Search results for: Malate dehydrogenase-glutamate oxaloacetate aminotransferase
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 17

Search results for: Malate dehydrogenase-glutamate oxaloacetate aminotransferase

17 New Malate Dehydrogenase-Glutamate Oxaolacetate Aminotransferase Glutamate Oxaloacetate Aminotransferase Enzyme System from Cereals and its Bioengineering Application

Authors: Zhanar S. Kudiyarova, Zhanar K. Rakhmetova, L. K. Bekbayeva, N. Z. Omirbekova, M. K. Gilmanov

Abstract:

Malate dehydrogenase-glutamate oxaloacetate aminotransferase (MDh-GOAT) enzyme complex (the EC) was isolated and purified from wheat and rise, their some main physicchemical properties were studied. Michael-s constants of the EC MDh-GOAT to malate, glutamate and NAD were investigated. This kinetic results show a high relationship to glutamate. Taking into account important role of the the EC in catabolism of glutamate – the central amino acid of a nitric exchange, there is a sharp necessity of deeper studying of this enzyme complex. Therefore the basic purpose of the work is studying the basic physical and chemical properties of this enzyme complex discovered by us, which would be very important for understanding the mechanisms of reaction catalyzed by the EC.

Keywords: Malate dehydrogenase-glutamate oxaloacetate aminotransferase, enzyme complex, glutamate.

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16 Biochemical Changes in the Liver of Mice after Exposure to Different Doses of Diclofenac Sodium

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: Anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde.

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15 The Effect of Glucogenic and Lipogenic Diets on Blood Metabolites of Baloochi Sheep

Authors: Alireza Vakili, Ali Mortezaee, Mohsen Danesh Mesgaran

Abstract:

The aim of present study was to assess the effect of glucogenic (G) and lipogenic (L) diets on blood metabolites in Baloochi lambs. Three rumen cannulated Baloochi sheep were used as a 3×3 Latin square design with 3 periods (28 days). Experimental diets were a glucogenic, a lipogenic and a mixture of G and L diets (50:50). The animals were fed diets consisted of 50% chopped alfalfa hay and 50% concentrate. Diets were fed once daily ad libitum. Blood samples were taken from jugular vein before the feeding, 2, 4 and 6 hour post feeding at day 27. Results indicated that β- hydroxybutyrate (BHBA), glucose, insulin and aspartate aminotransferase (AST) were not affected by treatments (P > 0.05). However, lipogenic diet increased significantly activity of Alanine aminotransferase (ALT) and concentration of non-esterified fatty acid (NEFA) in blood plasma (P < 0.05)

Keywords: glucogenic, lipogenic, blood metabolites

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14 Evaluation of Some Prominent Biomarkers in Rural Type – 2 Diabetes Mellitus Cases in Kanyakumari District, Tamil Nadu, India

Authors: Murugan. A., Jerlin Nirmala. F .

Abstract:

Life is beautiful. But, it is decided by genes, environment and the individual and shattered by the natural and / or the invited problems. Most of the global rural helpless masses are struggling for their survival since; they are neglected in all aspects of life including health. Amidst a countless number of miserable diseases in man, diabetes is becoming a dreaded killer and ramifying the entire globe in a jet speed. Diabetes control continues as a Herculean task to the scientific community and the modern society in the 21st century also. T2DM is not pertaining to any age and it can develop even during the childhood. This multifactorial disease abruptly changes the activities of certain vital biomarkers in the present rural T2DM cases. A remarkable variation in the levels of biomarkers like AST, ALT, GGT, ALP, LDH, HbA1C, C- peptide, fasting sugar, post-prandial sugar, sodium, potassium, BUN, creatinine and insulin show the rampant nature of T2DM in this physically active rural agrarian community.

Keywords: Alanine aminotransferase, Aspartate aminotransferase, Blood urea nitrogen, Glycated haemoglobin, Thyroid stimulating hormone

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13 Influence of Hydrocarbons on Plant Cell Ultrastructure and Main Metabolic Enzymes

Authors: T. Sadunishvili, E. Kvesitadze, M. Betsiashvili, N. Kuprava, G. Zaalishvili, G. Kvesitadze

Abstract:

