Plasma Enzyme Research Articles

Progesterone Has No Impact on the Beneficial Effects of Estradiol Treatment in High-Fat-Fed Ovariectomized Mice

In recent decades, clinical and experimental studies have revealed that estradiol contributes enormously to glycemic homeostasis. However, the same consensus does not exist in women during menopause who undergo replacement with progesterone or conjugated estradiol and progesterone. Since most hormone replacement treatments in menopausal women are performed with estradiol (E2) and progesterone (P4) combined, this work aimed to investigate the effects of progesterone on energy metabolism and insulin resistance in an experimental model of menopause (ovariectomized female mice-OVX mice) fed a high-fat diet (HFD). OVX mice were treated with E2 or P4 (or both combined). OVX mice treated with E2 alone or combined with P4 displayed reduced body weight after six weeks of HFD feeding compared to OVX mice and OVX mice treated with P4 alone. These data were associated with improved glucose tolerance and insulin sensitivity in OVX mice treated with E2 (alone or combined with P4) compared to OVX and P4-treated mice. Additionally, E2 treatment (alone or combined with P4) reduced both hepatic and muscle triglyceride content compared with OVX control mice and OVX + P4 mice. There were no differences between groups regarding hepatic enzymes in plasma and inflammatory markers. Therefore, our results revealed that progesterone replacement alone does not seem to influence glucose homeostasis and ectopic lipid accumulation in OVX mice. These results will help expand knowledge about hormone replacement in postmenopausal women associated with metabolic syndrome and non-alcoholic fatty liver disease.

Interaction between Changan Granule and its main components in the plasma and CYP450 enzymes.

Changan Granule (CAG) is a Chinese patent drug developed based on an empirical prescription in accordance with the formulation theory of Traditional Chinese Medicine. The prescription is composed of eight herbal drugs which have been traditionally used by Chinese people for a long history. It has effects of invigorating spleen and supplementing qi, as well as regulating liver and ceasing diarrhea, and is indicated for the treatment of irritable bowel syndrome (IBS). This study was aimed to investigate the interaction between CAG and its main components and cytochrome P450 (CYP450) enzymes so as to characterize the major metabolites and metabolic enzymes and evaluate the safety concerns to its clinical use. Both in vivo and in vitro experiments using such as diarrhea-predominant IBS (IBS-D) rat model, HepG2 cells, and human liver microsomes (HLM) were carried out to investigate the interaction between CAG and its main components and CYP450 enzymes. Real-time quantitative PCR (qPCR), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and cocktail probes were employed to qualitatively or quantitatively measure the metabolites and metabolic enzymes. CAG inhibited the enzyme activities of CYP1A2, CYP2E1, CYP2D6, CYP2C9, and CYP3A4 and the mRNA expressions of CYP2E1, CYP2C9, CYP3A4, and CYP2D6 in vitro. CAG down-regulated the increased expression of CYP1A2 and up-regulated the decreased expression of CYP3A1 in vivo. Twenty-two metabolites were characterized from the main components of CAG after incubation with HLM in vitro. CYP2D6, CYP2E1, CYP3A4 and CYP2C9 were identified as the characteristic metabolic enzymes. This study provides a reference for clinical application of CAG in safety. CAG and CYP450 enzymes are interacted. CAG is mainly metabolized by CYP2E1 and CYP2D6. The expression of CYP2E1 and CYP2D6 are more susceptible to be influenced by CAG in comparison with that of CYP3A4, CYP2C9 and CYP1A2. It implies the potential risk of interaction when CAG is taken together with the drugs metabolized by CYP2E1 and CYP2D6.

Vutiglabridin Modulates Paraoxonase 1 and Ameliorates Diet-Induced Obesity in Hyperlipidemic Mice.

