Search results for: liver fibrogenesis

Authors: Seyyed Javad Ziaolhagh

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Background: The purpose of present study was to investigate, the effects of anabolic steroid Boldenone (BOL) with eight weeks of resistance training on structural changes in rat liver. Method: 21 Male adult Wistar rats, 12 weeks old and 228/53±7/94 g initial body weight were randomly assigned to three groups: group1: Control+ Placebo (C), group2: training+ Placebo (T), group3: Boldenone intramuscular injections 5mg/kg (B). The endurance training protocol consisted three exercise sessions weekly started by a 30-minute run with the speed of 12 m/min and lasted by 60min run with the speed of 30 m/min in 8 weeks. At the end of the experiment, for light microscopic study Slides were prepared. Results: Sections stained of rat's livers showed no any cell degeneration and cytoplasmic lipid vacuoles in all groups, but few samples were seen. Indeed, congested blood sinusoids, cell infiltration and degeneration were seen in the Boldenone-treated group. Hepatotoxic effects were severe in group treatment received 5 mg/kg and directly depended on the doses. Indeed, training group was no any hepatocyte degeneration, inflammation and congestion. Conclusion: The present results showed that BOL has a marked adverse effect on the liver tissue, even with low– dose and endurance training. As a result, athletes should aware of Boldenone dosage consumption.

Keywords: anabolic androgenic steroids, Boldenone, blood congestion, cellular inflammation, cellular degeneration, lipid vocuolations, endurance training

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Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

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Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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Authors: Hager Elsheikh, Juliane Glaubitz, Frank Ulrich Weiss, Matthias Sendler

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Aim: Acute pancreatitis (AP) and chronic pancreatitis (CP) are both accompanied by a prominent immune response which influences the course of disease. Whereas during AP the pro-inflammatory immune response dominates, during CP a fibroinflammatory response regulates organ remodeling. The transcription factor signal transducer and activator of transcription 6 (STAT6) is a crucial part of the Type 2 immune response. Here we investigate the role of STAT6 in a mouse model of AP and CP. Material and Methods: AP was induced by hourly repetitive i.p. injections of caerulein (50µg/kg/bodyweight) in C57Bl/6 J and STAT6-/- mice. CP was induced by repetitive caerulein injections 6 times a day, 3 days a week over 4 weeks. Disease severity was evaluated by serum amylase/lipase measurement, H&E staining of pancreas. Pancreatic infiltrate was characterized by immunofluorescent labeling of CD68, CD206, CCR2, CD4 and CD8. Pancreas fibrosis was evaluated by Azan blue staining. qRT-PCR was performed of Arg1, Nos2, Il6, Il1b, Col3a, Socs3 and Ym1. Affymetrix chip array analyses were done to illustrate the IL4/IL13/STAT6 signaling in bone marrow derived macrophages. Results: AP severity is mitigated in STAT6-/- mice, as shown by decreased serum amylase and lipase, as well as histological damage. CP mice surprisingly showed only slightly reduced fibrosis of the pancreas. Also staining of CD206 a classical marker of alternatively activated macrophages showed no decrease of M2-like polarization in the absence of STAT6. In contrast, transcription profile analysis in BMDM showed complete blockade of the IL4/IL13 pathway in STAT6-/- animals. Conclusion: STAT6 signaling pathway is protective during AP and mitigates the pancreatic damage. During chronic pancreatitis the IL4/IL13 – STAT6 axisis involved in organ fibrogenesis. Notably, fibrosis is not dependent on a single signaling pathway, and alternative macrophage activation is also complex and involves different subclasses (M2a, M2b, M2c and M2d) which could be independent of the IL4/IL13 STAT6 axis.

Keywords: chronic pancreatitis, macrophages, IL4/IL13, Type immune response

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Authors: Luana N. Cardozo, Debora A. S. Coutinho, Fabiola Lagher, Bruno J. G. Silva, Ivonilce Venture, Mainara Tesser, Graciela Venera