Influence of octane and benzene on plant cell ultrastructure and enzymes of basic metabolism, such as nitrogen assimilation and energy generation have been studied. Different plants: perennial ryegrass (Lolium perenne) and alfalfa (Medicago sativa); crops- maize (Zea mays L.) and bean (Phaseolus vulgaris); shrubs – privet (Ligustrum sempervirens) and trifoliate orange (Poncirus trifoliate); trees - poplar (Populus deltoides) and white mulberry (Morus alba L.) were exposed to hydrocarbons of different concentrations (1, 10 and 100 mM). Destructive changes in bean and maize leaves cells ultrastructure under the influence of benzene vapour were revealed at the level of photosynthetic and energy generation subcellular organells. Different deviations at the level of subcellular organelles structure and distribution were observed in alfalfa and ryegrass root cells under the influence of benzene and octane, absorbed through roots. The level of destructive changes is concentration dependent. Benzene at low 1 and 10 mM concentration caused the increase in glutamate dehydrogenase (GDH) activity in maize roots and leaves and in poplar and mulberry shoots, though to higher extent in case of lower, 1mM concentration. The induction was more intensive in plant roots. The highest tested 100mM concentration of benzene was inhibitory to the enzyme in all plants. Octane caused induction of GDH in all grassy plants at all tested concentrations; however the rate of induction decreased parallel to increase of the hydrocarbon concentration. Octane at concentration 1 mM caused induction of GDH in privet, trifoliate and white mulberry shoots. The highest, 100mM octane was characterized by inhibitory effect to GDH activity in all plants. Octane had inductive effect on malate dehydrogenase in almost all plants and tested concentrations, indicating the intensification of Trycarboxylic Acid Cycle. The data could be suggested for elaboration of criteria for plant selection for phytoremediation of oil hydrocarbons contaminated soils.

Keywords: Higher plants, hydrocarbons, cell ultrastructure, glutamate and malate dehydrogenases.

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12 Assessment of Diagnostic Enzymes as Indices of Heavy Metal Pollution in Tilapia Fish

Authors: Justina I. R. Udotong

Abstract:

Diagnostic enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined as indices of heavy metal pollution in Tilapia guinensis. Three different sets of fishes treated with lead (Pb), iron (Fe) and copper (Cu) were used for the study while a fourth group with no heavy metal served as a control. Fishes in each of the groups were exposed to 2.65mg/l of Pb, 0.85mg/l of Fe and 0.35 mg/l of Cu in aerated aquaria for 96 hours. Tissue fractionation of the liver tissues was carried out and the three diagnostic enzymes (AST, ALT, and ALP) were estimated. Serum levels of the same diagnostic enzymes were also measured. The mean values of the serum enzyme activity for ALP in each experimental group were 19.5±1.62, 29.67±2.17 and 1.15±0.27 IU/L for Pb, Fe and Cu groups compared with 9.99±1.34 IU/L enzyme activity in the control. This result showed that Pb and Fe caused increased release of the enzyme into the blood circulation indicating increased tissue damage while Cu caused a reduction in the serum level as compared with the level in the control group. The mean values of enzyme activity obtained in the liver were 102.14±6.12, 140.17±2.06 and 168.23±3.52 IU/L for Pb, Fe and Cu groups, respectively compared to 91.20±9.42 IU/L enzyme activity for the control group. The serum and liver AST and ALT activities obtained in Pb, Fe, Cu and control groups are reported. It was generally noted that the presence of the heavy metal caused liver tissues damage and consequent increased level of the diagnostic enzymes in the serum.

Keywords: Diagnostic enzymes, enzyme activity, heavy metals, tissues investigations.

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11 Effect of Oral Administration of “Gadagi“ Tea on Liver Function in Rats

Authors: A. M. Gadanya, M. S. Sule, M. K. Atiku

Abstract:

Effect of oral administration of “Gadagi" tea on liver function was assessed on 50 healthy male albino rats which were grouped and administered with different doses(mg/kg) i.e low dose (380mg/kg, 415mg/kg, 365mg/kg, 315mg/kg for “sak", “sada" and “magani" respectively), standard dose ( 760mg/kg, 830mg/kg, 730mg/kg for “sak-, “sada" and “magani" respectively) and high dose (1500mg/kg, 1700mg/kg and 1460mg/kg for “sak--,"sada" and “magani" groups respectively) for a period of four weeks. Animals that were not administered with the tea constituted the control group. At the end of fourth week, the animals were sacrificed and their serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and globulins (GLO) were determined. Mean serum ALT and ALP activities were significantly higher (P<0.05) in rats orally administered with high dose of “sak" and those administered with standard dose of “sada" than those of the control group, suggesting a probable impairment of liver function due to liver cytolysis.Mean serum AST, ALT and ALP activities were significantly lower (P<0.05) in rats that were orally administered with high dose of “magani" than that of the control group, suggesting a probable improvement in liver function (due to decrease in liver cytolysis). Mean serum TP, ALB and GLO levels were significantly higher (P<0.05) in rats that were orally administered with the various doses of“sak", “sada" and “magani" than those of the control group. This also suggests a probable improvement in the synthetic function of the liver.Thus, some dosages of “sak" and “sada could be hepatotoxic, whereas “magani" especially at the high dose administered could have pharmacologically positive effect on the liver of the rats.