Vutiglabridin is a clinical-stage synthetic small molecule that is being developed for the treatment of obesity and its target proteins have not been fully identified. Paraoxonase-1 (PON1) is an HDL-associated plasma enzyme that hydrolyzes diverse substrates including oxidized low-density lipoprotein (LDL). Furthermore, PON1 harbors anti-inflammatory and antioxidant capacities and has been implicated as a potential therapeutic target for treating various metabolic diseases. In this study, we performed a non-biased target deconvolution of vutiglabridin using Nematic Protein Organisation Technique (NPOT) and identified PON1 as an interacting protein. We examined this interaction in detail and demonstrate that vutiglabridin binds to PON1 with high affinity and protects PON1 against oxidative damage. Vutiglabridin treatment significantly increased plasma PON1 levels and enzyme activity but not PON1 mRNA in wild-type C57BL/6J mice, suggesting that vutiglabridin modulates PON1 post-transcriptionally. We further investigated the effects of vutiglabridin in obese and hyperlipidemic LDLR-/- mice and found that it significantly increases plasma PON1 levels, while decreasing body weight, total fat mass, and plasma cholesterol levels. Overall, our results demonstrate that PON1 is a direct, interacting target of vutiglabridin, and that the modulation of PON1 by vutiglabridin may provide benefits for the treatment of hyperlipidemia and obesity.

Severe Obesity in Women Can Lead to Worse Memory Function and Iron Dyshomeostasis Compared to Lower Grade Obesity

Obesity is one of the modifiable risk factors for dementia. Insulin resistance, the abundance of advanced glycated end-products, and inflammation are some of the mechanisms associated with the lower cognitive performance observed in obesity. This study aims to evaluate the cognitive function of subjects with distinct degrees of obesity, comparing class I and II obesity (OBI/II) to class III obesity (OBIII), and to investigate metabolic markers that can distinguish OBIII from OBI/II. Study Design. This is a cross-sectional study, in which 45 females with BMI varying from 32.8 to 51.9 kg/m2 completed a set of 4 cognitive tests (verbal paired-associate test, stroop color, digit span, and Toulouse-Pieron cancellation test) and their plasma metabolites, enzymes, and hormones related to glycemia, dyslipidemia, and liver function, as well as the biomarkers of iron status, were concomitantly analyzed. OBIII showed lower scores in the verbal paired-associate test compared to OBI/II. In other cognitive tests, both groups showed similar performance. OBIII presented a lower iron status compared to OBI/II based on total iron binding capacity, degree of transferrin saturation, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. The levels of indicators for glycemia, liver function, and lipid metabolism were similar in both groups. Analysis of plasma metabolites showed that OBIII had lower levels of pyroglutamic acid, myoinositol, and aspartic acid and higher levels of D-ribose than OBI/II. Iron is an essential micronutrient for several metabolic pathways. Thus, iron dyshomeostasis observed in severe obesity may aggravate the cognitive impairment by altering metabolic homeostasis and enhancing oxidative stress. These findings can contribute to searching for biomarkers that indicate cognitive performance in the population with obesity.

Dietary supplementation of multi-strain probiotic in male rainbow trout (Oncorhynchus mykiss) broodstock: Effects on feed efficiency, hemato-biochemical parameters, immune response, and semen quality

The present study aimed to determine the effects of dietary probiotic supplementation on feed efficiency, physiological parameters, and semen quality of male rainbow trout (Oncorhynchus mykiss) broodstock. For this purpose, a total of 48 breeders with an average initial weight of 1366.1 ± 33.8g were divided into 4 groups and 3 replicates. Fish were fed with diets containing 0 (control), 1 × 109 (P1), 2 × 109 (P2), and 4 × 109 (P3) CFU multi-strain probiotic kg-1 diet for 8weeks. According to the results, P2 treatment significantly enhanced body weight increase, specific growth rate, and protein efficiency ratio and decreased feed conversion ratio. Moreover, the highest values of red blood cells count, hemoglobin, and hematocrit values were observed in P2 treatment (P < 0.05). The lowest levels of glucose, cholesterol, and triglyceride were found in P1, P2, and P3 treatments, respectively. Also, the highest levels of total protein and albumin were obtained in P2 and P1 treatments (P < 0.05). Based on the results, plasma enzymes contents were significantly decreased in P2 and P3 treatments. In terms of immune parameters, the complement component 3, complement component 4, and immunoglobulin M levels were increased in all probiotic-fed treatments (P < 0.05). For spermatological features, the highest spermatocrit value, sperm concentration, and motility time were observed in the P2 treatment (P < 0.05). Consequently, we conclude that multi-strain probiotics can be used as functional feed additives in male rainbow trout broodstock to enhance semen quality, improve physiological responses, and better feed efficiency.

