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Data from in vitro studies are routinely used to estimate in vivo hepatic clearance of chemicals and this information is needed to parameterise physiologically based kinetic models. Such clearance data can be obtained from laboratory experiments using liver microsomes, hepatocytes, precision-cut liver slices or recombinant enzymes. Irrespective of the selected test system, scaling factors are required to convert the in vitro measured intrinsic clearance to a whole liver intrinsic clearance. Scaling factors such as the hepatic microsomal protein per gram of liver and/or the amount of cytochrome P450 per hepatocyte provide a means to calculate the whole liver intrinsic clearance. Here, a database from the peer-reviewed literature has been developed and provides quantitative metrics on microsomal protein (MP) and cytochrome P450 contents in vertebrate orders namely amphibians, mammals, birds, fish and reptiles. This database allows to address allometric relationships between body weight and MP content, and body weight and cytochrome P450 content. A total of 85 and 74 vertebrate species were included to assess the relationships between log10 body weight versus log10 MP, and between log10 body weight and log10 cytochrome P450 content, respectively. The resulting slopes range from 0.76 to 1.45 in a range of vertebrate species. Such data-driven allometric relationships can be used to estimate the MP content necessary for in vitro to in vivo extrapolation of in vitro clearance data. Future work includes applications of these relationships for different vertebrate taxa using quantitative in vitro to in vivo extrapolation models coupled to physiologically based kinetic models using chemicals of relevance as case studies including pesticides, contaminants and feed additives.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases, This work was supported by grants of Fondazione Telethon Italy (to N.B.‐P.), MIUR (PRIN2017 to N.B.‐P.), of the Swiss National Science Foundation (grant 320030_176088 to J.H.), of the US National Institutes of Health grants (R21NS091654 and R01NS100979 both to G.S.L.), of the Spanish Ministry of Science and Innovation (PID2019-105344RB-I00/AEI/10.13039/501100011033 toL.R.D. and E.R.), and by a Wellcome Trust Investigator Award (110061to D.M.F.v.A.)

Acute liver ischaemia-reperfusion injury (IRI), commonly encountered during liver resection and transplantation surgery, is strongly associated with unfavourable clinical outcome. However, a prompt and accurate diagnosis and the treatment of this entity remain formidable challenges. This study tested the hypothesis that 31 P-magnetic resonance spectroscopy (31 P-MRS) findings could provide reliable living images to accurately identify the degree of acute liver IRI and melatonin-pretreated mitochondria was an innovative treatment for protecting the liver from IRI in rat. Adult male SD rats were categorized into group 1 (sham-operated control), group 2 (IRI only) and group 3 (IRI + melatonin [ie mitochondrial donor rat received intraperitoneal administration of melatonin] pretreated mitochondria [10 mg/per rat by portal vein]). By the end of study period at 72 hours, 31 P-MRS showed that, as compared with group 1, the hepatic levels of ATP and NADH were significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1. The liver protein expressions of mitochondrial-electron-transport-chain complexes and mitochondrial integrity exhibited an identical pattern to 31 P-MRS finding. The protein expressions of oxidative stress, inflammatory, cellular stress signalling and mitochondrial-damaged biomarkers displayed an opposite finding of 31 P-MRS, whereas the protein expressions of antioxidants were significantly progressively increased from groups 1 to 3. Microscopic findings showed that the fibrotic area/liver injury score and inflammatory and DNA-damaged biomarkers exhibited an identical pattern of cellular stress signalling. Melatonin-pretreated mitochondria effectively protected liver against IRI and 31 P-MRS was a reliable tool for measuring the mitochondrial/ATP consumption in living animals.

This study was conducted with the objective of evaluating the combination of different ratios of soluble and insoluble linseed fibre for silver catfish (Rhamdia quelen). For this, the soluble and insoluble fractions were concentrated separately and combined in four ratios (1:0.5, 1:1, 1:2, 1:4), which were added to silver catfish diets and evaluated in a bioassay. After 45 days of receiving the experimental diets, the animals were submitted to biometry to collect data and tissues. The experimental design was completely randomized, with five treatments and four replications and the means were compared by Tukey's test (p