Keywords: Gadagi" tea, Liver function, Oral, Rats.

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10 Effect of the Ethanolic Leaf Extract of Ficus exasperata on Biochemical Indices of Albino Mice Experimentally Infected with Plasmodium berghei (NK 65)

Authors: Lebari B. Gboeloh

Abstract:

Ficus exasperata is a plant used in the traditional management of malaria in south-south Nigeria. An investigation into the effects of the ethanolic extract of the leaf of the plant on some biochemical indices in albino mice infected with Plasmodium berghei (NK 65) was conducted. 48 mice with weight range of 13-23 g were grouped into six (A, B, C, D, E, and F). Each group contained 8 mice. Groups A, B, C, D and E were infected with blood containing the parasite. Group F was not infected and served as the normal control. On the 6th day after infection, 4 mice from each group were sacrificed and blood samples are collected for investigation. The remaining mice in each group were treated. Mice in Groups A, B and C were administered orally with 200, 300 and 500 mg/kg body weight of Ficus exasperata respectively for six days. Group D was not treated while Group F was given distilled water. Group E was treated with 5 mg/kg body weight of chloroquine. On the 6th day post treatment, these mice were sacrificed and blood samples were collected for biochemical analysis. The results indicated that on the 6th day post inoculation, the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) in all the mice infected with the parasite were significantly (p < 0.05) elevated. However, on the 6th day post administration of extract, the increased levels of AST, ALP and ALT were significantly (p < 0.05) reduced in groups administered with 300 and 500 mg/kg body weight of the extract compared with groups D and F. The reduction in the levels of these enzymes is an indication that F. exasperata have no hepatotoxic effect on the mice at the dose levels administered.

Keywords: Ficus exasperata, albino mice, Plasmodium berghei, biochemical parameters.

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9 Hepatoprotective Activity of Sharbat Deenar, against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Authors: Nazmul Huda, Ashik Mosaddik, Abdul Awal, Shafiqur Rahman, Rukhsana Shaheen, Mustofa Nabi

Abstract:

Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl4) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl4 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl4 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl4 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.

Keywords: Carbon tetrachloride, Hepatoprotective, Sharbat Deenar, Silymarin.

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8 Influence of Pomegranate (Punica granatum L.) on Dimethoate Induced Hepatotoxicity in Rats

Authors: Abou-Baker Salim, A. A. K. Abou-Arab, Sherif R. Mohamed, T. A. Eldesouky

Abstract:

Pomegranate (Punica granatum L.) is an ancient fruit of great medical interest and rich source of antioxidants. Pesticides as dimethoate play a crucial role in the occurrence many diseases in plants, animal and human. Therefore the ability of Pomegranate (Punica granatum L.) to alleviate hepatotoxicity induced by organophosphate pesticide dimethoate was investigated. Albino male rats were divided randomly into 4 groups and kept at 7 animals per group in an environmentally controlled condition for 6 weeks. The first group was served as a control group (basal diet), the second group fed on basal diet supplemented with 5% freeze dried pomegranate seeds, the third group fed on 20 ppm dimethoate contaminated diet and the last group fed on dimethoate contaminated diet supplemented with 5% freeze dried pomegranate seeds. The results revealed that administration of dimethoate caused high significant increased in liver functions: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities as well as lipid peroxide (malonaldhyde, MDA); on the other hand high significant decreased on glutathione (GSH), glutathione peroxidase (GPx), albumin and total protein were observed. However addition of 5% freeze dried pomegranate seeds significantly improved all previously mentioned parameters. These results indicate the dimethoate induced hepatotoxicity and highlight the protective effect of pomegranate seeds as a potential protective agent against dimethoate induced hepatotoxicity. This may be attributed to the powerful antioxidants (polyphenols, total phenols, and total flavonoids) which present in high levels in pomegranate as well as improving the immunity by activation of antioxidant enzymes GSH and GPx.

Keywords: Pomegranate, organophosphate pesticides, dimethoate, liver toxicity, free radicals, antioxidants.