Antioxidant Activity of Different Tissues from Rabbits Fed Dietary Bovine Colostrum Supplementation

Recent advances in animal nutrition have indicated that bovine colostrum (BC), due to its content of macronutrients, micronutrients and bioactive compounds, is an excellent health supplement. To the best of our knowledge, no studies on the effect of BC on antioxidant status have been performed in rabbits. This study aimed to investigate the effect of two BC concentrations on antioxidant status and gene expression of antioxidant enzymes in some tissues of rabbits. Thirty New Zealand White male rabbits were randomly divided into three experimental diets, containing 0% (CON), 2.5%, and 5% of BC (BC-2.5 and BC-5, respectively). The activity of antioxidant enzymes in plasma (catalase: CAT; glutathione peroxidase: GPx; superoxide dismutase: SOD), and the enzymes' gene expression in the liver and longissimus dorsi muscle, were determined. Results showed no significant differences, neither in plasma nor in tissues. A significant tissue-related effect has been observed regarding the mRNA levels of SOD and GPx, which were higher in the LD (p = 0.022) and liver (p = 0.001), respectively. Further studies, considering modifications of the length and dosage of dietary BC supplementation, are required to update the current state of knowledge in rabbits, as well as to fully understand the potential value of BC for possible application in farming use.

The effects of Chinese herbal feed additives on physiological health and detoxification ability in the red claw crayfish, Cherax quadricarinatus, and evaluation of their safety

The side effects of Chinese herbal medicine on metabolism in aquatic animals have not been fully studied. This study focused on evaluating the effects of Astragalus polysaccharide, chlorogenic acid, and berberine on the physiological health and detoxification ability of Cherax quadricarinatus. A basic diet served as a control, and diets containing differing concentrations of Astragalus polysaccharide (1, 2, 4, 8 g/kg), chlorogenic acid (1, 2, 4, 8 g/kg), or berberine (0.1, 0.5, 2.5 g/kg) were prepared. One thousand and eight crayfish (28.83 ± 0.29 g) were randomly allocated to 12 groups of net cages for 14 days. Samples were taken 7 days after feeding with Chinese herb bioactive ingredients and 7 days after ceasing this feeding. The results showed that compared with the control group, the addition of Astragalus polysaccharide, chlorogenic acid, or berberine did not have a significant effect on the growth performance of each experimental group. Cellular immunity, humoral immunity and antioxidant enzyme activities were increased significantly, while the concentrations of three herbal bioactive ingredients in plasma and metabolic enzymes improved significantly. Moreover, the bioactive ingredients did not cause biological macromolecular damage or histological damage in the hepatopancreas and significantly reduced the content of malondialdehyde. However, high concentrations of berberine (2.5 g/kg) significantly increased alanine aminotransferase and aspartate aminotransferase activities in the hepatopancreas, which could have a potential risk of damage to the hepatopancreas. Our results indicated that Astragalus polysaccharide, chlorogenic acid, and 0.1 g/kg berberine can be used as safe feed additives to stimulate the immune response, antioxidant capacity and detoxification ability and protect the organism from damage under oxidative stress.

Cumulative effects of paraoxon and leptin on oxidative damages in rat tissues: prophylactic and therapeutic roles of N-acetylcysteine

Exposure to paraoxon (POX) and leptin (LP) could cause an imbalance between oxidants and antioxidants in an organism, which can be prevented by introduction of exogenous antioxidants such as N-acetylcysteine (NAC). The aim of this study was to evaluate synergic or additive effects of administration of exogenous LP plus POX on the antioxidant status, as well as the prophylactic and therapeutic roles of NAC in various rat tissues. Fifty-four male Wistar rats were divided into nine groups treated with different compounds: Control (no treatment), POX (0.7 mg/kg), NAC (160 mg/kg), LP (1 mg/kg), POX + LP, NAC-POX, POX-NAC, NAC-POX + LP, and POX + LP-NAC. In the last five groups, only the order of administered compounds differed. After 24 h, plasma and tissues were sampled and examined. The results showed that administration of POX plus LP significantly increased biochemical indices in plasma and antioxidant enzymes activities and decreased glutathione content in the liver, erythrocytes, brain, kidney, and heart. In addition, cholinesterase and paraoxonase 1 activities in the POX + LP-treated group were decreased and malondialdehyde level was increased in the liver, erythrocytes, and brain. However, administration of NAC rectified induced changes although not to the same extent. Our study suggests that POX or LP administration engage the oxidative stress system per se; however, their combination did not produce significantly greater effects. Moreover, both prophylactic and therapeutic treatments of rats with NAC supported the antioxidant defense against oxidative damage in tissues, most probably through both its free radical scavenging ability and maintaining intracellular GSH levels. It can therefore be suggested that NAC has particularly protective effects against POX or/and LP toxicity.

