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Compartmentalization of metabolic enzymes through protein–protein interactions is an emerging mechanism for localizing and regulating metabolic activity. Self-assembly into linear filaments is a common strategy for cellular compartmentalization of enzymes. Polymerization is often driven by changes in the metabolic state of the cell, suggesting that it is a strategy for shifting metabolic flux in response to cellular demand. Although polymerization of metabolic enzymes is widespread, observed from bacteria to humans, we are just beginning to appreciate their role in regulating cellular metabolism. In most cases, one functional role of metabolic enzyme filaments is allosteric control of enzyme activity. Here, we highlight recent findings, providing insight into the structural and functional significance of filamentation of metabolic enzymes in cells. [ABSTRACT FROM AUTHOR]

Meat color is a major quality attribute that influences the purchasing decisions of consumers at the point of sale. The stability of meat color gradually decreases after slaughter which then eventually leads to the discoloration. The discoloration will result in lost value during retail display. So, the mechanism behind slaughtering meat color variation is always a hot topic in the field of meat science which has been widely studied in order to improve meat color stability. Many factors from both preharvest and postharvest can influence the color stability, including pH value, temperature, different muscle, package, lipid oxidation, processing and so on. However, in this complex system, the inherent factors that determine meat color include the microstructure changes and biochemical functions. The structural protein determines the micro spatial structure of muscle, which affects the meat color from the aspects of water holding capacity, light scattering, and projection, etc. Enzymes and chaperones in sarcoplasmic protein mainly represent meat color by maintaining intracellular homeostasis, and regulate metabolism and myoglobin status. So far, the effects of many factors on meat color have been described in detail, and the role of myoglobin in meat color has been much clear. However, the appearance of meat color is a complex biochemical system, and there are still many unknowns to be explored. What happens to myoglobin and other functional proteins in this complex system remains unknown. Recently, many protein markers have been found in the application of proteomics in meat color research, and the pathways related to these biomarkers have been highlighted. However, that is still far from enough to clearly understand the variable color changes. The complex interaction between myoglobin and other functional proteins or enzymes are not fully understood. Therefore, the present article reviews the major achievements of recent proteomic researches on meat color of the biological functions and further summarized the potential mechanism of fresh meat discoloration. The differential proteins related to meat color were mainly analyzed. These differential proteins mainly include actin, myosin and titin in structural proteins, as well as chaperone proteins, heat shock proteins, metabolic enzymes and oxidoreductases in sarcoplasmic proteins. Effects of these proteins on meat color and its possible regulatory mechanisms were analyzed. The effects of structural protein abundance differences on light transmittance, absorption and scattering are reviewed from a physical point, and finally lead to the color changes. The difference proteins in sarcoplasmic proteins were reviewed from the perspective of biochemistry. Chaperones can maintain the stability of protein and slow down the denaturation of protein, thus helping to maintain the stability of meat color. Metabolic enzymes mainly affect a* value and metmyoglobin reductase activity. But due to different treatments in previous studies, the results of some metabolic enzymes have not reached a consistent conclusion. Further work still needs to be done to get the final conclusion. Oxidoreductases can maintain the stability of redox state in cells, and then benefit to maintain the color stability. Peroxidase can inhibit lipid oxidation and then help maintain color stability. It suggests that in future, protein biomarkers may be used to explain and predict meat color development. In this research, the mechanism of meat color improvement and the regulation of biomarkers were proposed. [ABSTRACT FROM AUTHOR]

The application of mass spectrometry imaging (MSI) for the study of spatiotemporal alterations of the metabolites in tumors has brought a number of significant biological results. At present, metabolite profiling based on MSI is typically performed on frozen tissue sections; however, the majority of clinical specimens need to be fixed in tissue fixative to avoid autolysis and to preserve antigenicity. In this study, we present the global impacts of different fixatives on the MS imaging of gastric cancer tissue metabolites. The MSI performances of 17 kinds of metabolites, such as amino acids, polyamines, cholines, organic acids, polypeptides, nucleotides, nucleosides, nitrogen bases, cholesterols, fatty acids, and phospholipids, in untreated, 10% formalin–, 4% paraformaldehyde–, acetone-, and 95% ethanol–fixed gastric cancer tissues were thoroughly explored for the first time. Furthermore, we also investigated the spatial expressions of 6 metabolic enzymes, namely, GLS, FASN, CHKA, PLD2, cPLA2, and EGFR, closely related to tumor-associated metabolites. Immunohistochemical staining carried out on the same tissue sections‚ which have undergone MSI analysis‚ suggests that enzymatic characterization is feasible after metabolite imaging. Combining the spatial signatures of metabolites and pathway-related metabolic enzymes in heterogeneous tumor tissues offers an insight to understand the complex tumor metabolism. [ABSTRACT FROM AUTHOR]

The bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) is a mitochondrial one-carbon folate metabolic enzyme whose role in cancer was not known until recently. MTHFD2 is highly expressed in embryos and a wide range of tumors but has low or absent expression in most adult differentiated tissues. Elevated MTHFD2 expression is associated with poor prognosis in both hematological and solid malignancy. Its depletion leads to suppression of multiple malignant phenotypes including proliferation, invasion, migration, and induction of cancer cell death. The non-metabolic functions of this enzyme, especially in cancers, have thus generated considerable research interests. This review summarizes current knowledge on both the metabolic functions and non-enzymatic roles of MTHFD2. Its expression, potential functions, and regulatory mechanism in cancers are highlighted. The development of MTHFD2 inhibitors and their implications in pre-clinical models are also discussed. [ABSTRACT FROM AUTHOR]

Therapeutic treatment of cocaine toxicity or addiction is a grand medical challenge. As a promising therapeutic strategy for treatment of cocaine toxicity and addiction to develop a highly efficient cocaine hydrolase (CocH) capable of accelerating cocaine metabolism to produce physiologically/biologically inactive metabolites, our previously designed A199S/S287G/A328W/Y332G mutant of human butyrylcholinesterase (BChE), known as cocaine hydrolase-1 (CocH1), possesses the desirably high catalytic activity against cocaine. The C-terminus of CocH1, truncated after amino acid #529, was fused to human serum albumin (HSA) to extend the biological half-life. The C-terminal HSA-fused CocH1 (CocH1-HSA), known as Albu-CocH1, Albu-CocH, AlbuBChE, Albu-BChE, or TV-1380 in literature, has shown favorable preclinical and clinical profiles. However, the actual therapeutic value of TV-1380 for cocaine addiction treatment is still limited by the short half-life. In this study, we designed and tested a new type of HSA-fused CocH1 proteins, i.e., N-terminal HSA-fused CocH1, with or without a linker between the HSA and CocH1 domains. It has been demonstrated that the catalytic activity of these new fusion proteins against cocaine is similar to that of TV-1380. However, HSA-CocH1 (without a linker) has a significantly longer biological half-life (t1/2 = 14 ± 2 h) compared to the corresponding C-terminal HSA-fused CocH1, i.e., CocH1-HSA (TV-1380 with t1/2 = 5–8 h), in rats. Further, the N-terminal HSA-fused CocH1 proteins with a linker have further prolonged biological half-lives: t1/2 = 17 ± 2 h for both HSA-EAAAK-CocH1 and HSA-PAPAP-CocH1, and t1/2 = 18 ± 3 h for HSA-(PAPAP)2-CocH1. These N-terminal HSA-fused CocH1 proteins may serve as more promising protein drug candidates for cocaine addiction treatment. [ABSTRACT FROM AUTHOR]