Liver is responsible for 90% of lipid synthesis in poultry, thus, it plays an important role in the growth of Muscovy ducks, which have a high fat deposition ability in a time-dependent manner. Therefore, male Muscovy ducks at 14, 28, 42, and 56 days were selected for body weight (BW), carcass weight (CW), subcutaneous fat thickness (SFT), abdominal fat weight (AFW), intramuscular fat content (IMF), and breast muscle fiber (BMF) diameter and density determination. Two-dimensional electrophoresis (2-DE) combining liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) was used to analyze proteomic changes in liver at each stage. The BW, CW, AFW, SFT, and BMF diameter and density were significantly increased, while IMF content was significantly decreased at 28 to 42 days of age (p &lt, 0.05). There were 57 differentially abundant protein (DEP) spots representing 40 proteins identified among the ages, in which 17, 41 and 4 spots were differentially abundant at 14 vs. 28, 28 vs. 42, and 42 vs. 56, respectively. Gene Ontology enrichment analysis found that DEPs were mostly enriched in the oxidation-reduction process, carboxylic acid metabolism, etc. Protein–protein interaction showed that catalase (CAT), triosephosphate isomerase (TPI), and protein disulfide-isomerase (PDI) were the key proteins responsible for the growth of Muscovy duck. In conclusion, 28 to 42 days of age is the crucial period for Muscovy ducks, and the ability of metabolism and antioxidants were significantly enhanced in liver.

Lipid oxidation and microbial proliferations were studied in pork loaves prepared with incorporation of blood and liver protein hydrolysates stored in aerobic and MAP packaging for 28 and 42 days at 4 ± 1 ºC. In in-vitro trials selected levels i.e. blood hydrolysate (T1 and T3-600 mg/g), and liver hydrolysate (T2 and T4-600 mg/g), control without hydrolysate (C1-00 and C2-00 mg/g) w/w of emulsion, were added into pork loaves and packaged under aerobic (C1, T1 and T2) and MAP (C2, T3 and T4) condition. Physico-chemicals as pH, water activity(,) titratable acidity, lipid-oxidations, color profile, textural indices, microbial qualities and sensorial properties were analyzed. Significant (p

To determine the effects of maternal nutrient restriction and re-alimentation on the fetal liver proteome, 48 pregnant ewes with singletons were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, a subset of ewes were fed either CON or 60% NRC requirements (RES). A subset of ewes were euthanized at day 90 of gestation (n = 7/treatment), and fetal liver samples collected. Remaining ewes were maintained on the current diet (CON-CON, n=6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n=7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver proteins were extracted, digested by trypsin and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating Tandem Mass Tags. Proteins were identified and quantified using Proteome Discoverer (v2.5, Thermo Scientific) and differential abundance analysis was performed using ANOVA and post hoc Tukey’s HSD test. Hierarchal clustering analysis showed clustering of treatments by day of gestation. However, differences were also observed between treatments. At day 90 of gestation, 23 proteins were differentially expressed in RES compared with CON among which glycyl tRNA synthetase and pyruvate carboxylase were increased 12% and 10%, respectively (P < 0.03). At day 130 of gestation, 24, 5, and 71 proteins were differentially expressed in CON-RES, RES-CON, and RES-RES, respectively, compared with CON-CON. Carnosine dipeptidase 2 was decreased 7% in CON-RES and rho associated protein kinase and glycogen synthase 2 were increased 20% and 26% in RES-CON and RES-RES, respectively, compared with CON-CON (P < 0.04). These results indicate that nutrient restriction during mid- and late-gestation impacts expression of proteins involved in gluconeogenesis, glycogenesis, and the formation of carnosine, an integral molecule in beta-oxidation, and that re-alimentation alters proteins involved in cell migration pathways. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

Toxicological effects of chemicals are mostly tested individually. However, consumers encounter exposure to complex mixtures, for example multiple pesticide residues, by consuming food such as crops, fruits or vegetables. Currently, more than 450 active substances are approved in the European Union, and there is little data on effects after combined exposure to several pesticides. Toxicological animal studies would increase enormously, if pesticide combinations had to be analyzed in vivo. Therefore, in vitro methods addressing this issue are needed. We have developed 32 immunoaffinity-based mass spectrometry assays to investigate the impact of hepatotoxic active substances on liver proteins in human HepaRG cells. Five compounds were selected based on their (dis) similar capability to modulate protein levels, and on their combined use in commercially available formulations. Four binary mixtures were prepared from these five substances and tested in different concentrations over three time points. We applied a novel statistical method to describe deviations from additivity and to detect antagonistic and synergistic effects. The results regarding the abundance of hepatotoxicity-related proteins showed additive behavior for 1323 out of 1427 endpoints tested, while 104 combinatorial effects deviating from additivity, such as antagonism or synergism were observed.