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Ostrich oil is used as food in Brazil, and it has been the subject of scientific research because it contains essential fatty acids (Omega 3, 6, 7, and 9), which provide benefits to human health. Alkylglycerols are lipid ethers consisted of a saturated or unsaturated hydrocarbon chain joined by ether-type bonding to one of the glycerol hydroxyls. It is known that supplementation with alkylglycerols can act significantly on the functioning of immune system cells, both in pathological situations and in homeostasis. Objective: Analyze the presence of alkylglycerols in ostrich oil. Methods: The ostrich oil was bought from an industry that manufactures the product for sale as food, located in Mirante da Serra, northern Brazil. The samples were sent for analysis to the chemistry department of the Federal University of Paraná, where they were analyzed by the gas chromatography method. Results: The analysis of the ostrich oil presented alkylglycerols in area 514505154. Comparison, it is possible to observe that shark liver oil contains the area 26190196, and the difference between both is highly significant. Conclusion: The importance of alkylglycerol supplementation for the immune system is known. The analysis of the results made it possible to verify the presence of alkylglycerols in the ostrich oil, which is five times higher than in the shark liver oil, that would be the largest source food, but was surpassed by the ostrich oil until the present time. The present study emphasizes that ostrich oil can be considered a food source of alkylglycerols and may play a promising role in the immune system because it contains such substance, but further studies are needed to prove its performance in the body.

Keywords: ostrich oil, nutritional composition, alkylglycerols, food

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Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

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Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

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Authors: Jelena Nedeljković Trailović, Marko Vasiljević, Jog Raj, Hunor Farkaš, Branko Petrujkić, Stamen Radulović, Gorana Popvić

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The experiment was performed on a total of 99 one-day-old broilers of Cob 500 provenance, which were divided into IX equal groups. Broilers of the E-I group were fed 0.25 mg T-2 toxin/kg feed, E-II and E-III groups 0.25 mg T-2 toxin/kg feed with the addition of 1 kg/t and 3 kg/t of the mycotoxin detoxification agent MDA, respectively. The E-IV group received 1 mg of T-2 toxin/kg of feed, and the broilers of E-V and E-VI groups received 1 mg of T-2 toxin/kg of feed with the addition of 1 kg/t and 3 kg/t of the MDA detoxification preparation, respectively. The E-VII group received commercial feed without toxins and additives, the E-VIII and E-IX groups received feed with 1kg/t and 3kg/t of the MDA detoxification preparation. The trial lasted 42 days. Observing the results obtained on the 42nd day of the experiment, we can conclude that the change in the absolute mass of the spleen occurred in the broilers of the E-IV group (1.66±0.14)g, which was statistically significantly lower compared to the broilers of the E-V and E-VI groups (2.58±0.15 and 2.68±0.23)g. Heart mass was significantly statistically lower in broilers of group E-IV (9.1±0.38)g compared to broilers of group E-V and E-VI (12.23±0.5 and 11.43±0.51)g. It can be concluded that the broilers that received 1 kg/t and 3 kg/t of the detoxification preparation had an absolute mass of organs within physiological limits. Broilers of the E-IV group achieved the lowest BM during the experiment (on the 42nd day of the experiment 1879±52.73)g, they were significantly statistically lower than the BW of broilers of all experimental groups. This trend is observed from the beginning to the end of the experiment. The protective effect of the detoxification preparation can be seen in broilers of the E-V group, that had a significantly statistically higher BM on the 42nd day of the experiment (2225±58.81)g compared to broilers of group E-IV. Broilers of E-VIII group (2452±46.71) g, which received commercial feed with the addition of 1 kg/t MDA preparation, had the highest BMI at the end of the experiment. At the end of the trial on the 42nd day, blood samples were collected from broilers of the experimental groups that received T-2 toxin and MR detoxification preparations in different concentrations. Also, liver and breast musculature samples were collected for testing for the presence and content of T-2 toxin, HT-2 toxin, T-2 tetraol and T-2 triol. Due to very rapid elimination from the blood, no remains of T-2 toxin and its metabolites were detected in the blood of broilers of groups E-I to E-VI. In the breast muscles, T-2 toxin residues below LoQ < 0.2 (μg/kg) were detected in all groups that received T-2 toxin in food, the highest value was recorded in the E-IV group (0.122 μg/kg and the lowest in E -VI group 0.096 μg/kg). No T-2 toxin residues were detected in the liver. Remains of HT-2 were detected in the breast muscles and livers of broilers from E-IV, E-V and E-VI groups, LoQ < 1 (μg/kg); for the breast muscles: 0.054, 0.044 and 0.041 μg/kg, and for the liver: 0.473, 0.231 and 0.185 μg/kg. Summing up all the results, a partial protective effect of the detoxification preparation, added to food in the amount of 1kg/t, can be seen.