One-carbon metabolism is a universal metabolic process that mediates the transfer of one-carbon units for purine and thymidine synthesis. One-carbon metabolism has been found to be dysregulated in various cancer types due to its role in production of purine and pyrimidine nucleotides, epigenetic program, and redox homeostasis. One-carbon metabolism is composed a network of one-carbon metabolic enzymes. Disturbing the expression and enzymatic activity of these one-carbon metabolic enzymes could lead to fluctuations of metabolites in the tumor microenvironment. Serine hydroxymethyltransferases (SHMTs) and methylenetetrahydrofolate dehydrogenases (MTHFDs) are gradually recognized as important one-carbon metabolic enzymes for regulating tumor initiation and development, representing potential therapeutic targets for anti-tumor strategies. In the review, we primarily focused on the role of SHMTs and MTHFDs in cancer. Several inhibitors targeting MTHFDs and SHMTs have exert its potential to decrease tumor burden and inhibit tumor proliferation, highlighting the potential of targeting one-carbon metabolic enzymes for anti-cancer strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang and Wang.)

The mass balance, pharmacokinetics and metabolism of rovatirelin were characterised in healthy male subjects after a single oral dose of [14C]rovatirelin. [14C]Rovatirelin was steadily absorbed, and the peak concentrations of radioactivity and rovatirelin were observed in plasma at 5–6 h after administration. The AUCinf of radioactivity was 4.9-fold greater than that of rovatirelin. Rovatirelin and its metabolite (thiazoylalanyl)methylpyrrolidine (TAMP) circulated in plasma as the major components. The total radioactivity recovered in urine and faeces was 89.0% of the administered dose. The principal route of elimination was excretion into faeces (50.1% of the dose), and urinary excretion was the secondary route (36.8%). Rovatirelin was extensively metabolised to 20 metabolites, and TAMP was identified as the major metabolite in plasma and excreta among its metabolites. To identify the metabolic enzymes responsible for TAMP formation, the in vitro activity was determined in human liver microsomes. The enzymatic activity depended on NADPH, and it was inhibited by ketoconazole. Furthermore, recombinant human cytochrome P450 (CYP) 3A4 and CYP3A5 displayed enzymatic activity in the assay. Therefore, CYP3A4/5 are the most important enzymes responsible for TAMP formation. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase is a heterotetrameric complex comprising four nuclear-encoded subunits, catalyzes the oxidation of succinate to fumarate in the tricarboxylic acid cycle. A subset of cancers have been found to be associated with mutations in the four SDH genes. However, the functional roles of the SDH complex in tumorigenesis remain largely unclear, especially in hepatocellular carcinoma (HCC). Here, we investigated the expression levels of the four SDH subunits and their clinical significance in HCC, followed by systematic exploration of the effects of SDH dysfunction on HCC cell survival and metastasis both in vitro and in vivo, as well as the underlying molecular mechanisms. Our results showed that the expression of the SDHA/B/C/D subunits was significantly downregulated in HCC, associated with poor patient prognosis, and contributed to SDH inactivation. Additionally, attenuated SDH activity following SDHC knockdown promoted HCC-cell growth and metastasis both in vitro and in vivo via elevated reactive oxygen species levels and subsequent activation of nuclear factor-κB signaling. These findings suggest a critical tumor-suppressive role for SDH and provide strong evidence supporting this enzyme as a potential drug target in the treatment of HCC. [ABSTRACT FROM AUTHOR]

In presented study, in vivo effects of the important polyphenol ellagic acid and CCl4 compound known for its toxic effects on metabolic activity levels of some rat erythrocyte enzymes such as G6PD (glucose 6-phosphate dehydrogenase), 6PGD (6-phosphogluconate dehydrogenase), GR (Glutathione reductase), TrxR (Thioredoxin reductase) and GST (Glutathione S-transferase) were investigated. G6PD enzyme activity meaning rised in CCl4 group and ellagic acid+CCl4 group compared to the control group (p<0.001). 6PGD enzyme activity decreased in CCl4 applied group compared to control group (p<0.05). The enzyme activity level increased in ellagic acid (p<0.05) and CCl4+ellagic acid (p<0.01) applied groups. An increase was observed in ellagic acid (p<0.001) and CCl4+ellagic acid (p<0.001) applied groups compared to CCl4 administered group. GST enzyme activity reduced in CCl4 applied group compared to control group (p<0.01). GR enzyme activity decreased significantly in CCl4 and ellagic acid groups compared to control group (p<0.05 and p<0.01). TrxR enzyme activity decreased in CCl4 group and ellagic acid administered group compared to control group (p<0.001). A decrease in CCl4+ellagic acid group compared to control was also observed (p<0,001). [ABSTRACT FROM AUTHOR]

• Disulfiram exhibits concentration-dependent bactericidal activity against Staphylococcus aureus. • Disulfiram has potent in-vivo activity in a murine neutropenic thigh infection model, comparable with vancomycin. Antimicrobial resistance is an urgent threat affecting healthcare systems worldwide. Identification of novel molecules capable of escaping current resistance mechanisms and exhibiting potent activity against highly drug-resistant strains is the unmet need of the hour. Whole cell growth inhibition assays were used to screen and identify novel inhibitors. The hit compounds were tested against Vero cells to determine the selectivity index, followed by time-kill kinetics against Staphylococcus aureus. The ability of disulfiram to synergize with several approved drugs utilized for the treatment of S. aureus was determined using fractional inhibitory concentration indexes, followed by its ability to decimate staphyloccocal infections ex vivo. Finally, the in-vivo potential of disulfiram was determined in a neutropenic murine model of S. aureus infection. The screening showed that disulfiram has equipotent antibacterial activity against S. aureus , including clinical drug-resistant strains (minimum inhibitory concentration 8–16 mg/L). Disulfiram exhibited concentration-dependent bactericidal activity (∼7 log 10 colony-forming units/mL reduction), synergized with linezolid and gentamycin against S. aureus, eradicated staphylococcal biofilms (64-fold better than vancomycin), decimated intracellular S. aureus better than vancomycin, exhibited longer post antibiotic effect than vancomycin, and reduced bacterial counts in murine thigh as well as vancomycin at 50 mg/kg. Taken together, disulfiram exhibits all the characteristics required for repurposing as an antibacterial targeting staphylococcal infections. [ABSTRACT FROM AUTHOR]