Background: The objective of this study was to investigate the effects of a novel form of biotin (magnesium biotinate) on serum glucose, lipid profile, and hepatic lipid metabolism-related genes in rats. Methods: Forty-two rats were divided into six groups and fed a standard diet-based egg white powdered diet supplemented with either d-biotin at 0.01, 1 or 100 mg/kg BW or magnesium biotinate at 0.01, 1, or 100 mg/kg BW. Results: Serum total cholesterol and triglyceride decreased with biotin by both sources (P < 0.05). Concentrations were lower with magnesium biotinate when comparing the 1 mg/kg dose groups (P < 0.05). Serum, liver, and brain biotin, and liver cyclic guanosine monophosphate (cGMP) concentrations were greater when rats were treated with magnesium biotinate versus d-biotin, particularly when comparing the 1 mg/kg and 100 mg/kg dose groups (P < 0.05). Both forms of biotin decreased the liver SREBP‐1c and FAS and increased AMPK-α1, ACC-1, ACC-2, PCC, and MCC levels (P < 0.05). The magnitudes of responses were more emphasized with magnesium biotinate. Conclusions: Magnesium biotinate, compared with a commercial d-biotin, is more effective in reducing serum lipid concentrations and in regulating gene levels of intermediary metabolism-related biomarkers.

Because the world's wild fish stocks are limited and the market demand is increasing, fish farming has become an alternative food source and a way to reduce costs for consumers. The sale of farmed as wild fish is a fraudulent practice; it is, therefore, important to find new and alternative tools that can help in the fight against fraud to protect consumers and to ensure food traceability. The proteomic profiles of farmed and wild fish differ. With this study we wanted to identify liver protein markers via two-dimensional electrophoresis that would allow us to distinguish wild from farmed gilthead seabream. The liver samples from 32 gilthead seabream, wild and farmed, were stored at -80°C before protein extraction. The samples were subjected to two-dimensional electrophoresis to detect qualitative and quantitative differences. Proteomic analysis showed a protein spot (molecular weight of ∼34 kDa and isoelectric point of ∼6.9) only in the samples from the wild gilthead seabream; liquid chromatography-tandem mass spectrometry identified the spot as ubiquitin. Ubiquitin could be a valid marker to differentiate wild from farmed gilthead seabream; it could be used to ensure continuous monitoring throughout the entire commercial chain and to fight commercial fraud. HIGHLIGHTS

In liver cirrhosis, oxidative stress plays a major role in promoting liver inflammation and fibrosis. Mitochondria dysregulation is responsible for excessive reactive oxygen species production. Therefore, in an experimental model of cirrhosis, we investigated the effect of mitochondria-targeted antioxidant mitoquinone. Liver cirrhosis was induced in Spraque-Dawley rats by common bile duct ligation (CBDL). Mitoquinone (10 mg·kg−1·day−1, oral gavage) or vehicle was administered from 3rd to 28th day after CBDL, when animals were euthanized; liver oxidative stress, inflammation, fibrosis, mitophagy were evaluated; and in vivo and ex vivo hemodynamic studies were performed. In cirrhotic rats, mitoquinone prevented liver inflammation, hepatocyte necrosis, and fibrosis at histological examination; decreased circulating TNF-α, gene expression of transforming growth factor-β1, collagen type 1a1, TNF-α, IL-6, IL-1β, tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-2, and MMP-13; and reduced hepatic oxidative stress, as shown by reduced oxidative carbonylation of the proteins, by modulating antioxidants catalase, Mn superoxide dismutase, and Cu/Zn superoxide dismutase. Furthermore, mitoquinone attenuated apoptosis by reducing hepatic protein expression of cleaved caspase-3. A selective removal of dysfunctional mitochondria was improved by mitoquinone, as shown by the increase in Parkin translocation to mitochondria. Treatment with mitoquinone normalized the weight of the spleen; however, it increased portal blood flow and reduced splenic artery intrahepatic resistance, suggesting an effect on resistance index. Mitochondria-targeted antioxidant mitoquinone improves liver inflammation and fibrosis in cirrhotic rats by reducing hepatic oxidative stress, preventing apoptosis, and promoting removal of dysfunctional mitochondria. Therefore, it may represent a promising strategy for the prevention and treatment of liver cirrhosis.