Keywords: T-2 toxin, bloiler, MDA, mycotoxuns

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Authors: Nahida Sultana

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Globally, an estimated 58 million people have chronic hepatitis C virus infection, with about 1.5 million new infections occurring per year. The hepatitis C virus is a blood-borne virus, and most infections occur through exposure to blood from unsafe injection practices, unsafe health care, unscreened blood transfusion, injection drug use, and sexual practices that lead to exposure to blood. Hepatitis C virus (HCV) causes chronic infections that mainly affect the liver leading to liver diseases. This study aimed to determine whether there is any significant association between HCV transmission risk factors in relation to genotypes in HCV-infected Bangladeshi patients. After quantification of HCV viral load, 36 samples were randomly selected for HCV genotyping and risk factor measurement. A greater proportion of genotype 1 (p > 0.05) patients (40%) underwent blood transfusion compared to patients (22.6%) with genotype 3 infections. More genotype 1 patient underwent surgery and invasive procedures (20%), and rather than those with genotype 3 patients (16.1%). The history of IDUs (25.8%) and sexual exposure (3.2%) are only prevalent in genotype 3 patients and absent in patients with genotype 1 (p >0.05). There was no significant statistical difference found in HCV transmission risk factors (blood transfusion, IDUs, Surgery& interventions, sexual transmission) between patients infected with genotypes 1 and 3. In HCV infection, genotype may have no relation to transmission risk factors among Bangladeshi patients.

Keywords: HCV genotype, alanine aminotransferase (ALT), HCV viral load, IDUs

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Authors: Hanan A. Soliman, Mohamed A. El-Desouky, Walaa G. Hozayen, Rasha R. Ahmed, Amal K . Khaliefa

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Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

Keywords: antioxidants, dexamethasone, hyperglycemia, hyperlipidemia

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Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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Doxorubicin (DOX), an anthracycline antibiotic is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w. day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein, and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In conclusion, it can be supposed that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

Keywords: doxorubicin, purslane, hepatotoxicity, antioxidants

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Authors: Eqbal M. A. Dauqan, A. Aminah

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The aim of the present study was to evaluate the blood lipid profile and liver lipid peroxidation in normal rat fed with different concentrations of Acacia senegal and Acacia seyal. Thirty six Sprague Dawley male rats each weighing between 180-200g were randomly divided into two groups. Each group contains eighteen rats and were divided into three groups of 6 rats per group. The rats were fed ad libitum with commercial rat’s feed and tap water containing different concentrations of Acacia senegal and Acacia seyal (3% and 6%) for 4 weeks. The results at 4 weeks showed that there was no significant difference (p≤0.05) in the total cholesterol (TC) and triglycerides (TG) between the control group and treated groups while the results for the high density lipoprotein (HDL-C) showed a significant decrease (P≥0.05) at the 3% and 6% of gum arabic treated groups compared to control group. There was a significant increase (P≥0.05) in low density lipoprotein (LDL-C) with 3% and 6% of gum Arabic (GA) groups compared to the control group. The study indicated that there was no significant (p≤0.05) effect on TC and TG but there was significant effect (P≥0.05) on HDL-C and LDL-C in blood lipid profile of normal rat. The results showed that after 4 weeks of treatment the malondialdehyde (MDA) value in rat fed with 6% of A. seyal group was significantly higher (P≥0.05) than control or other treated groups of A. seyal and A. senegal studied. Thus, the two species of gum arabic did not have beneficial effect on blood lipid profile and lipid peroxidation.

Keywords: Acacia senegal, acacia seyal, lipid profile, lipid peroxidation, malondialdehyde (MDA)