Ecological shifts of salivary microbiota associated with metabolic-associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease related to metabolic syndrome. However, ecological shifts in the saliva microbiome in patients with MAFLD remain unknown. This study aimed to investigate the changes to the salivary microbial community in patients with MAFLD and explore the potential function of microbiota. Salivary microbiomes from ten MAFLD patients and ten healthy participants were analyzed by 16S rRNA amplicon sequencing and bioinformatics analysis. Body composition, plasma enzymes, hormones, and blood lipid profiles were assessed with physical examinations and laboratory tests. The salivary microbiome of MAFLD patients was characterized by increased α-diversity and distinct β-diversity clustering compared with control subjects. Linear discriminant analysis effect size analysis showed a total of 44 taxa significantly differed between the two groups. Genera Neisseria, Filifactor, and Capnocytophaga were identified as differentially enriched genera for comparison of the two groups. Co-occurrence networks suggested that the salivary microbiota from MAFLD patients exhibited more intricate and robust interrelationships. The diagnostic model based on the salivary microbiome achieved a good diagnostic power with an area under the curve of 0.82(95% CI: 0.61-1). Redundancy analysis and spearman correlation analysis revealed that clinical variables related to insulin resistance and obesity were strongly associated with the microbial community. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to metabolism were more prevalent in the two groups. Patients with MAFLD manifested ecological shifts in the salivary microbiome, and the saliva microbiome-based diagnostic model provides a promising approach for auxiliary MAFLD diagnosis.

The Impacts of Dietary Curcumin on Innate Immune Responses and Antioxidant Status in Greater Amberjack (Seriola dumerili) under Ammonia Stress

In this study, we investigated the effect of dietary curcumin on non-specific immune responses and antioxidative ability in Seriola dumerili under ammonia stress and post-recovery. Three diets were prepared to contain 0, 75, and 150 mg/kg of curcumin. A total of 225 greater amberjack (initial weight: 100.90 ± 0.03 g) were distributed into nine cylindrical tanks, constituting an experimental design with three treatments and three replicates. After 56 days of feeding, plasma, intestinal, and hepatic enzyme activities were evaluated. Then, an acute ammonia challenge experiment was conducted. Ten fish per tank were subjected to acute ammonia stress (total ammonia-N: 1000 mg/L) for eight minutes followed by six minutes of recovery. The results indicated that dietary curcumin significantly promoted intestinal and hepatic alkaline phosphatase (ALP) and acid phosphatase (ACP) levels as well as hepatic antioxidative enzymes such as superoxide dismutase (SOD), total antioxidant capacity (T-AOC), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) of greater amberjack. In addition, curcumin addition improved the activities of antioxidant enzymes, such as SOD, T-AOC, GSH, GSH-Px, and catalase (CAT), and reduced malondialdehyde (MDA) content in liver, spleen, head kidney, and brain tissues after post-recovery. The indexes related to immunity and antioxidant enzymes in the liver, gill, and spleen rose again to some extent, but they showed the worst recovery ability in the head kidney and brain tissue samples. These results indicate that dietary curcumin supplementation could increase non-specific immune responses, antioxidant ability, and enhance resistance to high ammonia stress in juvenile S. dumerili.

Cumulative Effects of Paraoxon and Leptin on Oxidative Damages in Rat Tissues: Prophylactic and Therapeutic Roles of N-Acetylcysteine

Exposure to paraoxon (POX) and leptin (LP) could cause an imbalance between oxidants and antioxidants in an organism, which can be prevented by introduction of exogenous antioxidants such as N-acetylcysteine (NAC). The aim of this study was to evaluate synergic or additive effects of administration of exogenous LP plus POX on the antioxidant status, as well as the prophylactic and therapeutic roles of NAC in various rat tissues. Fifty-four male Wistar rats were divided into nine groups treated with different compounds: Control (no treatment), POX (0.7 mg/kg), NAC (160 mg/kg), LP (1 mg/kg), POX+LP, NAC-POX, POX-NAC, NAC-POX+LP, and POX+LP-NAC. In the last five groups, only the order of administered compounds differed. After 24 h, plasma and tissues were sampled and examined. The results showed that administration of POX plus LP significantly increased biochemical indices in plasma and antioxidant enzymes activities and decreased glutathione content in the liver, erythrocytes, brain, kidney, and heart. In addition, cholinesterase and paraoxonase 1 activities in the POX+LP-treated group were decreased and malondialdehyde level was increased in the liver, erythrocytes, and brain. However, administration of NAC rectified induced changes although not to the same extent. Our study suggests that POX or LP administration engage the oxidative stress system per se; however, their combination did not produce significantly greater effects. Moreover, both prophylactic and therapeutic treatments of rats with NAC supported the antioxidant defense against oxidative damage in tissues, most probably through both its free radical scavenging ability and maintaining intracellular GSH levels. It can therefore be suggested that NAC has particularly protective effects against POX or/and LP toxicity.