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7 Toxicological and Histopathological Studies on the Effect of Tartrazine in Male Albino Rats

Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer

Abstract:

Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD50) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Keywords: Albino rats, tartrazine, toxicity, pathology

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6 Links between Inflammation and Insulin Resistance in Children with Morbid Obesity and Metabolic Syndrome

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Obesity is a clinical state associated with low-grade inflammation. It is also a major risk factor for insulin resistance (IR). In its advanced stages, metabolic syndrome (MetS), a much more complicated disease which may lead to life-threatening problems, may develop. Obesity-mediated IR seems to correlate with the inflammation. Human studies performed particularly on pediatric population are scarce. The aim of this study is to detect possible associations between inflammation and IR in terms of some related ratios. 549 children were grouped according to their age- and sex-based body mass index (BMI) percentile tables of WHO. MetS components were determined. Informed consent and approval from the Ethics Committee for Clinical Investigations were obtained. The principles of the Declaration of Helsinki were followed. The exclusion criteria were infection, inflammation, chronic diseases and those under drug treatment. Anthropometric measurements were obtained. Complete blood cell, fasting blood glucose, insulin, and C-reactive protein (CRP) analyses were performed. Homeostasis model assessment of insulin resistance (HOMA-IR), systemic immune inflammation (SII) index, tense index, alanine aminotransferase to aspartate aminotransferase ratio (ALT/AST), neutrophils to lymphocyte (NLR), platelet to lymphocyte, and lymphocyte to monocyte ratios were calculated. Data were evaluated by statistical analyses. The degree for statistical significance was 0.05. Statistically significant differences were found among the BMI values of the groups (p < 0.001). Strong correlations were detected between the BMI and waist circumference (WC) values in all groups. Tense index values were also correlated with both BMI and WC values in all groups except overweight (OW) children. SII index values of children with normal BMI were significantly different from the values obtained in OW, obese, morbid obese and MetS groups. Among all the other lymphocyte ratios, NLR exhibited a similar profile. Both HOMA-IR and ALT/AST values displayed an increasing profile from N towards MetS3 group. BMI and WC values were correlated with HOMA-IR and ALT/AST. Both in morbid obese and MetS groups, significant correlations between CRP versus SII index as well as HOMA-IR versus ALT/AST were found. ALT/AST and HOMA-IR values were correlated with NLR in morbid obese group and with SII index in MetS group, (p < 0.05), respectively. In conclusion, these findings showed that some parameters may exhibit informative differences between the early and late stages of obesity. Important associations among HOMA-IR, ALT/AST, NLR and SII index have come to light in the morbid obese and MetS groups. This study introduced the SII index and NLR as important inflammatory markers for the discrimination of normal and obese children. Interesting links were observed between inflammation and IR in morbid obese children and those with MetS, both being late stages of obesity.

Keywords: Children, inflammation, insulin resistance, metabolic syndrome, obesity.

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5 Cannabidiol Treatment Ameliorates Acetaminophen-Induced Hepatotoxicity in Mice

Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

Abstract:

The possible therapeutic effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against acute hepatotoxicity induced by a single oral dose of acetaminophen (500mg/kg) in mice. Cannabidiol (two intraperitoneal injections, 5mg/kg, each) was given 1 hour and 12 hours following acetaminophen administration. Acetaminophen administration caused significant elevations of serum alanine aminotransferase, and hepatic malondialdehyde, and nitric oxide levels, and a significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters resulted from acetaminophen administration. Also, histopathological examination showed that cannabidiol markedly attenuated ameliorated acetaminophen-induced liver tissue damage. These results emphasize that cannabidiol represents a potential therapeutic option to protect against acetaminophen hepartotoxicity which is a common clinical problem.

Keywords: cannabidiol, acetaminophen, liver, mice.

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4 Higher Plants Ability to Assimilate Explosives

Authors: G. Khatisashvili, M. Gordeziani, G. Adamia, E. Kvesitadze, T. Sadunishvili, G. Kvesitadze

Abstract:

