably higher (p < 0.05) in all ammonia-treated samples compared to 0 mg/L TAN. The ammonia-treated gill lamellae become thicker, shorter, and curved. Additionally, the ammonia exposure resulted in the accumulation of free amino acids and the loss of nucleotides. The inosine monophosphate and adenosine monophosphate contents in the flesh were decreased after 12 h of exposure to 2.96, 5.92, and 8.87 mg/L ammonia compared to the control group. Overall, large yellow croakers exposed to ammonia for 6 h presented not only changes in serum composition but also oxidative stress, liver and gill tissue damage and flesh quality deterioration.

Toxic Effect of Silver Nanoparticles on Liver, Gill and Muscle Tissues of Zebrafish &lt;i&gt;Danio rerio&lt;/i&gt;

The present study was aimed to evaluate the toxic effect of Silver nanoparticle on the liver, gill and muscle tissues of the Zebrafish, Danio rerio. The experiment was designed to understand the chronic toxicity of silver nanoparticles (AgNPs) in adult fish, Danio rerio. In the chronic toxicity study adult fish, Danio rerio were divided in to two groups. First group was experimental group in which fish were successively treated with a graded series of 0.3, 0.6, 0.9 mg/l an average 60 nm. PVP. coated AgNPs treatment were given for 21 days, at the end of experimental period, Reduced glutathione activity (GSH), Lipid peroxidation activity (LPO), Lactate dehydrogenase (LDH) and Total protein in liver, gill and muscle tissues were assayed. Second group were kept as a control which was free from AgNPs exposure. The levels of Reduced glutathione activity (GSH) and Total protein were found to be decreased were as Lipid peroxidation activity (LPO) and Lactate dehydrogenase activity (LDH) were found to be elevated in liver, gill and muscle tissue of AgNPs treated Zebrafish Danio rerio.

Metabolic rate increases with acclimation temperature and is associated with mitochondrial function in some tissues of threespine stickleback.

The metabolic rate (ṀO2) of eurythermal fishes changes in response to temperature, yet it is unclear how changes in mitochondrial function contribute to changes in ṀO2. We hypothesized that ṀO2would increase with acclimation temperature in the threespine stickleback (Gasterosteus aculeatus) in parallel with metabolic remodeling at the cellular level but that changes in metabolism in some tissues, such as liver, would contribute more to changes in ṀO2than others. Threespine stickleback were acclimated to 5, 12 and 20°C for 7 to 21 weeks. At each temperature, standard and maximum metabolic rate (SMR and MMR, respectively), and absolute aerobic scope (AAS) were quantified, along with mitochondrial respiration rates in liver, oxidative skeletal and cardiac muscles, and the maximal activity of citrate synthase (CS) and lactate dehydrogenase (LDH) in liver, and oxidative and glycolytic skeletal muscles. SMR, MMR and AAS increased with acclimation temperature, along with rates of mitochondrial phosphorylating respiration in all tissues. Low SMR and MMR at 5°C were associated with low or undetectable rates of mitochondrial complex II activity and a greater reliance on complex I activity in liver, oxidative skeletal muscle and heart. SMR was positively correlated with cytochrome c oxidase (CCO) activity in liver and oxidative muscle, but not mitochondrial proton leak, whereas MMR was positively correlated with CCO activity in liver. Overall, the results suggest that changes in ṀO2in response to temperature are driven by changes in some aspects of mitochondrial function in some, but not all, tissues of threespine stickleback.

Expression Levels and Activity of Rat Liver Lactate Dehydrogenase Isoenzymes in Alloxan Diabetes

Expression Levels and Activity of Rat Liver Lactate Dehydrogenase Isoenzymes in Alloxan Diabetes

Clinical significance of respiratory virus coinfection in children with Mycoplasma pneumoniae pneumonia

BackgroundThe prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia has been increasing. However, few studies have investigated the impact of respiratory virus coinfection in patients with MP pneumonia, and their results have been inconclusive. This study aimed to investigate the impact of respiratory virus coinfection in children hospitalized with MP pneumonia.MethodsThis study enrolled 145 children hospitalized with MP pneumonia between May 2019 and March 2020. The patients were divided into two groups: the respiratory virus coinfection and non-coinfection groups. All the children underwent polymerase chain reaction testing for respiratory virus infection. Information on clinical, laboratory, and radiologic findings were obtained retrospectively via medical chart reviews.ResultsChildren in the respiratory virus coinfection group were younger than those in the non-coinfection group. Respiratory virus coinfection in children hospitalized with MP pneumonia was significantly associated with persistence of fever more than 6 days (adjusted odds ratio [aOR], 2.394; 95% confidence interval [95% CI], 1.172–4.892), severe pneumonia (aOR, 4.602; 95% CI, 1.154–18.353), and poor response to the stepwise approach for MP pneumonia (aOR, 4.354; 95% CI, 1.374–13.800). In addition, higher levels of liver enzymes and lactate dehydrogenase at admission were associated with respiratory virus coinfection in children with MP pneumonia.ConclusionsThe results of this study suggest that respiratory virus coinfection in children hospitalized with MP pneumonia may be associated with refractory MP pneumonia.

Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways.

Better biomarkers to predict death early in acute liver failure (ALF) are needed. To that end, we obtained early (study day 1) and later (day 3) serum samples from transplant-free survivors (n = 28) and nonsurvivors (n = 30) of acetaminophen-induced ALF from the NIH-sponsored Acute Liver Failure Study Group and from control volunteers (n = 10). To identify proteins that increase early in serum during ALF, we selected individuals from this cohort for whom alanine aminotransferase was lower on day 1 than day 3, indicating a time point before peak injury (n = 10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1682 quantifiable proteins, 361 were ≥ 4-fold elevated or decreased in ALF patients versus controls and 16 of those were further elevated or decreased ≥ 4-fold in nonsurvivors versus survivors, indicating potential to predict death. Interestingly, 1 of the biomarkers was lactate dehydrogenase (LDH), which is already measured in most clinical laboratories. To validate our proteomics results and to confirm the prognostic potential of LDH, we measured LDH activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the nonsurvivors versus survivors on both days. In addition, it had prognostic value similar to the model for end-stage liver disease and outperformed the King's College Criteria, while a combination of model for end-stage liver disease and LDH together outperformed either alone. Finally, bioinformatics analysis of our proteomics data revealed alteration of numerous signaling pathways that may be important in liver regeneration. Overall, we conclude LDH can predict death in APAP-induced ALF.

Expression levels and activity of rat liver lactate dehydrogenase isoenzymes in alloxan diabetes

A significant decrease in the activity of lactate dehydrogenase (LDH, EC 1.1.1.27) in liver cells of rats with alloxan diabetes was found due to a decrease in the expression of the corresponding genes. The decrease in the activity of the enzyme under study in experimental type I diabetes was associated with inactivation of the cytoplasmic isoform of LDH. It was found that the level of ldha and ldhb gene transcripts in the liver of healthy rats was higher than in animals with alloxan diabetes. The ldha gene expression demonstrated almost 9-fold decrease, while a decrease in the ldhb gene expression was less pronounced (just 1.25-fold). Probably, the decrease in the rate of functioning of the enzyme under study is associated with a decrease in the intensity of glucose uptake by cells, which leads to inhibition of glycolysis and intensification of all stages of gluconeogenesis, particularly, reversed glycolysis reactions. Thus, the data obtained by us indicate an important role of LDH in the adaptive response of cellular metabolism in the development of type I diabetes mellitus.

Expression levels and activity of rat liver lactate dehydrogenase isoenzymes in alloxan diabetes

A significant decrease in the activity of lactate dehydrogenase (LDH, EC 1.1.1.27) in liver cells of rats with alloxan diabetes was found due to a decrease in the expression of the corresponding genes. The decrease in the activity of the enzyme under study in experimental type I diabetes was associated with inactivation of the cytoplasmic isoform of LDH. It was found that the level of ldha and ldhb gene transcripts in the liver of healthy rats was higher than in animals with alloxan diabetes. The ldha gene expression demonstrated almost 9-fold decrease, while a decrease in the ldhb gene expression was less pronounced (just 1.25-fold). Probably, the decrease in the rate of functioning of the enzyme under study is associated with a decrease in the intensity of glucose uptake by cells, which leads to inhibition of glycolysis and intensification of all stages of gluconeogenesis, particularly, reversed glycolysis reactions. Thus, the data obtained by us indicate an important role of LDH in the adaptive response of cellular metabolism in the development of type I diabetes mellitus.V pecheni krys s alloksanovym diabetom obnaruzheno znachitel'noe snizhenie aktivnosti laktatdegidrogenazy (LDG, KF 1.1.1.27), obuslovlennoe umen'sheniem ékspressii sootvetstvuiushchikh genov. Éto snizhenie aktivnosti LDG, po-vidimomu, sviazano s umen'sheniem urovnia tsitoplazmaticheskoĭ izoformy LDG. Vyiavleno, chto kontsentratsiia transkriptov genov ldha i ldhb v pecheni zdorovykh krys vyshe, chem u zhivotnykh s alloksanovym diabetom. Prichem ékspressiia gena ldha byla snizhena pochti v 9 raz, togda kak ékspressiia gena ldhb snizhalas' vsego lish' v 1,25 raza. Poluchennye nami dannye svidetel'stvuiut o vazhnoĭ roli LDG v adaptivnoĭ reaktsii kletochnogo metabolizma pri razvitii sakharnogo diabeta I tipa.