Development and application of a simple pharmacokinetic model that quantitatively describes the distribution and elimination of the commonly measured proteins.

Increased plasma concentrations of a variety of cellular enzymes (alanine transaminase, aspartate aminotransferase, alkaline phosphatase, amylase, etc.) are commonly used as routine screening tests for a range of conditions. An increased concentration usually is assumed to result from an increased rate of delivery to the plasma. Factors such as decreased metabolism or excretion or altered extravascular distribution usually are ignored. As a prelude to a detailed analysis of all the factors producing altered plasma enzyme levels, we have reviewed the relevant literature describing the pharmacokinetics (PK) of 13 of the commonly measured plasma proteins and developed a PK model that provides a simple physiological description of all the data. Our model starts with the general 3-compartment, 6-parameter system previously developed for albumin and interprets the fluxes in terms of unidirectional sieved protein convectional volume flows from the plasma to the two tissue compartments and equal lymph flows returning to the plasma. This greatly constrains the model such that each protein is characterized by only two adjustable parameters (plasma clearance and sieving factor). In addition to accurately fitting the plasma kinetics, the model can accurately describe the tissue and lymph protein PK. For example, it can describe the thoracic duct lymph protein concentration following an intravenous infusion or the plasma concentration following a subcutaneous tissue injection. This simple model provides a satisfactory framework for the PK of 12 of the 13 proteins investigated. The glycoprotein intestinal alkaline phosphatase is the exception, requiring the addition of a liver recycling compartment involving the asialoglycoprotein receptor.

Molecular and Computational Analysis Identify Statins as Selective Inhibitors of Human Butyrylcholinesterase.

Cholinesterase enzyme family consists of acetylcholinesterase (AChE, 3.1.1.7), the major enzyme responsible for hydrolysis of acetylcholine at cholinergic synapses, and butyrylcholinesterase (BChE, 3.1.1.8) a detoxification enzyme of plasma. Statins are cholesterol-lowering medications utilized as protective medicaments in stroke and Alzheimer's disease, which cholinesterases are associated with. Thus, in this study, we characterized the inhibitory effects and mechanisms of common statins, rosuvastatin, atorvastatin, simvastatin and lovastatin, on human erythrocyte AChE and purified serum BChE using in vitro and in silico methods. Kinetic assays identified statins as selective non-competitive inhibitors of human serum BChE. The IC50 and Km values were found as 194.7 ± 55.2 µM and 1.03 ± 0.2 µM for rosuvastatin, 492.5 ± 55.1 µM and 7.2 ± 0.3 µM for atorvastatin, 14.2 ± 0.3 µM and 202.7 ± 23.2 µM for lovastatin, and 17.6 ± 0.1 µM and 207.2 ± 13.2 µM for simvastatin, respectively. The compounds did not display considerable inhibition against AChE. Molecular docking predicted good affinity and strong interactions with the BChE active site for atorvastatin and rosuvastatin. Current study identifies rosuvastatin as the most specific and selective inhibitor of human BChE among the tested statins. As selective inhibitors of BChE statins have the potential to be re-evaluated as medicaments due to their pleiotropic effects.

Embracing enzyme promiscuity with activity-based compressed biosensing

The development of protease-activatable drugs and diagnostics requires identifying substrates specific to individual proteases. However, this process becomes increasingly difficult as the number of target proteases increases because most substrates are promiscuously cleaved by multiple proteases. We introduce a method-substrate libraries for compressed sensing of enzymes (SLICE)-for selecting libraries of promiscuous substrates that classify protease mixtures (1) without deconvolution of compressed signals and (2) without highly specific substrates. SLICE ranks substrate libraries using a compression score (C), which quantifies substrate orthogonality and protease coverage. This metric is predictive of classification accuracy across 140 in silico (Pearson r= 0.71) and 55 invitro libraries (r= 0.55). Using SLICE, we select a two-substrate library to classify 28 samples containing 11 enzymes in plasma (area under the receiver operating characteristic curve [AUROC]= 0.93). We envision that SLICE will enable the selection of libraries that capture information from hundreds of enzymes using fewer substrates for applications like activity-based sensors for imaging and diagnostics.