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This study investigates the biodegradation of crude oil by a mixed culture of bacteria isolated from the Qinghai-Tibet plateau using gas chromatography-mass spectrometer (GC-MS) and the gravimetric method. The results showed that a mixed culture has a stronger ability to degrade hydrocarbon than pure cultures. Once both Nocardia soli Y48 and Rhodococcus erythropolis YF28-1 (8) were present in a culture, the culture demonstrated the highest crude oil removal efficiency of almost 100% after 10 days of incubation at 20 °C. Moreover, further analysis of the degradation mechanisms used by the above strains, which revealed utilization of different n-alkane substrates, indicated the diversity of evolution and variations in different strains, as well as the importance of multiple metabolic mechanisms for alkane degradation. Therefore, it is concluded that a mixed culture of Y48 and YF28-1 (8) strains can provide a more effective method for bioremediation of hydrocarbon-contaminated soil in permafrost regions. [ABSTRACT FROM AUTHOR]

Cyanobacteria possess an atypical tricarboxylic acid (TCA) cycle with various bypasses. Previous studies have suggested that a cyclic flow through the TCA cycle is not essential for cyanobacteria under normal growth conditions. The cyanobacterial TCA cycle is, thus, different from that in other bacteria, and the biochemical properties of enzymes in this TCA cycle are less understood. In this study, we reveal the biochemical characteristics of malate dehydrogenase (MDH) from Synechocystis sp. PCC 6803 MDH (SyMDH). The optimal temperature of SyMDH activity was 45–50°C and SyMDH was more thermostable than MDHs from other mesophilic microorganisms. The optimal pH of SyMDH varied with the direction of the reaction: pH 8.0 for the oxidative reaction and pH 6.5 for the reductive reaction. The reductive reaction catalysed by SyMDH was activated by magnesium ions and fumarate, indicating that SyMDH is regulated by a positive feedback mechanism. The Km-value of SyMDH for malate was approximately 210-fold higher than that for oxaloacetate and the Km-value for NAD+ was approximately 19-fold higher than that for NADH. The catalytic efficiency of SyMDH for the reductive reaction, deduced from kcat-values, was also higher than that for the oxidative reaction. These results indicate that SyMDH is more efficient in the reductive reaction in the TCA cycle, and it plays key roles in determining the direction of the TCA cycle in this cyanobacterium.

Abstract: This study was conducted to estimate the effects of dietary protein and lipid levels on the growth, body composition, gonadal development and activity of liver metabolic enzymes of the brown trout Salmo trutta fario broodstock. Ten diets were formulated containing five different protein levels (360, 390, 420, 450 and 480 g/kg) and two different lipid levels (90 and 180 g/kg). The experiment was a completely randomized 5 × 2 factorial design. The fish with an initial body weight of 462.53 ± 45.40 g were cultured in a spring water flow‐through system for 77 days. The growth performance was affected by dietary protein and lipid levels. Increase in the dietary protein and lipid resulted in increase in the body lipid and protein contents. The male gonadosomatic index decreased in the groups treated with relatively high levels of protein (390–480 g/kg). The activities of the hepatic amino acid‐catabolizing enzymes—alanine aminotransferase and aspartate aminotransferase—increased significantly with the increase in the dietary protein level. The activities of the lipogenic enzymes (fatty acid synthetase and glucose‐6‐phosphate dehydrogenase) and gluconeogenic enzyme (fructose‐1,6‐bisphosphatase) increased with the increase in the dietary protein level. Further, an increase in the activities of glycolytic enzyme in liver with an increase in the dietary lipid was observed. The variation in some intermediary metabolizing enzymes due to dietary components supports the high‐metabolic adaptability of this species to dietary protein and lipid levels. A diet with 450 g/kg protein and 90 g/kg lipid with 24.56 mg/kJ protein/energy ratio maximizes the growth, feed efficiency and gonadal development. [ABSTRACT FROM AUTHOR]

A study was conducted to assess the adaptive capability of three indigenous goat breeds to heat stress. Thirty six 10 months to one-year-old female goats of Osmanabadi, Malabari and Salem Black breeds were randomly divided into six groups, OC (n = 6; Osmanabadi control), OHS (n = 6; Osmanabadi heat stress), MC (n = 6; Malabari control), MHS (n = 6; Malabari heat stress), SBC (n = 6; Salem Black control) and SBHS (n = 6; Salem Black heat stress). Among the metabolic activity controlling hormones, the breed factor significantly (P < 0.05) influenced only plasma triiodothyronine (T3). However, heat stress significantly (P < 0.05) decreased thyroid stimulating hormone (TSH) in both MHS and SHS groups while significantly (P < 0.05) decreased the plasma T3 in MHS. The rumen metabolites such as acetate, propionate, butyrate and total volatile fatty acids (TVFAs) showed significant (P < 0.05) variation for both breed and treatment effect. The Salem Black breed did not show any significant variation for most of the rumen metabolites as compared to both Osmanabadi and Malabari breeds for the heat stress treatment. The study indicated the importance of the metabolic alterations in indigenous goat breeds to cope to the seasonal rhythms. The results indicated that on comparative basis, Salem Black breed adapted better to the heat stress challenges. [ABSTRACT FROM AUTHOR]

Drug metabolism plays vital roles in the absorption and pharmacological activity of poorly soluble natural medicines. It is important to choose suitable delivery systems to increase the bioavailability and bioactivity of natural medicines with low solubility by regulating their metabolism and pharmacokinetics. This review investigates recent developments about the metabolic and pharmacokinetic behavior of poorly soluble natural medicines and their delivery systems. Delivery systems, dosage, administration route and drug-drug interactions alter the metabolic pathway, and bioavailability of low-solubility natural medicines to different degrees. Influencing factors such as formulation, dosage, and administration route are discussed. The metabolic reactions, metabolic enzymes, metabolites and pharmacokinetic behaviors of low-solubility natural medicines, and their delivery systems are systematically reviewed. There are various metabolic situations in the case of low-solubility natural medicines. CYP3A4 and CYP2C are the most common metabolic enzymes, and hydroxylation is the most common metabolic reaction of low solubility natural medicines. The stereo isomeric configuration can have a large influence on metabolism. This review will be useful for physicians and pharmacists to guide more accurate treatment with low-solubility natural medicines by increasing drug efficacies and protecting patients from toxic side effects. [ABSTRACT FROM AUTHOR]

