The effects of vitamins and selenium mixture against brain tissue induced by d‐galactosamine

Brain damage is a major complication of fulminant hepatic failure. d ‐Galactosamine (d ‐GalN)‐induced liver toxicity causes damage to brain. The effects of vitamins and selenium mixture against d ‐GalN stimulated brain injury were investigated in this study. Sprague‐Dawley female rats aged 2.0‐2.5 months were used for the study. The rats were divided into four categories. A 0.9% NaCl solution was intraperitoneally given to the experimental rats in the first group. Using gavage technique, the second group of animals were subjected to a formulation consisting of 100 mg·kg^?1·day^?1 vitamin C, 15 mg·kg^?1·day^?1 of β‐carotene, 100 mg·kg^?1·day^?1 of α‐tocopherol in addition to 0.2 mg·kg^?1·day^?1 of sodium selenate for 3 days. The third group was given a single dose of d ‐GalN hydrochloride at the concentration of 500 mg·kg^?1 through a saline injection. The final group was given similar concentrations of both the antioxidant combination and d ‐GalN. Tissue samples were collected under ether anesthesia. The rats treated with d ‐GalN showed brain damage; increased myeloperoxidase, catalase, glutathione peroxidase, glutathione‐S‐transferase, lactate dehydrogenase, and superoxide dismutase activities; and decreased glutathione levels. Treatment with vitamins and selenium combination resulted in alleviation of these alterations in the rats. These findings suggest that administration of the vitamins and selenium combination suppresses oxidative stress and protects brain cells from injury induced by d ‐GalN.     

Galangin,a natural flavonoid reduces mitochondrial oxidative damage in streptozotocin-induced diabetic rats

Objective: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats.

Methods: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40?mg?kg^?1 body weight (BW)). Galangin (8?mg?kg^?1 BW) or glibenclamide (600?µg?kg^?1 BW) was given orally daily once for 45 days to both healthy and diabetic rats.

Results: Diabetic rats showed significant (P?P?P?P?P?Conclusion: From the results, we conclude that galangin could maintain liver mitochondrial function in diabetic rats.     

Antioxidant activity and hepatoprotective potential of Hammada scoparia against ethanol-induced liver injury in rats

The present work was aimed at studying the antioxidative activity and hepatoprotective effects of methanolic extract (ME) of Hammada scoparia leaves against ethanol-induced liver injury in male rats. The animals were treated daily with 35 % ethanol solution (4 g?kg^?1?day^?1) during 4 weeks. This treatment led to an increase in the lipid peroxidation, a decrease in antioxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in liver, and a considerable increase in the serum levels of aspartate and alanine aminotransferase and alkaline phospahatase. However, treatment with ME protects efficiently the hepatic function of alcoholic rats by the considerable decrease in aminotransferase contents in serum of ethanol-treated rats. The glycogen synthase kinase-3 β was inhibited after ME administration, which leads to an enhancement of glutathione peroxidase activity in the liver and a decrease in lipid peroxidation rate by 76 %. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of ME. These results strongly suggest that treatment with methanolic extract normalizes various biochemical parameters and protects the liver against ethanol induced oxidative damage in rats.     

Protective effects of antioxidant combination against D‐galactosamine‐induced kidney injury in rats

The protective effects of an antioxidant combination in kidney injury induced by the injection of D‐galactosamine (D‐GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100 mg kg^?1 day^?1), β‐carotene (15 mg kg^?1 day^?1), α‐tocopherol (100 mg kg^?1 day^?1), and sodium selenate (0.2 mg kg^?1 day^?1) for three days orally, (3) rats injected D‐GaIN (500 mg kg^?1) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D‐GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D‐GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D‐GaIN + antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D‐GaIN‐induced kidney injury of rats. Copyright © 2010 John Wiley & Sons, Ltd.     

Antifeedant and cytotoxic activity of gibberellic acid against Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae)

The present study investigates the effect of gibberellic acid (GA3), a terpenoid and phytohormone, on the digestive physiology and intermediary metabolism of the cotton bollworm Helicoverpa armigera Hübner (Lepidoptera, Noctuidae). Incorporation of GA3 (800 μg g^?1 diet) in an artificial diet results in significant reductions in the rates of diet consumption and the efficiency of conversion of food consumption by by H. armigera larvae. The relative growth rate decreases as the concentration increases. The relative α‐amylase activity in sixth‐instar larvae of H. armigera decreases significantly after ingestion of four concentrations of GA3. Histological studies of the midgut in GA3‐treated larvae (800 μg g^?1 diet) show degeneration of the epithelial cells. The alanine and aspartate aminotransferase activity decreases at the highest concentration. However, acid phosphatase, alkaline phosphatase, γ‐glutamyl transferase and lactate dehydrogenase activity increase significantly compared with the control. The results clearly demonstrate the adverse effects of GA3 on H. armigera via interruption of nutritional physiology and metabolism.     