Ameliorative Effect of Annona m uricata Leaf Extract on Fipronil Induced Liver Biochemical Alterations in Oreochromis m ossambicus

The diverse array of pharmacological properties present in the natural compounds of Annona muricata and its wide use in traditional medicine have all been prime area of research focus. The present study was undertaken to focus on the hepatoprotective role of Annona muricata leaf extract in Oreochromis mossambicus exposed to fipronil toxicity for 15 and 30 days. The study of fipronil toxicity in antioxidant/detoxification enzymes in liver such as Catalase (CAT), Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP), Acid phosphatase (ACP) and Lactate dehydrogenase (LDH) is an attempt to provide a clear concept of hepatic toxicity of fipronil. Fishes were exposed to 3 sublethal concentrations (1/5, 1/10, 1/15) of fipronil for 15 and 30 days fed with normal and plant extract supplement feed. The antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) showed decreased activity on exposure to fipronil for 15 days and 30 days. The A.muricata supplemented group also showed decreased activity significant and dose-dependent but this decrease in activity was less when compared to fipronil exposed groups fed with normal feed. This indicates the stressed condition of O.mossambicus on exposure to fipronil that was reduced in A.muricata extract supplemented groups indicating the ameliorative effect of leaf extract. The liver enzymes AST, ALT, ALP, ACP and LDH showed increased activity for all concentrations for 15 and 30 days of fipronil exposure. A. muricata supplemented groups also showed increased liver enzyme levels but this increase was less when compared with fishes fed with normal feed. The increase in activity was significant and dose-dependent. This reveals liver damage alteration in liver activity when exposed to fipronil whereas fipronil exposed groups fed with plant extract supplement showed a recovery of chronic toxicity as evidenced by the liver enzyme activity.

Amelioration of Cisplatin-induced Liver Injury by Extract Ethanol of Pometia pinnata

BACKGROUND: Cisplatin use in clinical practice has been associated with an increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and lactate dehydrogenase (LDH). AIM: The aim of this study is to determine the hepatoprotective activity of extract ethanol Pometia pinnata on rats induced Cisplatin. MATERIALS AND METHODS: Thirty rats were separated into six groups (five rats). Group I was received only carboxy methyl cellulose. Group II was received a 7 mg/kgbw Cisplatin injection on day 3. Group III-VI were extract groups (Vitamin C 1%, 100 mg/kgbb, 200 mg/kgbb, and 400 mg/kgbb) administered orally from day 1 to 7, followed by Cisplatin injection on day 3. On day 8, rats were injected with 1% ketamine, open the chest and draw blood directly from the heart and centrifugated 5000 RPM (10–15 min), take the supernatant layer for analysis AST, ALT, total protein, and LDH levels. RESULTS: The effect of extract ethanol of P. pinnata on liver injury biochemical markers AST, ALT, LDH, and total protein. Group negative had a significant increase (p &lt; 0.05) in comparison to the normal that did not receive extract or Cisplatin. Meanwhile, there was a drop in biochemical parameters in the group given the extract in groups dose 100, 200, 400 mg/kgbw. Group VI of biochemical parameters statistically there is no significant different with group normal group (p &gt; 0.05) that showing P. pinnata extract has hepatoprotective activity. CONCLUSION: In summary, extract ethanol of P. pinnata has hepatoprotective effect by reducing the level of AST, ALT, total protein, and LDH levels.

In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [1-13 C]Pyruvate and Proton Density Fat Fraction in a Guinea Pig Model of Non-Alcoholic Fatty Liver Disease Development After Life-Long Western Diet Consumption.

Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. Prospective. Twenty-eight male guinea pigs weaned onto a control diet (N=14) or WD (N=14). 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. Median PDFF was calculated in the liver and hind limbs. [1-13 C]pyruvate dynamic MRS in the liver was quantified by the time-to-peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. Unpaired Student's t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. 2 TECHNICAL EFFICACY STAGE: 1.