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Authors: Ertuğrul Yılmaz

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One of the most important occupational groups in the food chain from farm to fork is a veterinary medicine. This occupational group, which has important duties in the prevention of many zoonotic diseases and in public health, takes place in many critical control points from soil to our kitchen. It has important duties from mycotoxins transmitted from the soil to slaughterhouses or milk processing facilities. Starting from the soil, which constitutes 70% of mycotoxin contamination, up to the TMR made from raw materials obtained from the soil, there are all critical control points from feeding to slaughterhouses and milk production enterprises. We can take the precaution of mycotoxins such as Aflatoxin B1, Ochratoxin, Zearalenone, and Fumonisin, which we encounter on farms while in the field. It has been reported that aflatoxin B1 is a casenerogen and passes into milk in studies. It is likely that many mycotoxins pose significant threats to public health and will turn out to be even more dangerous over time. Even raw material storage and TMR preparation are very important for public health. The danger of fumonisin accumulating in the liver will be understood over time. Zoonotic diseases are also explained with examples. In this study, how important veterinarians are in terms of public health is explained with examples. In the two-year mycotoxin screenings, fumonisin mycotoxin was found to be very high in corn and corn by-products, and it was determined that it accumulated in the liver for a long time and remained cornic in animals. It has been determined that mycotoxins are present in all livestock feeds, poultry feeds, and raw materials, not alone, but in double-triple form. Starting from the end, mycotoxin scans should be carried out from feed to raw materials and from raw materials to soil. In this way, we prevent the transmission of mycotoxins to animals and from animals to humans. Liver protectors such as toxin binders, beta-glucan, mannan oligosaccharides, activated carbon, prebiotics, and silymarin were used in certain proportions in the total mixed ratio, and positive results were obtained. Humidity and temperature controls of raw material silos were made at certain intervals. Necropsy was performed on animals that died as a result of mycotoxicosis, and macroscopic photographs were taken of the organs. We have determined that the mycotoxin screening in experimental animals and the feeds made without detecting the presence and amount of bacterial factors affect the results of the project to be made. For this, a series of precautionary plans have been created, starting from the production processes.

Keywords: mycotoxins, feed safety, processes, public health

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Authors: J. C. Akan, F. I. Abdulrahman, Z. M. Chellube

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The aim of this study was to determine the levels of some organochlorine (o, p-DDE, p,p’-DDD, o,p’-DDD, p,p’-DDT, p,p’-DDT, α-BHC, γ-BHC, lindane, Endosulfan sulphate, dieldrin and aldrin and organophosphorus (Dichlorvos, Diazinon, Chlorpyrifos, fenitrothion and Fenitrothion) pesticide residues in the gills, liver, stomach, kidney and flesh of four fish species (Tilapia zilli, Clarias anguillaris Hetrotis niloticus and Oreochronmis niloticus) between the periods of September 2010 to October, 2011. Samples were collected from Kwantan turare in Lake Chad, Baga, Borno State, Nigeria. Extraction of the fish samples and de-fattening of the fish sample extracts were performed using standard procedures. Analysis of the fish samples for pesticide residues were carried out using Shimadzu GC/MS (GC – 17A), equipped with fluorescence detector. Large differences in the levels of pesticide residues were observed between tissues within each fish. The concentrations of all the organophosphorus pesticides were higher in the organs of Oreochronmis niloticus, while Hetrotis niloticus shows the lowest. For organochlorine pesticides, the organs of Tilapia zilli showed the highest concentrations, while Hetrotis niloticus shows the lowest. The highest pesticide concentrations were observed in gills and liver tissues of all the species of fish study, while the lowest concentrations were observed in flesh. Based on the above results, it can therefore be concluded that the concentrations of pesticide in the four fish species study did exceed the permissible limits set by FAO and FEPA.

Keywords: organochlorine, organophosphorus, pesticides, accumulation, fish, lake chad

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: Ayda Youssef, Mohammed Ali Khalaf, Tarek Rafaat

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Background: Langerhans cell histiocytosis (LCH) is a rare multi-systemic disease that shows an abnormal proliferation of these kinds of cells associated with a granular infiltration that affects different structures of the human body, including the lung, liver, spleen, lymph nodes, brain, mucocutaneous, soft tissue (head and neck), and salivary glands. Evaluation of the extent of disease is one of the major predictors of patient outcome. Objectives: To recognize the pathogenesis of Langerhans cell histiocytosis (LCH), describe the radiologic criteria that are suggestive of LCH in different organs rather than the bones and to illustrate the appropriate differential diagnoses for LCH in each of the common extra-osseous sites. Material and methods: A retrospective study was done on 150 biopsy-proven LCH patients from 2007 to 2012. All patients underwent imaging studies, mostly US, CT, and MRI. These patients were reviewed to assess the extra-skeletal manifestations of LCH. Results: In 150 patients with biopsy-proven LCH, There were 33 patients with liver affection, 5 patients with splenic lesions, 55 patients with enlarged lymph nodes, 9 patient with CNS disease and 11 patients with lung involvement. Conclusions: Because of the frequent LCH children and evaluation of the extent of disease is one of the major predictors of patient outcome. Radiologist need to be familiar with its presentation in different organs and regions of body outside the commonest site of affection (bones). A high-index suspicion should be raised a biopsy is recommended in the presence of radiological suspicion. Chemotherapy is the preferred therapeutic modality.