Influence of kolaviron and vitamin E on ethylene glycol monoethyl ether‐induced haematotoxicity and renal apoptosis in rats

The present study investigated the protective effects of kolaviron, a biflavonoid from the seed of Garcinia kola, and vitamin E on ethylene glycol monoethyl ether (EGEE)‐induced haematotoxicity and renal apoptosis in male rats. EGEE was administered at a dose of 200 mg kg^?1 alone or simultaneously administered with kolaviron (100 and 200 mg kg^?1) and vitamin E (50 mg kg^?1) for 14 days. Results of haematological examination showed that white blood cells, platelets, neutrophils and mean corpuscular haemoglobin concentration were significantly lower, whereas lymphocytes were increased in EGEE‐exposed rats compared with those in the control. Administration of EGEE caused a significant decrease in the superoxide dismutase and catalase activities as well as in the glutathione level but significantly increased glutathione Stransferase activity and levels of hydrogen peroxide and lipid peroxidation in kidneys of rats compared with those in the control. Also, EGEE‐treated rats showed significant elevation in the serum urea and creatinine with marked increase in the frequency of terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling assay‐positive apoptotic cells in the tubular epithelial cells in comparison with the control. Co‐administration with kolaviron or vitamin E exhibited chemoprotective effects against EGEE‐mediated haematotoxicity, augmented renal antioxidant status and prevented the induction of renal apoptosis. Copyright © 2013 John Wiley & Sons, Ltd.     

Protective effects of ascorbic acid on hepatotoxicity and oxidative stress caused by carbon tetrachloride in the liver of Wistar rats

This study was planned to investigate the protective effect of l (+)‐ascorbic acid (Vit C) on CCl₄‐induced hepatotoxicity and oxidative stress in the liver of Wistar rats (Rattus Norvegicus, strain Wistar). Twenty‐four adult male Wistar rats were fed with standard rat chow diet for 10 days and randomly were divided into four groups of six each as follows: (1) control, (2) CCl₄, (3) “CCl₄ + Vit C”, (4) Vit C groups. CCl₄ was applied to rats belonging to CCl₄ and “CCl₄ + Vit C” groups subcutaneously at 1 mg kg^?1 dose CCl₄ for 3 days. Vit C applied to “CCl₄ + Vit C” and “Vit C” group rats intraperitoneally at 300 mg kg^?1 dose for 3 days. All rats were sacrificed and livers were quickly removed on the fourth day of the experiment. MDA, total glutathione (T.GSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐PX) activities were measured in the liver of all groups of rats and also serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were detected to determine liver functions in all groups of rats. Histopathological changes were evaluated by light and transmission electron microscopes. In “CCl₄ + Vit C” group, MDA level was significantly decreased (p < 0.05) and SOD, CAT, GSH‐PX activities were significantly increased (p < 0.005, 0.01, 0.05) respectively, T.GSH level was significantly increased (p < 0.005) and serum ALT and AST activities were significantly decreased (p < 0.01, 0.05), respectively, when compared with CCl₄ group. These results show that Vit C has a highly protective effect on hepatotoxicity and oxidative stress caused by CCl₄. Copyright © 2009 John Wiley & Sons, Ltd.     

The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats

Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory activities in different conditions. The goal of this study was to evaluate the effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received 0.2 mL kg^?1 dose of NS intraperitoneally daily throughout 14 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS treated rats' tissue levels of total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and catalase (CAT) levels were statistically significant in the NS treated rats compared to BDL group (p < 0.01 for both). On the other hand, administration of NS in the rats with biliary obstruction resulted in inhibition of necro‐inflammation. These results indicate that NS exerts a therapeutic effect on cholestatic liver injury in bile duct ligated rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. Copyright © 2009 John Wiley & Sons, Ltd.     