Summary Isoelectric solubilisation/precipitation (ISP) process was applied to goose liver (GL) for protein extraction. The gelation properties of proteins extracted by acid processes (ACP, pH 2.0, 2.5 and 3.0) and alkaline processes (ALP, pH 11.0, 11.5 and 12.0) were estimated, where the unextracted ground GL was set as the control. Nearly 58.39~79.00% of GL proteins were recovered by ISP treatments. High molecular weight (100~250 kDa) proteins were found to be partially hydrolysed by ACP, while few changes in proteins occurred during ALP. As evidenced by rheological and textural measurements, ALP proteins formed gels with high elasticity and superior texture, whereas ACP proteins had inferior gelation properties. Moreover, ALP proteins were able to form a highly interconnected and homogeneous three-dimensional microstructure. Predominantly, gels produced by 11.0 had optimal texture and the lowest cooking loss (P

The subcritical dimethyl ether extraction (SDEE) was applied in the preparation of liver protein powder (LPD) in this paper. As expected, the lipids and water in tuna liver were co-removed by SDEE, and LPD with a high protein content could be obtained. Besides that, the maximal protein content (88.51%) of LPD was obtained by optimized extraction conditions (liquid-solid ratio 34 mL/g, time 70 min and stirring speed 945 rpm). Furthermore, the traditional preparation technique, pH-shift, was used for comparisons. Compared with pH-shift, the higher quality LPD could by obtain by SDEE with slight fishy and excellent yield, because of SDEE could prevent the loss of nutrition constituents and remove more flavor-active components. Moreover, the functional properties of prepared LPDs were compared with soybean protein powder (SPD) and egg white powder (EWP). The results showed that the LPD prepared by SDEE possessed the greater capacities in foaming, foam stability and fat absorption. Therefore, SDEE, with the advantages of no freeze-drying procedure and relatively low pressure, would be a better alternative to prepare high-quality protein powder in the food industry.

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs – “4-way”, “7-way”, and “10-way” – each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS “physiome-on-a-chip” approaches in drug discovery.

Experiment was carried out on 111 and 13-14 weeks old mice divergently selected for low (L) and high (C) body weight over 108 generations. In leg muscle and liver cathepsin D (CatD) was determined as pepstatin sensitive activity (PSCatD), and as pepstatin-insensitive (PIA) and leupeptin-insensitive (LIA) acid autolytic activities (AAA) were measured. In leg muscle and liver all measured activities were higher in L as compared to C and control (K) mice. The percent of inhibition of LIA was lower in L then C mice in both examined tissues. In the leg muscles, in L mice protein catabolism was mostly influenced by CatD, but in the liver CatD was mostly active in K mice. CatD, PSCatD, AAA and LIA in leg muscle of L mice as compare to K were higher in female (F) by 68 %, 68.5 %, 91.3 % and 94.5 %, respectively, and in male (M) mice by 43.4 %, 54 %, 47.1 % and 64 %, respectively. The percent of inhibition by leupeptin in AAA was higher in C mice by 61.9 % in F and by 40 % in M mice. In the liver, PIA was higher by about 45 % in L and by 28.5 % in C mice as compare to K ones. There were about 36% of 30.00-39.99 μm muscle fibrils in M mice and in males of L group 40.00-49.99 μm fibrils appeared at 25% (absent in 3 weeks mice). In female, all measured fibril diameters were in higher percent in L than in C group. RNA variables were higher by about 25% (in average) in C as compare to K and L groups. Functional cell size (FCS) was lowered in L and C group as compared to K by about 10 % (in average). These results indicate on faster proteins turnover in L than in C group of mice.

Mustard oil cake is a biofertilizer widely used in agriculture and fish cultivation almost in all South East Asian Countries including India. The study was carried out to observe the effects of this biofertilizer on the liver proteins of Channa punctatus. At sublethal concentration (0.42 g/L ), fishes were exposed for a prolonged period of 35 days and amount of total liver protein (TLP) was measured. The investigation showed a low rate of liver protein synthesis in treated fish after 4 days of exposure. An increase in the amount of protein was observed between the 7th and 35th day. But such increment was below the amount of TLP of control fish, indicating physiological stress in the treated fish.