Carbohydrate metabolism and the antioxidant defence system of heart and muscle of the Antarctic notothenioids Notothenia rossii and Notothenia coriiceps were evaluated in response to heat stress (8 °C) over 144 h. N. rossii heart exhibited decreased glycolysis and aerobic metabolism after up to 12 h of exposure to 8 °C, and anaerobiosis was inhibited within 24 h. However, these pathways were stimulated after 72 h at 8 °C. The consumption of glucose-6-phosphate, derived from hexokinase (HK), by glucose-6-phosphate dehydrogenase (G6PDH) decreased in N. rossii heart within 6 h at 8 °C, with a subsequent increase at 72 h. In N. rossii muscle at 8 °C, glycolysis was stimulated within 2 h by an increase in pyruvate kinase (PK), and aerobic metabolism was stimulated at 144 h, together with anaerobiosis. In N. coriiceps heart at 8 °C, glucose break down by HK decreased within 2 h and subsequently increased at 12 and 24 h. Increased glucose-6-phosphate consumption by G6PDH occurred within 6 h at 8 °C. In N. coriiceps muscle at 8 °C, glycolysis was stimulated at 2 and 6 h, with subsequent inhibition within 24 h, as indicated by HK activity. Aerobic metabolism was inhibited at 72 and 144 h at 8 °C through the inhibition of citrate synthase (CS). Heat stress caused responses were only occasional and transient in antioxidant defence system of both species in the heart and muscle, leading to increased glutathione (GSH) and decreased levels of lipoperoxidation in the heart of both species. The results obtained in this study in the heart and muscles indicate that under heat stress at 8 °C, N. rossii is more responsive than N. coriiceps with respect to carbohydrate metabolism. [ABSTRACT FROM AUTHOR]

A 60-day feeding trial was conducted with different inclusion levels of de-oiled rice bran (DORB) to study the digestive enzyme activity, physio-metabolic changes and oxidative stress in Labeo rohita fingerlings. Six iso-nitrogenous (30% crude protein), iso-lipidic (6% crude lipid) and iso-energetic (380.14 Kcal/100 g) semi-purified diets were prepared with the graded levels of DORB viz. 0 (control), T20 (20%), T30 (30%), T40 (40%), T50 (50%) and T60 (60%). Three hundred and fifteen (315) fingerlings with an average weight of 8 ± 0.5 g were distributed randomly in seven treatments in triplicates, following a completely randomised design (CRD). The digestive enzyme, protease and amylase activities were higher in 20, 30 and 40% DORB fed groups but the Lipase activity did not vary significantly whereas, SOD and GST activity was significantly lower (p < 0.05) in the same groups. The T50 and T60 groups showed significantly higher (p < 0.05) hepatic LDH (Lactate dehydrogenase), GST (Glutathione-s-transferase) and SOD activity, while RBC (Red blood cell) and WBC (White blood cell) content were found significantly lower in these groups. The catalase activity did not vary significantly (p > 0.05) among treatment group. Serum glucose content was higher in the T40, T50 and T60 groups, while serum total protein, albumin, NBT (Nitroblue tetrazolium) and haemoglobin levels were not significantly different among the treatments. From the study, it can be concluded that DORB causes stress to fish when fed at higher inclusion level (50 & 60%). [ABSTRACT FROM AUTHOR]

Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters) were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor. [ABSTRACT FROM AUTHOR]

(Pre-partum supplementation of heit-chrose on post-partum blood profile and recovery of body weight of dairy cows) ABSTRACT. This study aimed to determine the profile of blood, metabolic enzymes and recovery of body weight in dairy cows fed diet supplemented with Heit-CHrose (Feed supplement containing saponins, allicin, organic mineral: Se, Cr, and Zn). The experiments were conducted with 4 treatments, R0 : control diet (CP 13,79% and TDN 67,2%), R1 : R0 supplemented with organic minerals (Cr 1,5 ppm; Se 0,3 ppm; Zn-Lyzinat 40 ppm), R2 : Ro supplemented with Heit-CHrose are given in the component feeding, and R3 : Ro supplemented with Heit-CHrose are given in total mixed ration (TMR). Data were tested using analysis of variance with a completely randomized design using four replications, and HSD test. The results showed that the supplementation of Heit-CHrose to the diet of dairy cows gave significant effect (P 0.01) on blood glucose and recovery of body weight, but had no effect (P 0.05) on hemoglobin, blood urea nitrogen (BUN), total protein and blood cholesterol and metabolic enzyme (alkali phospatase). Supplementation of Heit Chrose in dairy cows diet with component feeding and TMR increases blood glucose and recovery of body weight.

A 60-day indoor experiment was conducted to study the effect of dietary supplementation of biofloc on metabolic enzyme activities and immune responses in Penaeus monodon juveniles. Biofloc developed in indoor fibreglass-reinforced plastic ( FRP) tanks (1000 L) was used as dietary supplement in P. monodon (2.90 ± 0.10 g) reared in 1000-L FRP tanks. Graded level of dried biofloc was included in shrimp basal diets, 0% (control, B0), 4% (B4), 8% (B8) and 12% (B12). The level of metabolic enzymes like malate dehydrogenase ( MDH), aspartate aminotransferase ( AST) and alanine aminotransferase ( ALT) was not significantly different with control up to 8% dietary supplementation. A higher level of total haemocyte count ( THC) was noticed in B8 (22.16 ± 2.17 × 106 cells mL−1) and B4 (21.11 ± 0.56 × 106 cells mL−1) compared with control, C (14.61 ± 2.74 × 106 cells mL−1). Biofloc-supplemented groups recorded significantly higher ( P < 0.05) serum SOD and catalase activity ( P < 0.01) in comparison with control. The groups fed with 4% dietary biofloc supplement recorded highest relative percentage survival ( RPS), 45% after challenge with Vibrio harveyi followed by 36% and 27% RPS in B8 and B12 groups. Based on these results, it can be concluded that supplementation of biofloc even at 4% level in the feed improves immune responses and metabolic activities in black tiger shrimp juveniles. [ABSTRACT FROM AUTHOR]

The nucleotide CTP can be synthesized de novo from UTP via the metabolic enzyme CTP synthase (CTPS). As a textbook enzyme, CTPS has been extensively studied for seven decades. However, it came as a surprise when CTPS was found to form snake-shaped mesoscale cytoophidia in fruit fly cells. Since 2010, more and more studies have demonstrated that CTPS can form cytoophidia within the cells across all three domains of life. Oligomers of CTPS form filaments that are undetectable under light microscopy. This review summarizes our current understanding of cytoophidia and filaments, highlighting some basic features such as conservation, morphology and functions of the two levels of CTPS structures., (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Environmental pollutants can disrupt the homeostasis of endogenous metabolites in organisms, leading to metabolic disorders and syndromes. However, it remains highly challenging to efficiently screen for critical biological molecules affected by environmental pollutants. Herein, we found that enzyme could catalyze hydrogen-deuterium (H-D) exchange between a deuterium-labeled environmental pollutant [D 38 -bis(2-ethylhexyl) phthalate (D 38 -DEHP)] and several groups of enzyme-regulated metabolites [cardiolipins (CLs), monolysocardiolipins (MLCLs), phospholipids (PLs), and lysophospholipids (LPLs)]. A high-throughput scanning identified the D-labeled endogenous metabolites in a simple enzyme [phospholipase A 2 (PLA 2 )], enzyme mixtures (liver microsomes), and living organisms (zebrafish embryos) exposed to D 38 -DEHP. Mass fragmentation and structural analyses showed that similar positions were D-labeled in the CLs, MLCLs, PLs, and LPLs, and this labeling was not attributable to natural metabolic transformations of D 38 -DEHP or incorporation of its D-labeled side chains. Molecular docking and competitive binding analyses revealed that DEHP competed with D-labeled lipids for binding to the active site of PLA 2 , and this process mediated H-D exchange. Moreover, competitive binding of DEHP against biotransformation enzymes could interfere with catabolic or anabolic lipid metabolism and thereby affect the concentrations of endogenous metabolites. Our findings provide a tool for discovering more molecular targets that complement the known toxic endpoints of metabolic disruptors.