Cytotoxicity Assays as Predictors of the Safety and Efficacy of Antimicrobial Agents.

The development of safe antimicrobial agents is important for the effective treatment of pathogens. From a multitude of discovered inhibitory compounds, only a few antimicrobial agents are able to enter the market. Many antimicrobials are, on the one hand, quite effective in killing pathogens but, on the other hand, cytotoxic to eukaryotic cells. Cell health can be monitored by various methods. Plasma membrane integrity, DNA synthesis, enzyme activity, and reducing conditions within the cell are known indicators of cell viability and cell death. For a comprehensive overview, methods to analyze cytotoxic and hemolytic effects, e.g., lactate dehydrogenase release, cell proliferation analysis, cell viability analysis based on the activity of different intracellular enzymes, and hemolysis assay of antimicrobial compounds on human cells, are described in this updated chapter.

Resveratrol alleviated 5-FU-induced cardiotoxicity by attenuating GPX4 dependent ferroptosis

The clinical use of 5-fluorouracil (5-FU), a potent antitumor agent, was limited by severe cardiotoxic effects. The present study was aimed to investigate the protective effects of resveratrol (Res) on 5-FU-induced cardiotoxicity and to explore its potential mechanisms.The cardiotoxicity model was intraperitoneal injection of 5-FU at the dose of 30 mg/kg for 7 consecutive days. Plasma enzymes activities, cardiac tissues were assessed after treatment with Res for 3 weeks. Ferrostatin-1 (Fer-1) was used as ferroptosis inhibitor. In H9c2 cardiomyocyte cells, cell viability, generation of reactive oxygen species (ROS), mitochondrial activity and cellular Fe2+ levels were measured. Western-blot assay was performed to evaluate the protein level of ferroptosis in vitro and in vivo. In the mice model, Res reduced 5-FU-induced cardiomyocyte injury (ferroptosis, myofibrillar loss and vacuolization). In addition, increased serum creatine kinase (CK), lactate dehydrogenase (LDH), malonaldehyde (MDA) and Fe2+ activity and decreased activities of glutathione (GSH) were observed in 5-FU group. These changes were prevented by treatment with Res. In H9c2 cardiomyocyte cells, Res increased the cell viability and attenuated cell ferroptosis as measured by DCFH-DA, TMRE and Calcein AM staining. In addition, 5-FU induced a reduction in GPX4, FTH1, Nrf2 and NQO1 and activation of TfR and P53 compared with the control group. However, Res effectively inhibited the changes in ferroptosis associated proteins in vitro and in vivo. Res possessed the cardioprotective potential against 5-FU induced cardiotoxicity. Moreover, Res attenuates 5-FU-induced cardiotoxicity via inhibiting GPX4 dependent ferroptosis.

Lipid composition and oxidative changes in diabetes and alcoholic diabetes rats

BackgroundThe investigating of study was expected to the lipid composition of diabetes and alcoholic diabetes in plasma and erythrocyte membrane biochemical profile in rats. Diabetic male Wistar Streptozotocin (STZ)-induced rats were used experimental models. Control rats (C) were maintained group I, received glucose (i.e., caloric equivalent), diabetic induced rats (STZ) group II, and group III alcoholic treated and IV diabetic and alcoholic treated rats which received 20 % (v/v) alcohol in water, administered through stomach tube (5 g/kg body weight/day). ResultsSTZ-induced diabetic hepatic damage in rats was observed which leads to the increased plasma lipid peroxidation, nitrate and nitrite levels. Diabetic and administration alcohol rats also suggestively lesser the activities of antioxidants, glutathione peroxidase, glutathione S-transferase, superoxide dismutase, catalase and reduced glutathione when related with control rats (group I). Plasma enzymes are normal levels and renovate the enzymic and non-enzymatic antioxidants level in experimental groups. ConclusionThe present data point out that the nitric oxide scavenging levels increased and may possibly protect and adjacent to oxidative stress and free radicals in diabetic hepatopathy rats and histopathological studies were identified in regular hepatic cortex of Group II, III and IV of animals with diabetes, alcoholic and alcohol-induced diabetes rats.