Keywords: langerhans cell histiocytosis, extra-skeletal, pediatrics, radiology

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Authors: Adedoyin Akintunde Adedayo, Onilude Abiodun Anthony

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The continuous usage of synthetic antibiotics in livestock production has led to the resistance of microbial pathogens. This has prompted research to find alternative sources. This study aims to compare the growth and intestinal health of broilers fed scent leaf meal (SLM) as an alternative to synthetic antibiotics. The study used a completely randomized design (CRD) with 300 one-week-old Arbor Acres broiler chicks. The chicks were divided into six treatments with five replicates of ten birds each. The feeding trial lasted 49 days, including a one-week acclimatization period. Commercial broiler diets were used. The diets included a negative control (no leaf meal or antibiotics), a positive control (0.10% oxy-tetracycline), and four diets with different levels of SLM (0.5%, 1.0%, 1.5%, and 2.0%). The supplementation of both oxy-tetracycline and SLM improved feed intake during the finisher phase. Birds fed SLM at a 1% inclusion level showed significantly (P<0.05) improved average body weight gain (ABWG), lowered feed-to-gain ratio, and cost per kilogram of weight gain compared to other diets. The mortality (2.0%) rate was significantly higher in the negative control group. White blood cell levels varied significantly (P<0.05) in birds fed SLM-supplemented diets, and the use of 2% SLM led to an increase in liver weight. However, welfare indices were not compromised.

Keywords: Arbor Acres, phyto-biotic, synthetic antibiotic, white blood cell, liver weight

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Authors: Gintarė Sauliutė, Gintaras Svecevičius

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Landfill leachates contain a number of persistent pollutants, including heavy metals. They have the ability to spread in ecosystems and accumulate in fish which most of them are classified as top-consumers of trophic chains. Fish are freely swimming organisms; but perhaps, due to their species-specific ecological and behavioral properties, they often prefer the most suitable biotopes and therefore, did not avoid harmful substances or environments. That is why it is necessary to evaluate the persistent pollutant dispersion in hydroecosystem using fish tissue metal concentration. In hydroecosystems of hybrid type (e.g. river-pond-river) the distance from the pollution source could be a perfect indicator of such a kind of metal distribution. The studies were carried out in the Kairiai landfill neighboring hybrid-type ecosystem which is located 5 km east of the Šiauliai City. Fish tissue (gills, liver, and muscle) metal concentration measurements were performed on two types of ecologically-different fishes according to their feeding characteristics: benthophagous (Gibel carp, roach) and predatory (Northern pike, perch). A number of mathematical models (linear, non-linear, using log and other transformations) have been applied in order to identify the most satisfactorily description of the interdependence between fish tissue metal concentration and the distance from the pollution source. However, the only one log-multiple regression model revealed the pattern that the distance from the pollution source is closely and positively correlated with metal concentration in all predatory fish tissues studied (gills, liver, and muscle).

Keywords: bioaccumulation in fish, heavy metals, hydroecosystem, landfill leachate, mathematical model

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Authors: Ahlem Bahi, Youcef Necib, Sakina Zerizer, Cherif Abdennour, Mohamed Salah Boulakoud

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Mercury (II) is a highly toxic metal which induces oxidative stress in the body. In this study, we aimed to investigate the possible protective effect of olive oil, an antioxidant agent, against experimental mercury toxicity in rat model. Administration of mercuric chloride induced significant increase in serum: ALT, AST, and LPA activities; interleukine1, interleukine6, tumor necrosis factor α (TNFα), creatinine, urea, and uric acid levels. Mercuric chloride also induced oxidative stress, as indicate by decreased tissue of GSH level, GSH-Px, and GST activities along with increase the level of lipid peroxidation. Furthermore, treatment with mercuric chloride caused a marked elevation of kidney and liver weight and decreased body weight. Virgin olive oil treatment markedly reduced elevated serum: AST, ALT, and LPA activities; interleukine1, interleukine6, tumor necrosis factor α (TNFα), creatinine, urea, and uric acid levels and contracted the deterious effects of mercuric chloride on oxidative stress markers changes caused by HgCl2 in tissue as compared to control group. Our results implicate that mercury induced oxidative damage in liver and kidney tissue protected by virgin olive oil, with its antioxidant effects.