The nutritional potential of protein isolate from rubber seed (RPI) in the diets of Labeo rohita (initial average weight 4.45 ± 0.01 g) was assessed in a 60 days feeding trial. Five isonitrogenous (32.62 ± 0.13 CP Kg −1 ) and isocaloric (18.47 ± 0.08 MJ kg −1 ) experimental diets were formulated with graded level of RPI like 0%, 25%, 50%, 75%, or 100% in replacement for soybean protein isolate (SPI), and designated as Control, RPI25, RPI50, RPI75, RPI100, respectively. The RPI contributed 0%, 13%, 26%, 39% or 52% of the total dietary protein in the diets. Each diets were randomly assigned to 15 experimental tanks containing 12 fish in triplicates and fed to satiation twice daily at 10:00 h and 18:00 h. At the end of the feeding trial, the growth performance and nutrient utilization indices such as percent weight gain (WG%), specific growth rate (SGR), daily growth coefficient (DGC), feed intake (FI), protein efficiency ratio (PER), feed conversion ratio (FCR) and protein retention (PR) values were not significantly (p > 0.05) affected by the dietary treatments irrespective of inclusion levels of RPI. A significantly higher (p < 0.05) hepatosomatic index (HSI) was recorded in the control and RPI 50 group compared to other treatment groups (p < 0.05). The intestinal somatic index (ISI) and Survival rate were similar (p > 0.05) in all the groups. The apparent digestibility coefficients (ADCs) of dry matter and protein for fish fed the control and RPI 100 diets were found to be similar, while RPI 50 and RPI 75 groups exhibited a significantly lower value corresponding to the protease enzyme activity. The whole body compositions and digestive/metabolic enzymes activities among the various groups did not differ significantly (p > 0.05). The serum cholesterol and triglyceride levels were found to be significantly higher (p < 0.05) in the control compared to the RPI fed groups. Significantly higher serum glucose level was recorded in RPI 50, while a reverse was seen in the liver glycogen contents. Overall, this study clearly showed that RPI from rubber seed can serve as alternative protein source in the diets of L. rohita fingerlings without any adverse effects on growth, nutrient utilization and physio-metabolic responses. [ABSTRACT FROM AUTHOR]

Contexts:Exposure to environmental pollutants such as carbon tetrachloride (CCl4) causes liver injuries. There are claims that extracts fromSyzygium aromaticum(Linn.) Merrill & L.M.Perry, (Myrtaceae) protects from such injuries. Objective:This study investigates the protective effects of cold-pressedS. aromaticumoil (CO) against CCl4-induced liver toxicity in rats. Materials and methods:CO was orally administered to rats in two doses (100 and 200 mg/kg) along with CCl4(1 mL/kg in olive oil) for 8 weeks. Indices of liver and kidney functions, lipid profile, and peroxidation were evaluated in rats’ serum and tissues. Fatty acids and bioactive lipids of CO were analyzed. Results:High levels of monounsaturated fatty acids (39.7%) and polyunsaturated fatty acids (42.1%) were detected in CO. The oil contained high amounts of tocols and phenolics. The LD50value at 24 h was approximately 5950 mg/kg. Treatment with 200 mg/kg CO resulted in a decrease of creatinine, urea, and uric acid levels to 0.86, 32.6, and 2.99 mg/dL, respectively. Levels of TL, TC, TAG, LDL-C, and VLDL-C were decreased to 167, 195.3, 584.5, 74.6, and 39.0 mg/L, respectively, after 8 weeks of treatment. Hepatic malondialdehyde levels were reduced and glutathione levels were elevated in CO-treated rats. CO reduced the activities of AST, ALT, and ALP as well as kidney function markers, protein, and lipid profiles, respectively. Histopathological examination of liver indicated that CO treatment reduced fatty degenerations, cytoplasmic vacuolization, and necrosis. Conclusion:CO possessed a protective effect against CCl4-induced hepatotoxicity in rats, mediated possibly by the antioxidant properties of the oil. [ABSTRACT FROM AUTHOR]

Accumulating evidence from the last decade has shown that many pharmaceutical excipients are not pharmacologically inert but instead have effects on metabolic enzymes and/or drug transporters. Hence, the absorption, distribution, metabolism, and elimination (ADME) of active pharmaceutical ingredients (APIs) may be altered due to the modulation of their metabolism and transport by excipients. The impact of excipients is a potential concern for Biopharmaceutics Classification System (BCS)-based biowaivers, particularly as the BCS-based biowaivers have been extended to class 3 drugs in certain dosage forms. The presence of different excipients or varying amounts of excipients between formulations may result in bio-inequivalence. The excipient impact may lead to significant variations in clinical outcomes as well. The aim of this paper is to review the recent findings of excipient effects on gastrointestinal (GI) absorption, focusing on their interactions with the metabolic enzymes and transporters in the GI tract. A wide range of commonly used excipients such as binders, diluents, fillers, solvents, and surfactants are discussed here. We summarized the reported effects of those excipients on GI tract phase I and phase II enzymes, uptake and efflux transporters, and relevant clinical significance. This information can enhance our understanding of excipient influence on drug absorption and is useful in designing pharmacokinetic studies and evaluating the resultant data. [ABSTRACT FROM AUTHOR]

The global atmospheric CO concentration is currently (2012) 393.1 μmol mol, an increase of approximately 42 % over pre-industrial levels. In order to understand the responses of metabolic enzymes to elevated CO concentrations, an experiment was conducted using the Free Air CO Enrichment (FACE )system. Two conventional japonica rice varieties ( Oryza sativa L. ssp. japonica) grown in North China, Songjing 9 and Daohuaxiang 2, were used in this study. The activities of ADPG pyrophosphorylase, soluble and granule-bound starch synthases, and soluble and granule-bound starch branching enzymes were measured in rice grains, and the effects of elevated CO on the amylose and protein contents of the grains were analyzed. The results showed that elevated CO levels significantly increased the activity of ADPG pyrophosphorylase at day 8, 24, and 40 after flower, with maximum increases of 56.67 % for Songjing 9 and 21.31 % for Daohuaxiang 2. Similarly, the activities of starch synthesis enzymes increased significantly from the day 24 after flower to the day 40 after flower, with maximum increases of 36.81 % for Songjing 9 and 66.67 % for Daohuaxiang 2 in soluble starch synthase (SSS), and 25.00 % for Songjing 9 and 36.44 % for Daohuaxiang 2 in granule-bound starch synthase (GBSS), respectively. The elevated CO concentration significantly increased the activity of soluble starch branching enzyme (SSBE) at day 16, 32, and 40 after flower, and also significantly increased the activity of granule-bound starch branching enzyme (GBSBE) at day 8, 32, and 40 after flower. The elevated CO concentration increased the peak values of enzyme activity, and the timing of the activity peaks for SSS and GBSBE were earlier in Songjing 9 than in Daohuaxiang 2. There were obvious differences in developmental stages between the two varieties of rice, which indicated that the elevated CO concentration increased enzyme activity expression and starch synthesis, affecting the final contents of starch and protein in the rice grains. Our results will provide a foundation for understanding the physiological mechanisms of rice yield under elevated atmospheric CO concentrations. [ABSTRACT FROM AUTHOR]