The ability of agricultural and decorative plants to absorb and detoxify TNT and RDX has been studied. All tested 8 plants, grown hydroponically, were able to absorb these explosives from water solutions: Alfalfa > Soybean > Chickpea> Chikling vetch >Ryegrass > Mung bean> China bean > Maize. Differently from TNT, RDX did not exhibit negative influence on seed germination and plant growth. Moreover, some plants, exposed to RDX containing solution were increased in their biomass by 20%. Study of the fate of absorbed [1-14ðí]-TNT revealed the label distribution in low and high-molecular mass compounds, both in roots and above ground parts of plants, prevailing in the later. Content of 14ðí in lowmolecular compounds in plant roots are much higher than in above ground parts. On the contrary, high-molecular compounds are more intensively labeled in aboveground parts of soybean. Most part (up to 70%) of metabolites of TNT, formed either by enzymatic reduction or oxidation, is found in high molecular insoluble conjugates. Activation of enzymes, responsible for reduction, oxidation and conjugation of TNT, such as nitroreductase, peroxidase, phenoloxidase and glutathione S-transferase has been demonstrated. Among these enzymes, only nitroreductase was shown to be induced in alfalfa, exposed to RDX. The increase in malate dehydrogenase activities in plants, exposed to both explosives, indicates intensification of Tricarboxylic Acid Cycle, that generates reduced equivalents of NAD(P)H, necessary for functioning of the nitroreductase. The hypothetic scheme of TNT metabolism in plants is proposed.

Keywords: Higher plants, TNT, RDX, transformation.

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3 Protective Effect of Hesperidin against Cyclophosphamide Hepatotoxicity in Rats

Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

Abstract:

The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Keywords: Cyclophosphamide, hesperidin, liver, rats.

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2 Protein Profiling in Alanine Aminotransferase Induced Patient cohort using Acetaminophen

Authors: Gry M, Bergström J, Lengquist J, Lindberg J, Drobin K, Schwenk J, Nilsson P, Schuppe-Koistinen I.

Abstract:

Sensitive and predictive DILI (Drug Induced Liver Injury) biomarkers are needed in drug R&D to improve early detection of hepatotoxicity. The discovery of DILI biomarkers that demonstrate the predictive power to identify individuals at risk to DILI would represent a major advance in the development of personalized healthcare approaches. In this healthy volunteer acetaminophen study (4g/day for 7 days, with 3 monitored nontreatment days before and 4 after), 450 serum samples from 32 subjects were analyzed using protein profiling by antibody suspension bead arrays. Multiparallel protein profiles were generated using a DILI target protein array with 300 antibodies, where the antibodies were selected based on previous literature findings of putative DILI biomarkers and a screening process using pre dose samples from the same cohort. Of the 32 subjects, 16 were found to develop an elevated ALT value (2Xbaseline, responders). Using the plasma profiling approach together with multivariate statistical analysis some novel findings linked to lipid metabolism were found and more important, endogenous protein profiles in baseline samples (prior to treatment) with predictive power for ALT elevations were identified.

Keywords: DILI, Plasma profiling, PLSDA, Randomforest.

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1 Snails and Fish as Pollution Biomarkers in Lake Manzala and Laboratory B: Lake Manzala Fish

Authors: Hanaa M. M. El-Khayat, Hanan S. Gaber, Hoda Abdel-Hamid, Kadria M. A. Mahmoud, Hoda M. A. Abu Taleb

Abstract:

This work aimed to examine Oreochromis niloticus fish from Lake Manzala in Port Said, Dakahlya and Damietta governorates, Egypt, as a bio-indicator for the lake water pollution through recording alterations in their hematological, physiological, and histopathological parameters. All fish samples showed a significant increase in levels of alkaline phosphatase (ALP), creatinine and glutathione-S-transferase (GST); only Dakahlya samples showed a significant increase (p<0.01) in aspartate aminotransferase (AST) level and most Dakahlya and Damietta samples showed reversed albumin and globulin ratio and a significant increase in γ-glutamyltransferase (GGT) level. Port-Said and Damietta samples showed a significant decrease of hemoglobin (Hb) while Dakahlya samples showed a significant decrease in white blood cell (WBC) count. Histopathological investigation for different fish organs showed that Port-Said and Dakahlya samples were more altered than Damietta. The muscle and gill followed by intestine were the most affected organs. The muscle sections showed severe edema, neoplasia, necrotic change, fat vacuoles and splitting of muscle fiber. The gill sections showed dilated blood vessels of the filaments, curling of gill lamellae, severe hyperplasia, edema and blood vessels congestion of filaments. The intestine sections revealed degeneration, atrophy, dilation in blood vessels and necrotic changes in sub-mucosa and mucosa with edema in between. The recorded significant alterations, in most of the physiological and histological parameters in O. niloticus samples from Lake Manzala, were alarming for water pollution impacts on lake fish community, which constitutes the main diet and the main source of income for the people inhabiting these areas, and were threatening their public health and economy. Also, results evaluate the use of O. niloticus fish as important bio-indicator for their habitat stressors.

Keywords: Lake Manzala, Oreochromis niloticus fish, water pollution, physiological, hematological and histopathological parameters.

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