Keywords: mercury, antioxidant enzymes, pro-inflammatory cytokine, virgin olive oil, lipid peroxidation

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Authors: Wassim Guermazi, Saoussan Boukhris, Neila Annabi Trabelsi, Tarek Rebai, Alya Sellami-Kamoun, Habib Ayadi

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This work investigates the protective effects of the microalga Halamphora sp. extract (H. Ext) as a natural product on lead-intoxicated liver and kidney human cells in vitro and in vivo on rats wistar. HepG2 cells line derived from human hepatocellular carcinoma and HEK293 cells line derived from human embryonic kidney were used for the in vitro study. The analysis of the fatty acids methyl esters of the extract was performed by a GC/MS. Four groups of rats, each of which was composed of six animals, were used for the in vivo experiment. The pretreatment of HepG2 and HEK293 cells line with the extract (100 µg mL-1) significantly (p < 0.05) protected against cytotoxicity induced by lead exposure. In vivo, the biochemical parameters in serum, namely malondialdehyde level (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, were measured in supernatants of organ homogenates. H. Ext was found to be rich in fatty acids, essentially palmitic and palmitoleic accounting respectively 29.46% and 42.07% of total fatty acids. Both in vitro and in vivo, the co-treatment with H. Ext allowed the protection of the liver and kidney cells structure, as well as the significant preservation of normal antioxidant and biochemical parameters in rats. Halamphora extract rich in fatty acids has been proven to be effective in protection against Pb-induced toxicity.

Keywords: microalga extract, human cells line, fatty acid, lead exposure, oxidative stress, rats

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Authors: So Young Kim, Eun-Young Kwon, Bora Choi, Mi Kyeong Yu, Seon Jeong Lee, Myung-Sook Choi

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Lemon (Citrus limon) has various beneficial effect. Eriocitrin (eriodictyol 7-rutinoside) is the main ingredient of lemon fruit and is known to have antioxidative effects. However, there has been little research about the effects of eriocitrin on obesity and regulation of lipid profiles levels. In the present study, we investigated the anti-obesity and lipid-lowering effects of eriocitrin in mice fed high-fat diet (HFD). The 4 week-old male C57BL/6 mice were randomly divided into two groups and were fed HFD (20% fat, w/w) and HFD supplemented with eriocitrin (0.005%, w/w, EC) for 16 weeks. Food intake, body weight and white adipose tissue weight (WAT) were measured and plasma free fatty acid (FFA), apolipoprotein (Apo) B100 level and hepatic enzyme activity were analyzed. No differences were shown between the HFD and EC groups in body weight and food intake. However EC supplementation significantly reduced the weights of epididymal, subcutaneous and total WAT. In addition, the levels of plasma FFA and Apo B100 were significantly decreased in the EC group compared with the HFD group. Moreover, the activities of glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) related to fatty acids synthesis were significantly lower in the EC group than in the HFD group in liver. Therefore, this study indicates that eriocitrin has beneficial effects on adiposity and nonalcholic fatty liver diseases by modulating hepatic lipid-regulating enzyme activities and plasma lipid profile.

Keywords: antiobesity, eriocitrin, high fat diet, lipid lowering

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Authors: Hala Demerdash, Ola M. Zanaty, Emad Eldin Arida

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Background: This study investigated the micoRNA expression changes induced by Sevoflurane and Propofol and their effects on liver functions. Patients and methods: The study was designed as randomized controlled study, carried out on 200 adult patients, scheduled for major surgeries under general anesthesia (GA). Patients were randomly divided into four groups; groups SC and PC included chronic hepatitis C (CHC) patients where SC group are patients receiving Sevoflurane, and PC group are patients receiving Propofol anesthesia. While S and P groups included non- hepatitis patients; S group are patients receiving Sevoflurane and P group are patients receiving Propofol. Anesthesia in Group S and SC patients was maintained by sevoflurane, while anesthesia in Group P and PC patients was maintained by propofol infusion. Blood samples were analyzed for PT, PTT and liver enzymes. Serum samples were analyzed for microRNA before and after surgery. Results: Results show miRNA-122 and miRNA-21 were absent in serum of S and P groups in pre-operative samples. However, they were expressed in SC and PC groups. In post-operative samples; miRNA-122 revealed an increased expression in all groups; with more exaggerated response in SC group. On the other hand miRNA-21 revealed increased expression in both SC and PC groups; a slight expression in S group with absent expression in P group. There was a post-operative negative correlation between miR-122 and ALT (r=-0.46) in SC group and (r=-0.411) in PC group and positive correlation between ALT and miR-21 (r=0.335) in SC group and (r=0.379) in PC group. The amount of blood loss was positively correlated with miR-122 (r=0.366) in SC group and (r=0.384) in PC group. Conclusion: Propofol anesthesia is safer than Sevoflurane anesthesia in patients with CHC. Sevoflurane and Propofol anesthesia affect miRNA expression in both CHC and non-hepatitis patients.