Alanine Aminotransferase and Aspartate Aminotransferase in Leishmania tarentolae1

SYNOPSIS. Culture stages (promastigotes) of Leishmania tarentolae were tested for alanine aminotransferase (E.C.2.6.1.2) and aspartate aminotransferase (E.C.2.6.1.1.). Neither enzyme was detected in crude cell extracts. After starch block electrophoresis, however, both transaminase activities were found in proteins migrating toward the anode. Only one species of each enzyme was found. Using coupled enzyme assay systems, the following physical and kinetic properties were seen: 1) aspartate aminotransferase was inhibited by α-ketoglutarate concentrations above 1.68 × 10^?2 M and alanine aminotransferase was inhibited by concentrations higher than 1.34 × 10^?2 M; 2) the Michaelis constant (Km[α-ketoglutarate]) was 5.4 × 10^?4 M for aspartate aminotransferase and 3.0 × 10^?4 M for alanine aminotransferase; 3) maximum activity was found at ?pH 8.5 (broad range between pH 7.75–9.0) for aspartate aminotransferase whereas maximum activity for alanine aminotransferase was ?pH 7.2 (range between pH 7.0–7.5); 4) both enzymes lost half of their activity after 4 days at 8 C; 5) aspartate aminotransferase was most active at 35 C and completely inactivated at 59.5 C, alanine aminotransferase exhibited maximum activity at 29.5 C and was completely inactivated at 61 C; and 6) neither enzyme showed enhanced activity with added pyridoxal phosphate.     

DEVELOPMENT OF MITOCHONDRIAL PYRUVATE METABOLISM IN RAT BRAIN

The activities of a number of mitochondrial enzymes involved in the metabolism of pyruvate during development of the rat brain were investigated. The rates of decarboxylation of [1-¹⁴C]pyruvate to ¹⁴CO₂ via pyruvate dehydrogenase and the fixation of H¹⁴CO₃^? in the presence of pyruvate via pyruvate carboxylase by brain homogenates were very low in newborn rats. These rates increased markedly by about four-fold and 15-fold respectively during 10–35 postnatal days. The rates of the fixation of H¹⁴CO₃^? by cerebral homogenates were supported by the development of the activity of pyruvate carboxylase in rat brain. The activities of citrate synthase, aconitase, NAD-malate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and phosphoenol-pyruvate carboxykinase were very low in the particulate fraction of the newborn rat brain. The activities of all these enzymes increased makedly by about three- to 10-fold during 10–35 days after birth. The activity of mitochondrial phosphoenolpyruvate carboxykinase from rat brain was not precipitated by an antibody prepared against rat liver cytosolic phosphoenolpyruvate carboxykinase suggesting that cerebral mitochondrial enzyme is immunologically different from that of the cytosolic form in hepatocytes. The significance of the development of the cerebral mitochondrial metabolism is discussed in relation to biochemical maturation of the brain.     

Pyruvate metabolism in rice coleoptiles under anaerobiosis

Relative importance of ethanolic, lactate and alanine fermentation pathways was estimated in coleoptiles of rice seedlings (Oryza sativa L.) subjected to anoxic stress. The in vitro activities of alcohol dehydrogenase (ADH, EC 1.1.1.1), pyruvate decarboxylase (PDC, EC 4.1.1.1) and alanine aminotransferase (AlaAT, EC 2.6.1.2) in the coleoptiles increased in anoxia, whereas no significant increase was measured in lactate dehydrogenase (LDH, EC 1.1.1.27) activity. At 48 h, the ADH, PDC and AlaAT activities in anoxic coleoptiles were 62-, 15- and 7.6-fold greater, respectively, than those in the presence of oxygen. Ethanol and alanine in the coleoptiles accumulated rapidly under anoxia, increasing by 48 h, 57- and 5.6-fold compared with those in the presence of oxygen, respectively. However, lactate concentration did not increase and no initial burst of lactate production was detected. The relative ratio of carbon flux from pyruvate to ethanol, lactate and alanine in anoxic coleoptiles was estimated to be 92, 1 and 7% of the total carbon flux, respectively. These results suggest that the potential carbon flux from pyruvate to ethanol may be much greater than the potential flux from pyruvate to lactate and alanine in rice coleoptiles during anoxia.     

T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice

The effect of T-5224, a selective inhibitor of c-Fos/activator protein (AP)-1, on lipopolysaccharide (LPS) induced liver injury was examined in mice. Administration of LPS (10?mg?kg^?1, i.p.) markedly increased serum levels of tumor necrosis factor-alpha (TNFα), high mobility group box 1 (HMGB1), alanine aminotransferase/aspartate aminotransferase (ALT/AST), liver tissue levels of macrophage-inflammatory protein-1 alpha (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1), as well as hepatic necrosis and inflammation, leading to 67?% lethality. Administration of T-5224 (300?mg?kg^?1, p.o.) after intraperitoneal injection of LPS imparted appreciable protection against acute elevations in serum levels of TNFα, HMGB1, ALT/AST as well as in liver tissue levels of MIP-1α and MCP-1, and reduced the lethality (27?%). These data indicate that T-5224 ameliorates liver injury and improves survival through decreasing production of proinflammatory cytokines and chemokines in endotoxemic mice.     