Aqueous extract of bay leaf (Laurus nobilis) ameliorates testicular toxicity induced by aluminum chloride in rats.

Human exposure to aluminum is inevitable, and one of the most adverse health effects of aluminum is a decrease in male fertility rates. Therefore, this study investigated the ameliorative effects of an aqueous extract from Laurus nobilis-bay leaf (BL) on aluminum chloride (AlCl3)-induced testicular toxicity in rats. Twenty-four Wistar rats were divided into four groups (n = 6, each group): The control (group 1) received normal saline; Group 2 animals were intraperitoneally administered with 30 mg/kg body weight (BW) AlCl3; and Groups 3 and 4 were co-administered AlCl3 with 125 or 250 mg/kg BW of BL extract, respectively, for 21 days. Testes, epididymis, and blood samples were collected. Testicular plasma enzyme activity was measured using a spectrophotometric assay, while concentrations of inflammatory biomarkers were determined using enzyme-linked immunosorbent assay kits. There was a significant increase (p < 0.05) in testicular enzyme activity in the group treated with AlCl3. However, there was no significant (p > 0.05) difference in testicular enzyme activity in groups co-administered AlCl3 and BL extract as compared with that in control. There was a significant (p < 0.05) increase in testicular nitrite concentration in the AlCl3-treated group, whereas the administration of BL extract significantly (p < 0.05) decreased nitrite concentration in Groups 3 and 4. Furthermore, the administration of BL extracts increased sperm count and improved the morphology of the testes in AlCl3-treated rats. Flavonoids, phenolic compounds, alkaloids, tannin, glycosides, saponin, anthraquinones, and steroids were identified in BL extract, with alkaloids and glycosides being the most abundant. Aqueous extract from BL ameliorated the toxic effect of AlCl3 and exhibited anti-inflammatory properties by inhibiting nitrite production while improving sperm count and morphology in AlCl3-treated rats. The bioactivity of the extract may be attributed to the presence of a wide range of phytochemicals. Therefore, BL aqueous extract could be a promising source of novel compounds with male fertility-promoting and anti-inflammatory properties.

Hereditary angioedema is associated with an increased risk of venous thromboembolism

Hereditary angioedema is associated with an increased risk of venous thromboembolism

Influences of naringin supplementation on ruminal fermentation, inflammatory response, antioxidant capacity and bacterial community in high-concentrate diet of fattening goats

The objective of this study was to evaluate the effects of dietary naringin supplementation on rumen fermentation, inflammatory response and bacterial communities in fattening goats fed high-concentrate diet. Twenty four Boer male goats were randomly divided into three groups and assigned to receive dietary treatments. The three dietary treatments were a normal diet, a high-concentrate diet and a high-concentrate diet supplemented with 500 mg of naringin/kg of dry matter intake. Rumen fluid and plasma samples were collected at the end of the animal trial. Rumen fluid were analysed for pH, short-chain fatty acids, endotoxin (lipopolysaccharide, LPS) and microbiota. Illumina Miseq sequencing of the 16S rRNA gene was applied to investigate ruminal bacterial communities. The concentrations of interleukin −6 and tumour necrosis factor alpha as well as LPS-binding protein, haptoglobin, serum amyloid A and the activities of antioxdant enzymes in plasma were analysed. The result showed that feeding the high concentrate diet shifted the ruminal fermentation pattern from acetate towards propionate and valerate, and improved growth performance compared with the control group. However, the high concentrate diet promoted ruminal pH reduction and LPS release, modified bacterial communities and increased systemic inflammatory response. Naringin supplementation increased molar proportions butyrate and decreased valerate. Naringin supplementation decreased inflammatory response and increased the activities of antioxdant enzymes in plasma. Moreover, naringin addition increased the relative abundance of Bacteroidetes at the phylum level and Rikenellaceae_RC9_gut_group at the genus level. Taken together, these results suggest that dietary supplementation with naringin attenuates high grain diet-induced inflammatory response and modifies ruminal fermentation. HIGHLIGHTS Dietary supplementation of naringin decreased inflammatory response and increased the activities of antioxdant enzymes in fattening goats. Naringin supplementation changed ruminal microbiota of fattening goats. Naringin has potential for use as feed additive to modify ruminal fermentation in a high-grain intensive ruminant production.