A147 PRIMARY COLONIC MANTLE CELL LYMPHOMA: A RARE ENTITY

Abstract Background Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL), often diagnosed at later stages with secondary gastrointestinal (GI) involvement. Primary GI MCL is rare and is not often discussed in the literature. Aims To increase awareness of a rare condition that is likely to be encountered but can be challenging to diagnose. Methods Case report and review of the literature. Results Case Report A 78-year-old man with multiple untreated vascular risk factors including atrial fibrillation and type 2 diabetes presented with acute onset left hemiplegia, dysarthria, and imaging consistent with a left pontine stroke. As part of his workup he underwent a CT abdomen/pelvis identifying an 11 x 5 cm intraluminal mass in the transverse colon. Previous screening colonoscopies, for family history of colon cancer, were notable for tubular adenomas without high-grade dysplasia at 13, 12, 10, 7, and 2 years prior to admission. The patient had 16 pounds of weight loss without other constitutional symptoms, change in bowel habits or evidence of GI bleeding. Bloodwork was notable for microcytic anemia (Hemoglobin 91 g/L, MCV 75 fL), from a normal baseline one year prior, without other cytopenias. C-reactive protein (44 mg/L) and GGT (164 U/L) were elevated. Other liver enzymes, lactate dehydrogenase, and electrolytes were normal. Colonoscopy revealed numerous polypoid lesions throughout the entire colon and a large non-obstructive mass with submucosal appearance in the transverse colon. Biopsies were taken from the large mass and one of the smaller polypoid lesions. Histology showed a sheet-like infiltrate of small lymphocytes within the lamina propria. Immunohistochemical staining was positive for CD20, BCL2, Cyclin D1, equivocal for CD5, and negative for BCL6 and CD3. Ki67 index approached 30%. A diagnosis of colonic MCL was made. Literature Review Primary MCL of the GI tract is rare, accounting for only 1 to 4% of all GI malignancies. There is a male and Caucasian predominance with a median age of 68 years at diagnosis. Presenting complaints may include abdominal pain, anorexia, and GI bleeding. Typical endoscopic features are small nodular or polypoid tumors, between 2mm and 2 cm in size, along one or more segments of the GI tract referred to as multiple lymphomatous polyposis (MLP). A single colonic mass is infrequently seen, highlighting the importance of endoscopy for diagnosis, as subtle findings may be missed on radiographic evaluation. Biopsies for immunohistochemistry are essential to distinguish MCL from other NHLs, as almost all cases express cyclin D1. Despite aggressive immunochemotherapy, prognosis is often poor due to MCL’s rapid progression and early relapse. Conclusions Primary GI MCL is a rare entity. Awareness is essential as evaluation and management differ from lymphoma at other sites, and other GI malignancies. Funding Agencies None

Biological Evaluation of Azetidine-2-One Derivatives of Ferulic Acid as Promising Anti-Inflammatory Agents

The purpose of this study was to evaluate the in vivo biological potential of new azetidine-2-one derivatives of ferulic acid (6a–f). First, the in vivo acute toxicity of azetidine-2-one derivatives of ferulic acid on Swiss white mice was investigated and, based on the obtained results, it can be stated that the studied derivatives belong to compounds with moderate toxicity. The in vivo anti-inflammatory potential of these derivatives was determined in a model of acute inflammation induced by carrageenan in rats and in a chronic inflammation model induced in rats using the granuloma test. In the acute inflammation model, all the studied compounds had a maximum anti-inflammatory effect 24 h after administration, which suggests that these compounds may be classified, from a pharmacokinetic point of view, in the category of long-acting compounds. The most active compound in the series was found to be compound 6b. In the case of the chronic inflammation model, it was observed that the studied compounds (6a–f) reduced the formation of granulation tissue compared to the control group, having an intense effect of inhibiting the proliferative component. The most important inhibitory effect of inhibiting the proliferative component was recorded for compound 6b. Additionally, the investigation of liver function was performed by determining the serum levels of liver enzymes aspartate transaminase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and bilirubin (total and direct). The results showed that, in the series of azetidin-2-one derivatives, the liver enzymes concentration values were close to those recorded for the reference anti-inflammatories (diclofenac sodium and indomethacin) and slightly higher compared to the values for the healthy control group. At the end of the experiment, the animals were euthanized and fragments of liver, lung, and kidney tissue were taken from all groups in the study. These were processed for histopathological examination, and we noticed no major changes in the groups treated with the azetidine 2-one derivatives of ferulic acid compared to the healthy groups.