Longissimus dorsi muscles from 3 goat species were assigned to high and low drip loss groups. Physio-chemical properties, sarcomere length, and proteome profiles were investigated. The high drip loss group had lower pH, higher brightness, and higher shear force values, and shorter sarcomere lengths than the low drip loss group. 22 differential proteins were identified between high and low loss groups. α-Enolase, NADH dehydrogenase, pyruvate dehydrogenase E1, HSP27, superoxide dismutase, peroxiredoxin-2, myosin, and the myosin light chain were among these proteins, which were metabolic enzymes, stress response factors, and structural proteins that affected glycolysis, oxidation, and muscle contraction. Drip loss was probably produced via proteins involved in glycolysis, oxidation, and muscle contraction. [ABSTRACT FROM AUTHOR]

One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) forms filaments at low pH and that filament formation leads to enzymatic inactivation. Filament formation by Gln1 is a highly cooperative process, strongly dependent on macromolecular crowding, and involves back-to-back stacking of cylindrical homo-decamers into filaments that associate laterally to form higher order fibrils. Other metabolic enzymes also assemble into filaments at low pH. Hence, we propose that filament formation is a general mechanism to inactivate and store key metabolic enzymes during a state of advanced cellular starvation. These findings have broad implications for understanding the interplay between nutritional stress, the metabolism and the physical organization of a cell.

Drug therapy is the primary modality for depression; however, its outcome is often unpredictable, ranging from beneficial effects to serious adverse effects. Genetic variations in drug metabolizing enzymes and pharmacodynamic molecules are responsible for a considerable proportion of interindividual differences in the effectiveness and toxicity of antidepressants. For the improvement in the use of antidepressants, the focus is mainly on personalized treatment emphasizing interindividual differences in genes. This study provides a comprehensive review of the literature on the clinical applications of pharmacogenomics for antidepressant therapy. The polymorphisms of metabolizing enzymes ( CYP2D6, CYP2C19 , and others) governing the pharmacokinetic behavior of drugs are potential predictors of side effects or treatment failure with medications and there are good pharmacogenetic clinical recommendations for a wide selection of psychopharmacological agents based on functional diplotypes of CYP2C19 and CYP2D6 . The relationship between pharmacodynamic genes, including FKBP5, SLC6A4, BDNF, ABCB1, HTR1A , and HTR2A , and clinical outcomes varies in different races. Receptors that are currently used as drug targets for antidepressant drugs are evolutionarily conserved to a higher extent than genes encoding drug metabolism, and the actionability of pharmacodynamic-related genotyping is currently still questionable. The limited availability of largescale, long-term clinical studies on different races and medications currently impedes the implementation of pharmacogenomics in antidepressant treatment. The use of pharmacokinetic and pharmacodynamic modeling, and therapeutic drug monitoring combined with genetic, somatic, dietary, and environmental factors represents a promising avenue for improving the precision and effectiveness of antidepressant therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Yinzhihuang (YZH), a traditional Chinese medicine prescription, was widely used to treat cholestasis. Cholestatic liver injury limited the use of the immunosuppressive drug cyclosporine A (CsA) in preventing organ rejection after solid organ transplantation. Clinical evidences suggested that YZH could enhance bile acids and bilirubin clearance, providing a potential therapeutic strategy against CsA-induced cholestasis. Nevertheless, it remains unclear whether YZH can effectively alleviate CsA-induced cholestatic liver injury, as well as the molecular mechanisms responsible for its hepatoprotective effects. The purpose of the present study was to investigate the hepatoprotective effects of YZH on CsA-induced cholestatic liver injury and explore its molecular mechanisms in vivo and vitro. The results demonstrated that YZH significantly improved the CsA-induced cholestatic liver injury and reduced the level of liver function markers in serum of Sprague-Dawley (SD) rats. Targeted protein and gene analysis indicated that YZH increased bile acids and bilirubin efflux into bile through the regulation of multidrug resistance-associated protein 2 (Mrp2), bile salt export pump (Bsep), sodium taurocholate cotransporting polypeptide (Ntcp) and organic anion transporting polypeptide 2 (Oatp2) transport systems, as well as upstream nuclear receptors farnesoid X receptor (Fxr). Moreover, YZH modulated enzymes involved in bile acids synthesis and bilirubin metabolism including Cyp family 7 subfamily A member 1 (Cyp7a1) and uridine 5'-diphosphate (UDP) glucuronosyltransferase family 1 member A1 (Ugt1a1). Furthermore, the active components geniposidic acid, baicalin and chlorogenic acid exerted regulated metabolic enzymes and transporters in LO2 cells. In conclusion, YZH may prevent CsA-induced cholestasis by regulating the transport systems, metabolic enzymes, and upstream nuclear receptors Fxr to restore bile acid and bilirubin homeostasis. These findings highlight the potential of YZH as a therapeutic intervention for CsA-induced cholestasis and open avenues for further research into its clinical applications.