Keywords: anesthesia, chronic hepatitis C, micoRNA, propofol, sevoflurane

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Authors: Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Amornnat Thuppia, Nuntiya Somparn

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Several dietary and herbal plants have been shown to possess cytoprotective and antioxidant effects with various mechanisms of action. The aim of this study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Ocimum americanum (OA), commonly known as American basil or 'hoary basil', in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 100, 200 and 400 mg/kg for 28 days. Phytochemical screening of plant extracts revealed the presence of alkaloid, cardiac glycosides, tannin and steroid compounds. The extract contained phenolic compounds 36.91 ± 0.66 mg of gallic acid equivalents per gram OA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 41.27 ± 1.86 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. The protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased compared with normal control. Consistent with the induction of γ-GCL protein expression significantly reduction of serum oxidative stress marker malondialdehyde (MDA) was found in rat treated with OA extract compared with control. Taken together, this study provides evidence that Ocimum americanum exhibits direct antioxidant properties and can induce cytoprotective enzyme in vivo.

Keywords: antioxidant, γ-glutamylcysteine ligase, MDA, Ocimum americanum

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Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

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Authors: Ahmet Uyar, Zabit Yener, Abdulahad Dogan

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(1). The ameliorative potential and antioxidant capacity of an extract of Urtica dioica seeds (UDS) were investigated using histopathological changes in liver and kidney of broiler, measuring serum marker enzymes, antioxidant defence systems and lipid peroxidation (malondialdehyde (MDA)) content in various tissues of broilers exposed to aflatoxin (AF). (2). A total of 32 broilers were divided randomly into 4 groups: control, UDS extract-treated, AF-treated and AF+UDS extract-treated. Broilers in control and UDS extract-treated groups were fed on a diet without AF. The AF-treated group and AF+UDS extract-treated groups were treated with an estimated 1 mg total AF/kg feed. The AF+UDS extract groups received in addition 30 ml UDS extract/kg diet for 21 days. (3). The AF-treated group had significantly decreased body weight gain when compared to the other groups. (4). Biochemical analysis showed a small increase in the concentrations of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and lactate dehydrogenase in the AF-treated group compared to that of the control group, whereas concentrations of these enzymes were decreased in the AF+UDS group compared to that of the AF-treated group. (5). Administration of supplementary UDS extract helped restore the AF-induced increase in MDA and reduced the antioxidant system towards normality, particularly in the liver, brain, kidney and heart. Hepatorenal protection by UDS extracts was further supported by the almost normal histology in AF +UDS extract-treated group as compared to the degenerative changes in the AF-treated broilers. (6). It was concluded that UDS extract has a protective hepatorenal effect in broilers affected by aflatoxicosis, probably acting by promoting the antioxidative defence systems.

Keywords: aflatoxicosis, biochemistry, broiler, histopathology, Urtica dioica seed extract

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Jin Choi, Zahra Aminikhoei, Yi-Oh Kim, Sang-Min Lee

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A 4 × 2 factorial experiment was conducted to determine the optimum dietary protein and lipid levels for juvenile fancy carp, Cyprinus carpio var. koi. Eight experimental diets were formulated to contain four protein levels (200, 300, 400, and 500 g kg-1) with two lipid levels (70 and 140 g kg-1). Triplicate groups of fish (initial weight, 12.1±0.2 g fish-1) were hand-fed the diets to apparent satiation for 8 weeks. Weight gain, daily feed intake, feed efficiency ratio and protein efficiency ratio were significantly (P < 0.0001) affected by dietary protein level, but not by dietary lipid level (P > 0.05). Weight gain and feed efficiency ratio tended to increase as dietary protein level increased up to 400 and 500 g kg-1, respectively. Daily feed intake of fish decreased with increasing dietary protein level and that of fish fed diet contained 500 g kg-1 protein was significantly lower than other fish groups. The protein efficiency ratio of fish fed 400 and 500 g kg-1 protein was lower than that of fish fed 200 and 300 g kg-1 protein. Moisture, crude protein and crude lipid contents of muscle and liver were significantly affected by dietary protein, but not by dietary lipid level (P > 0.05). The increase in dietary lipid level resulted in an increase in linoleic acid in liver and muscle paralleled with a decrease in n-3 highly unsaturated fatty acids content in muscle of fish. In considering these results, it was concluded that the diet containing 400 g kg-1 protein with 70 g kg-1 lipid level is optimal for growth and efficient feed utilization of juvenile fancy carp.