The fish may experience periods of food deprivation or starvation which produce metabolic changes. In this study, adult Rhamdia quelen males were subjected to fasting periods of 1, 7, 14, and 21 days and of refeeding 2, 4, 6, and 12 days. The results demonstrated that liver protein was depleted after 1 day of fasting, but recovered after 6 days of refeeding. After 14 days of fasting, mobilization in the lipids of the muscular tissue took place, and these reserves began to re-establish themselves after 4 days of refeeding. Plasmatic triglycerides increased after 1 day of fasting, and decreased following 2 days of refeeding. The glycerol in the plasma oscillated constantly during the different periods of fasting and refeeding. Changes in the metabolism of both protein and lipids during these periods can be considered as survival strategies used by R. quelen. The difference in the metabolic profile of the tissues, the influence of the period of fasting, and the type of reserves mobilized were all in evidence. Resumo Os peixes podem sofrer períodos de privação de alimentos ou de fome, que produzem mudanças metabólicas. Neste estudo, jundiás machos adultos foram submetidos a jejum períodos de 1, 7, 14 e 21 dias e realimentação 2, 4, 6, e 12 dias. Os resultados demonstraram que a proteína do fígado foi esgotada depois de um dia de jejum, mas restabeleceu após 6 dias de realimentação. Após 14 dias de jejum, ocorreu a mobilização dos lípidos no tecido muscular sendo que estas reservas começaram a re-estabelecer-se após 4 dias de realimentação. Os triglicérides plasmáticos aumentam após um dia de jejum, e diminuiram após 2 dias de realimentação. O glicerol no plasma oscilou constantemente durante os diferentes períodos de jejum e realimentação. As alterações no metabolismo de proteína e lipídios durante estes períodos podem ser consideradas uma estratégias de sobrevivência utilizada pelo Rhamdia quelen. Sendo que a diferença no perfil metabólico tecidual bem como a influência do período de jejum e o tipo de reserva a ser mobilizada foram observadas neste estudo.

The postprandial state is characterized by a storage of nutrients in the liver, muscle, and adipose tissue for later utilization. In the case of a protein-rich meal, amino acids (AA) stimulate glucagon secretion by the α-cell. The aim of the present study was to determine the impact of the rise in glucagon on AA metabolism, particularly in the liver. We used a conscious catheterized dog model to recreate a postprandial condition using a pancreatic clamp. Portal infusions of glucose, AA, and insulin were used to achieve postprandial levels, while portal glucagon infusion was either maintained at the basal level or increased by three-fold. The high glucagon infusion reduced the increase in arterial AA concentrations compared with the basal glucagon level (−23%, P < 0.05). In the presence of high glucagon, liver AA metabolism shifted toward a more catabolic state with less protein synthesis (−36%) and increased urea production (+52%). Net hepatic glucose uptake was reduced modestly (−35%), and AA were preferentially used in gluconeogenesis, leading to lower glycogen synthesis (−54%). The phosphorylation of AMPK was increased by the high glucagon infusion (+40%), and this could be responsible for increasing the expression of genes related to pathways producing energy and lowering those involved in energy consumption. In conclusion, the rise in glucagon associated with a protein-rich meal promotes a catabolic utilization of AA in the liver, thereby, opposing the storage of AA in proteins.

Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice. This was associated with a significant downregulation of the hepatic LXR targets, including Abcg5/g8. Pharmacologic induction of LXR promoted the delivery of total tracer output into feces in db/db mice, partly due to increased liver and small intestine Abcg5/Abcg8 gene expression. Notably, a favorable upregulation of the hepatic levels of ABCG5/G8 and NR1H3 was also observed postoperatively in morbidly obese patients, suggesting a similar LXR impairment in these patients. In conclusion, our data show that downregulation of the LXR axis impairs cholesterol transfer from macrophages to feces in db/db mice, whereas the induction of the LXR axis partly restores impaired m-RCT by elevating the liver and small intestine expressions of Abcg5/g8. © 2017 Elsevier Inc.

This study assessed seasonal variation of total liver proteins level (LPLs) and biotransformation biomarkers in two fish species, G. niger and Z. ophiocephalus, during a one year-survey in the low contaminated Ghar-El-Melh lagoon, Tunisia. Analyzed biomarkers were compared with physiological indexes such as the condition index, hepato-somatic index, and gonado-somatic index and environmental parameters. A significant annual rhythms of glutathione-S-transferase and ethoxyresorufin-O-deethylase activities were validated by cosinor. The highest peak (acrophase) of activities occurred in summer likely related to the elevated seawater temperature. Midline Estimating Statistic of Rhythm and amplitudes were higher in Z. ophiocephalus than in G. niger. The results showed, as well, an acrophase of (LPLs) in spring coinciding with reproductive period in Z. ophiocephalus and beginning of reproductive period in G. niger. This study established a baseline for the selected enzymatic activities in gobies, which required information for a correct interpretation of biomarker responses in environmental monitoring.