Antiretroviral therapy is the recognized treatment for human immunodeficiency virus (HIV) infection involving several antiviral agents. Even though highly active antiretroviral therapy has been proven to be very effective in suppressing HIV replication, the antiretroviral drugs, belonging to different pharmacological classes, present quite complex pharmacokinetic properties such as extensive drug metabolism and transport by membrane-associated drug carriers. Moreover, due to uncomplications or complications in HIV-infected populations, an antiretroviralbased multiple-drug coadministration therapy strategy is usually applied for treatment effect, thus raising the possibility of drug-drug interactions between antiretroviral drugs and common drugs such as opioids, stains, and hormonal contraceptives. Herein, thirteen classical antiretroviral drugs approved by US Food and Drug Administration were summarized. Besides, relative drug metabolism enzymes and transporters known to interact with those antiretroviral drugs were detailed and described. Furthermore, one after the summarized antiretroviral drugs, the drug-drug interactions between two antiretroviral drugs or antiretroviral drug - conventional medical drugs of the past decade were discussed and summarized. This review is intended to deepen the pharmacological understanding of antiretroviral drugs and promote more secure clinical applications for antiretroviral drugs to treat HIV., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Fine particulate matter (PM) exposure is associated with morbidity and mortality induced by respiratory diseases and increases the lung cancer risk. However, the mechanisms therein involved are not yet fully clarified. In this study, the PM suspensions at different dosages (0.375, 1.5, 6.0, and 24.0 mg/kg body weight) were respectively given to rats by the intratracheal instillation. The results showed that PM exposure induced inflammatory cell infiltration and hyperemia in the lung tissues and increased the inflammatory cell numbers in bronchoalveolar lavage fluid. Furthermore, PM significantly elevated the levels of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, and intercellular adhesion molecule 1 (ICAM-1) and the expression of c-fos and c-jun in rat lungs exposed to higher dose of PM. These changes were accompanied by decreases of activities of superoxide dismutase and increases of levels of malondialdehyde, inducible nitric oxide synthase, nitric oxide, cytochrome P450s, and glutathione S-transferase. The results implicated that acute exposure to PM induced pathologically pulmonary changes, unchained inflammatory and oxidative stress processes, activated metabolic enzyme activity, and enhanced proto-oncogene expression, which might be one of the possible mechanisms by which PM pollution induces lung injury and may be the important determinants for the susceptibility to respiratory diseases. [ABSTRACT FROM AUTHOR]

1. The human mass balance of14C-labelled ASP015K ([14C]ASP015K), an orally bioavailable Janus kinase (JAK) inhibitor, was characterized in six healthy male subjects after a single oral dose of [14C]ASP015K (100 mg, 3.7 MBq) in solution. [14C]ASP015K was rapidly absorbed with tmaxof 1.6 and 1.8 h for ASP015K and total radioactivity in plasma, respectively. Mean recovery in urine and feces amounted to 36.8% and 56.6% of the administered dose, respectively. The main components of radioactivity in plasma and urine were ASP015K and M2 (5′-O-sulfo ASP015K). In feces, ASP015K and M4 (7-N-methyl ASP015K) were the main components. 2. In vitrostudy of ASP015K metabolism showed that the major isozyme contributing to the formation of M2 was human sulfotransferase (SULT) 2A1 and of M4 was nicotinamideN-methyltransferase (NNMT). 3. Thein vitrointrinsic clearance (CLint_in vitro) of M4 formation from ASP015K in human liver cytosol (HLC) was 11-fold higher than that of M2. The competitive inhibitory effect of nicotinamide on M4 formation in the human liver was considered the reason for high CLint_in vitroof M4 formation, while each metabolic pathway made a near equal contribution to thein vivoelimination of ASP015K. ASP015K was cleared by multiple mechanisms. [ABSTRACT FROM AUTHOR]

A 60-day indoor trial was conducted to study the effect of periphyton supplementation on metabolic and immune responses in tiger shrimp, Penaeus monodon. Periphyton developed over bamboo substrate in outdoor tanks (15 m2) was used as dietary supplement for P. monodon (2.02 ± 0.04 g) reared in 1000 L FRP tanks. Graded levels of periphyton were included in shrimp basal diets: 0% (P0), 3% (P3), 6% (P6), 9% (P9) and P0 diet with natural periphyton ( NP) over bamboo substrate. At the end of the trial, P6 and NP showed significantly higher ( P < 0.01) growth rate, 23.9% and 20%, respectively, compared with control, P0. Comparatively, lower level of metabolic enzymes, such as lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and alanine aminotransferase, was recorded in treatments P3, P6 and NP compared with control, P0. The periphyton-supplemented group, P3 had significantly higher ( P < 0.05) superoxide dismutase (15.83 ± 0.96) and catalase activity (15.73 ± 0.69) compared to 6.88 ± 2.84 and 9.15 ± 0.67 unit mg−1 protein min−1, respectively, in P0. Similarly, higher total haemocyte counts, 32.58 ± 1.30, 28.51 ± 3.12 and 27.26 ± 4.43 × 106 cells mL−1, were recorded in P6, NP and P3, respectively, compared to P0, 23.57 ± 1.80 × 106 cells mL−1. After challenge with Vibrio harveyi, P3 recorded the highest relative percentage survival 67% followed by NP (58%) and P6 (42%) compared with control. However, treatment with highest periphyton inclusion (P9) did not differ significantly with P0 on growth and immunological parameters. This study indicates that periphyton supplementation at 3-6% level improves growth, immune response and metabolic activities in P. monodon. [ABSTRACT FROM AUTHOR]

The purpose of this work was to investigate the role of bioconjugation and carrier mediated efflux of conjugation products in the absorption mechanism of the sesquiterpene lactone nobilin in the Caco-2 model in vitro and to elucidate the impact of the extract of Chamomillae romanae flos and its ingredients on absorption. Transport experiments with inhibitors of P-gp, BCRP, and MRPs were performed to detect efflux and its connection to bioconversion and the effect of different ingredients of the plant extract on absorption processes was determined. Permeability, transport and bioconversion parameter values were deduced by kinetic multi-compartment modeling. Nobilin exhibited high permeability, low relative absorption and fast bioconversion producing glucuronide, cysteine conjugate, and glutathione conjugate that were transported by P-gp (the first two), apical MRP2 and basal MRP3 and possibly MRP1 out of the cell. Inhibition of efflux resulted in diminished bioconjugation and improved absorption. The extract increased the relative fraction absorbed primarily by directly inhibiting bioconversion, and by reducing efflux. Individual extract ingredients could only partly explain this effect. Extensive bioconversion, hence, limited absorption of nobilin in the Caco-2 model and the interplay between conjugation and efflux was shown to provide a possible mechanism for absorption increase. Plant extract increased absorption by this mechanism in addition to metabolic enzyme inhibition. [ABSTRACT FROM AUTHOR]

Cancers are characterized by aberrant cell signaling that results in accelerated proliferation, suppressed cell death, and reprogrammed metabolism to provide sufficient energy and intermediate metabolites for macromolecular biosynthesis. Here, we summarize the emerging “unconventional” roles of these regulators based on their newly identified interaction partners, different subcellular localizations, and/or structural variants. For example, the epidermal growth factor receptor (EGFR) regulates DNA synthesis, microRNA maturation and drug resistance by interacting with previously undescribed partners; cyclins and cyclin-dependent kinases (CDKs) crosstalk with multiple canonical pathways by phosphorylating novel substrates or by functioning as transcriptional factors; apoptosis executioners play extensive roles in necroptosis, autophagy, and in the self-renewal of stem cells; and various metabolic enzymes and their mutants control carcinogenesis independently of their enzymatic activity. These recent findings will supplement the systemic functional annotation of cancer regulators and provide new rationales for potential molecular targeted cancer treatments. [ABSTRACT FROM AUTHOR]