Keywords: fancy carp, dietary protein, dietary lipid, Cyprinus carpio, fatty acid

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Authors: Rotimi Larayetana, Yahaya Abdulrazaq, Oladunni O. Falola, Abayomi Ajayi

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The aim of this study was to perform green synthesis of silver nanoparticles (AgNPs) with the aqueous extract of Moringa oleifera Lam (M oleifera) leaves and determine its effects on benign prostatic hyperplasia in Wistar rats. Silver nitrate (AgNO₃) solution was reduced using the aqueous extract of Moringa oleifera Lam leaves, the resultant biogenic AgNPs were characterized by Fourier transformed infrared spectrophotometric, SEM, TEM and X-ray diffraction analysis. Animal experiments involved thirty (30) adult male Wistar rats randomly divided into five groups (A to E; n ₌ 5). Group A received only subcutaneous injection of olive oil daily while the other groups got 3 mg/kg/daily of testosterone propionate (TP) subcutaneously plus 50 mg/kg/daily of AgNPs intraperitoneally (B), 3 mg/kg/daily of TP plus 25 mg/kg/daily of AgNPs (C), 3 mg/kg/daily of TP only (D) and 25 mg/kg/daily of AgNPs only (E). The animals were sacrificed after 14 days, and the prostate gland, liver, and kidney were processed for histological analysis. Phytochemical screening and GC-MS analysis were performed to determine the composition of the M oleifera extract used. Biogenic AgNPs with an average diameter of 23 nm were synthesized. Biogenic AgNPs ameliorated hormone-induced prostate enlargement, and the inhibition of prostatic hypertrophy could be due to the presence of a significant amount of plant fatty acids and phytosterols in the aqueous extract of M oleifera extract. However, the administration of biogenic AgNPs at higher doses impacted negatively on the cytoarchitecture of the liver. Green synthesis of AgNPs with the aqueous extract of Moringa oleifera might be beneficial for the treatment of BPH.

Keywords: benign prostatic hyperplasia, biogenic synthesis, Moringa oleifera, silver nanoparticles, testosterone

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Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla

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Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line

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Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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Authors: Thinakar Mani Balusamy, Venkateswaran A. R., Bharat Narasimhan, Ratnakar Kini S., Kani Sheikh M., Prem Kumar K., Pugazhendi Thangavelu, Arun Murugan, Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal, Amit Soni

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Background and Aims: The liver is integral to lipid metabolism, and a compromise in its function leads to perturbations in these pathways. In this study, we hope to determine the correlation between CLD severity and its effect on lipid parameters. We also look at the etiology-specific effects on lipid levels. Materials and Methods: This is a retrospective cross-sectional analysis of 250 patients with cirrhosis compared to 250 healthy age and sex-matched controls. Severity assessment of CLD using MELD and Child-Pugh scores was performed and etiological details collected. A questionnaire was used to obtain patient demographic details and lastly, a fasting lipid profile (Total, LDL, HDL cholesterol, Triglycerides and VLDL) was obtained. Results: All components of the lipid profile declined linearly with increasing severity of CLD as determined by MELD and Child-Pugh scores. Lipid levels were clearly lower in CLD patients as compared to healthy controls. Interestingly, preliminary analysis indicated that CLD of different etiologies had differential effects on Lipid profiles. This aspect is under further analysis. Conclusion: All components of the lipid profile were definitely lower in CLD patients as compared to controls and demonstrated an inverse correlation with increasing severity. The utilization of this parameter as a prognosticating aid requires further study. Additionally, preliminary analysis indicates that various CLD etiologies appear to have specific effects on the lipid profile – a finding under further analysis.

Keywords: CLD, cholesterol, HDL, LDL, lipid profile, triglycerides, VLDL

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Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

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Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

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