Effect of AGREIN on the mitotic behavior was studied in Vicia faba. AGREIN was tested by the following concentrations "1.5, 2.5 and 3.5 " g/L which showed high rats of aberrations in most phases of mitotic division and the highest incidence of aberration was 26% after treating with the highest concentration comparing with the control. As for the effect of AGREIN on the meiotic behaviors of Vicia faba, the rate of aberration increased with increasing the concentration on both the first and the second meiosis and the highest percentage obtained was 46% with the highest concentration comparing with the control. AGERIN induced considerable alterations in the electrophoritic profiles of the seed proteins of Vicia faba. The maximum number of bands was 17. Comparison between the treated samples and the control revealed the existence of some variations in the protein banding pattern between the treated samples on the mice treated with doses of "1.5, 2.5 and 3.5" g/L of AGREIN. The electrophoresis patterns of mice liver protein indicated that the maximum number of bands was 24 and some protein bands existed in control and disappeared in the treated groups and vice versa. Tumer suppressor gene p53 was affected by treating the mice with the three doses of AGERIN which revealed the occurrence of mutation. Such mutation could reflect a serious hazard to those handling this bio-insecticide.

Cytotoxic agents has been widely used for the treatment various human malignancies. Cisplatin and etoposide are chemotheraupeutic agents which are used for treatment of metastatic cancers, solid tumors and neoplasm. The drug is known to exert its toxic effect on hepatic and renal tissue by altering its antioxidant response of these organs. In the present study both the drugs Cisplatin and etoposide were analyzed for its effects on hepatic protein status. Cisplatin has shown to cause consequential alterations in protein levels as compared to etoposide treated hepatic tissue. The protein with molecular weight 44.46, 13.8, 51.2 kd was downregulated and other ranging from 16.98-38.9 kd did not show any expression as compared to controls. In addition etoposide studies revealed overexpression in protein level ranging from molecular weight 14.45-33.11 kd which might suggest significant role in organ protection. Some of protein bands ranging from 25.12 to 51.29 kd showed similar pattern of expression compared to controls. Present studies might provide us clues of important role of these protein in combating free radical induced oxidative stress on the tissue.

© 2016, Springer Science+Business Media New York. The functional (emulsifying, gelling and foaming) properties of liver protein fractions as well as their molecular weight distribution and surface hydrophobicity were investigated and compared to commercial proteins. Two protein fractions were characterized: water soluble (WSLP) and WSLP combined with salt soluble liver proteins (W + SSLP). The effect of salt concentrations was also investigated (0, 1.8 and 3.4 % NaCl). Both WSLP and W + SSLP displayed good emulsifying properties and foam stability. However, their gelling properties were rather poor. An increase in salt concentration decreased the emulsifying properties of WSLP while the effect on W + SSLP was less pronounced. Addition of 1.8 % NaCl increased foaming ability of WSLP and W + SSLP while foam stability was not affected. Further increase of NaCl (3.4 %) decreased both foaming ability and foam stability and is probably attributed to refolding of the protein molecules because of the higher level of hydrophobic groups with 3.4 % NaCl. Gel forming ability of WSLP and W + SSLP containing 0 % was higher compared to high salt concentrations. However, higher salt concentrations shifted onset gelation temperature of WSLP and W + SSLP to lower temperatures probably due to partial unfolding of the proteins as indicated by an increase of the surface hydrophobicity. ispartof: Food and Bioprocess Technology vol:9 issue:6 pages:970-980 status: published

Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data compared with a previous study in females, “Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats” (Miller et al., 2016) [1]. Specifically, proteomic investigation of liver protein patterns obtained by 2D-DIGE was performed and differences between animals groups recorded, based on the factors exposure, thyroid status and gender. All proteins with significantly changed abundance in any of these comparisons were identified by mass spectrometry. General, hormone and proteomic data of both the present and the previous studies are discussed in Miller et al. (2016) [1] and in ''Gender specific differences in the liver proteome of rats exposed to hexabromocyclododecane (HBCD)'' Miller et al. (2016) [2]. Keywords: HBCD, Proteomics, Rat, Liver, Hypothyroidism, Gender-specific effects