The effect of various dietary starch to proteins ratios ( STA/P) on growth performance, oxidative status and liver enzyme activities involved in intermediary metabolism in juvenile Nile tilapia was evaluated. Four isocaloric-practical diets (12.73 MJ kg−1 digestible energy) with increasing STA/ CP ratios were formulated. These were designated D0 (344 g crude protein ( CP) and 163.5 g starch ( STA) kg−1), D1 (310 g CP and 243 g STA kg−1), D2 (258 g CP and 322 g STA kg−1) and D3 (214 g CP and 401 g STA kg−1). Each diet was fed to triplicate groups of 60 fish (2.7 g) for 45 days. Compared with the control diet (D0), significantly ( P < 0.05) depressed growth and feed efficiency were observed only in the groups fed on diet D3. The activities of hepatic enzymes involved in glycolysis and lipogenesis pathways were significantly enhanced in groups fed on diet D3 compared with other diets. A significant ( P < 0.05) increase in catalase activity was detected only in groups fed on diet D3. Similarly, a significant ( P < 0.05) enhancement in superoxyde dismutase, glutathione S-transferases and glutathione peroxidise was observed in groups fed on diets D2 and D3 compared with other diets. Results demonstrate the ability of juvenile Nile tilapia to spare protein by dietary carbohydrate. [ABSTRACT FROM AUTHOR]

The effect of acute nitrite stress on gene expression of antioxidant enzymes, Hsp70 and metabolic enzymes in gill tissue of adult Procambarus clarkii (Girard, 1852) was evaluated. A 48 hours nitrite exposure was conducted, using four test concentrations (NO2-N = 1, 2, 3 and 4 mg l-1) plus a control group. Significantly increased mRNA expression was observed for all the antioxidant enzymes. A significant increase of Hsp70 mRNA expression was observed when exposed to 2 mg 1-1 nitrite-N at 12 h. An elevation in AST mRNA expression occurred in the 3 mg l-1 nitrite-N group at 12 h. No significant variation was observed for ALT. Elevations in SDH and Na+/K+-ATPase α-subunit mRNA expression were found throughout the experiment. This study shows that gene expression of antioxidant and metabolic enzymes could be helpful in predicting sublethal nitrite toxicity and it will also improve our understanding of the toxicological mechanisms of nitrite on crustacean. [ABSTRACT FROM AUTHOR]

Background: The Danning tablets (DNts) is commonly prescribed in China as a cholagogic formula. Our previous studies showed that DNts exerted the protective effect on α -naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis in a dose-dependent mannar. However, the detailed molecular mechanisms of DNts against ANIT-induced cholestasis are still not fully explored. Methods: Danning tablet (3 g/kg body weight/day) was adminis tered orally to experimental rats for seven days before they were treated with ANIT (60 mg/kg daily via g astrogavage) which caused cholestasis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (T-Bil), direct bilirubin (D-Bil) and total bile acid (TBA) were measured to evaluate th eprotectiveeffectofDanningtablet at 12, 24 and 48h after ANIT treatment. Meanwhile, total bi lirubin or total bile acid in the bile, urine and liver were also measured at 48h after ANIT treatment. Furthermore, the hepatic or renal mRNA and protein levels of metabolic enzymes and transports were investigated to e lucidate the protective mechanisms of Danning tablet against ANIT-induced cholestasis. Results: In this study, we found that DNts significantly attenuated tr anslocation of multidrug resi stance-associated protein 2 (Mrp2) from the canalicular membrane into an intracellular and up-regulated the hepatic mRNA and protein expressions of metabolic enzymes including cytochrome P450 2b1(Cyp2b1) and uridine diphosphate-5¢- glucuronosyltransferase (Ugt1a1)) and transporters including bile salt export pump (Bsep) and multidrug resistance protein 2 (Mdr2)) as well as renal organic solute transporter beta (Ost β ), accompanied by further increase in urinary and biliary excretion of bile acid and bilirubin. Conclusions: DNts might promote bile acid and bilirubin elimination by regulating the expressions of hepatic and renal transporters as well as hepatic metabolic enzymes. [ABSTRACT FROM AUTHOR]

We evaluated the effect of acute exposure to nitrite on expression of antioxidant and metabolic enzyme genes in gill tissue of advanced juvenile Cherax quadricarinatus. A 48h nitrite exposure was conducted, using four test concentrations (NO2–N=0.5, 1, 1.5 and 2mgL−1) plus a control group. The relative mRNA expression of mitochondrial manganese superoxide dismutase (mMnSOD), cytosolic MnSOD (cMnSOD), extracellular copper/zinc SOD (exCu/ZnSOD), catalase (CAT), glutathione S-transferase (GST), arginine kinase (AK), glutamate dehydrogenase (GDH), mitochondrial malate dehydrogenase (mMDH), Na+/K+-ATPase α-subunit and phosphoenolpyruvate carboxykinase (PEPCK) in gill tissue was measured. Significantly increased mRNA expression was observed for all the antioxidant enzymes after 12 and 24h. After 48h, they all decreased at high nitrite concentrations. The gene expression levels of AK, GDH, mMDH and Na+/K+-ATPase α-subunit showed similar trends as the antioxidant enzymes. Significant depression of gene expression levels of PEPCK occurred throughout the experimental time at high nitrite concentrations. The results indicated that nitrite could induce oxidative and metabolic stress in C. quadricarinatus, in a time dependent manner, which suggests they could be helpful in predicting sublethal nitrite toxicity and useful in environmental monitoring studies. [Copyright &y& Elsevier]

Context: Tarvada [ Cassia auriculata Linn. (Caesalpiniaceae)] is used against liver ailments in Indian folk medicine, but there is a lack of scientific evidence for this traditional claim. Objective: The present study investigated the protective effect of methanol extract of tarvada (MECA) roots on ethanol and antitubercular drug induced hepatotoxicity in rats. Materials and methods: In the therapeutic model, ethanol (40%, 4 g/kg b.w., p.o.) was administered to rats for 21 days and the intoxicated rats were treated with MECA (300 and 600 mg/kg, b.w.) and silymarin (100 mg/kg, b.w.) for next 7 days. In the prophylactic model, MECA and silymarin were administered simultaneously along with a combination of isoniazid (27 mg/kg, b.w.), rifampicin (54 mg/kg, b.w.) and pyrazinamide (135 mg/kg, b.w.) for 30 days. After the study duration, serum levels of AST, ALT, ALP, total bilirubin, total cholesterol, total protein, albumin were estimated along with hepatic catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and liver histopathology in each group. Results: Administration of tarvada root extract significantly ( p < 0.01 and p < 0.05) lowered the elevated levels of serum AST, ALT, ALP, total bilirubin, total cholesterol, total protein and restored the abnormal levels of enzymatic antioxidants and MDA in liver due to toxicant administration in a dose-dependent manner. These results were confirmed by histopathological analysis. Discussion and conclusion: Results suggest that tarvada root extract possess potent hepatoprotective activity against ethanol and antitubercular drug-induced hepatotoxicity in rats, which could be due to an inhibition of hepatic metabolizing enzymes and antioxidant activity. [ABSTRACT FROM AUTHOR]