Metabolism of amino acids in germinating yellow lupin seeds. II. Pathway of conversion of aspartate to alanine during the imbibition

The incorporation of ¹⁴C-aspartate during the imbibition of yellow lupin seeds resulted in the production of ¹⁴C-alanine and ¹⁴CO₂. On the basis of tracer and enzymatic assays, conducted in vitro on the extract obtained from lupin seeds, it is postulated that aspartate can be converted to oxaloacetate, then, by phosphoenolopyruvate and pyruvate to alanine. This pathway can be catalyzed by the following enzymes: aspartate aminotransferase, phosphoenolpyruvate carboxykinase, pyruvate kinase and alanine aminotransferase.     

Protective effect of cannabidiol against cadmium hepatotoxicity in rats

The protective effect of cannabidiol, the non-psychoactive component of Cannabis sativa, against liver toxicity induced by a single dose of cadmium chloride (6.5 mg kg^?1 i.p.) was investigated in rats. Cannabidiol treatment (5 mg kg^?1/day, i.p.) was applied for five days starting three days before cadmium administration. Cannabidiol significantly reduced serum alanine aminotransferase, and suppressed hepatic lipid peroxidation, prevented the depletion of reduced glutathione and nitric oxide, and catalase activity, and attenuated the elevation of cadmium level in the liver tissue resulted from cadmium administration. Histopathological examination showed that cadmium-induced liver tissue injury was ameliorated by cannabidiol treatment. Immunohistochemical analysis revealed that cannabidiol significantly decreased the cadmium-induced expression of tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, caspase-3, and caspase-9, and increased the expression of endothelial nitric oxide synthase in liver tissue. It was concluded that cannabidiol may represent a potential option to protect the liver tissue from the detrimental effects of cadmium toxicity.     

Pyruvate metabolism in Helicobacter pylori

The metabolism of pyruvate by Helicobacter pylori was investigated employing one- and two-dimensional ¹H and ¹³C nuclear magnetic resonance spectroscopy. Generation of pyruvate from l-serine in incubations with whole cell lysates indicated the presence of serine dehydratase activity in the bacterium. Pyruvate was formed also in cell suspensions and lysates from phosphoenol pyruvate. Metabolically competent cells incubated aerobically with pyruvate yielded alanine, lactate, acetate, formate, and succinate. The production of alanine and lactate indicated the presence of alanine transaminase and lactate dehydrogenase activities, respectively. Accumulation of acetate and formate as metabolic products provided evidence for the existence of a mixed-acid fermentation pathway in the microorganism. Formation of succinate suggested the incorporation of the pyruvate carbon skeleton into the Kreb's cycle. Addition of pyruvate to various liquid culture media did not affect bacterial growth or loss of viability. The variety of products formed using pyruvate as the sole substrate showed the important role of this metabolite in the energy metabolism of H. pylori.     

Neonatal exposure to bisphenol A advances pubertal development in female rats

Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague‐Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg^?1·day^?1 BPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg^?1·day^?1 BPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg^?1·day^?1 BPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg^?1·day^?1 dose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg^?1·day^?1, neonatal exposure to BPA may affect pubertal development in a dose‐dependent manner.     

Cd AND Zn TOLERANCE AND ACCUMULATION BY SEDUM JINIANUM IN EAST CHINA

Field survey, hydroponic culture, and pot experiments were carried out to examine and characterize cadmium (Cd) and zinc (Zn) uptake and accumulation by Sedum jinianum, a plant species native to China. Shoot Cd and Zn concentrations in S. jinianum growing on a lead/Zn mine area reached 103–478 and 4165–8349 mg kg^?1 (DM), respectively. The shoot Cd concentration increased with the increasing Cd supply, peaking at 5083 mg kg^?1 (DM) when grown in nutrient at a concentration of 100 μmol L^?1 for 32 d, and decreased as the solution concentration increased from 200 to 400 μmol L^?1. The shoot-to-root ratio of plant Cd concentrations was > 1 when grown in solution Cd concentrations ≤ 200 μmol L^?1. Foliar, stem, and root Zn concentrations increased linearly with the increasing Zn level from 1 to 9600 μmol L^?1. The Zn concentrations in various plant parts decreased in the order roots > stem > leaves, with maximum concentrations of 19.3, 33.8, and 46.1 g kg^?1 (DM), respectively, when plants were grown at 9600 μmol Zn L^?1 for 32 d. Shoot Cd concentrations reached 16.4 and 79.8 mg kg^?1 (DM) when plants were grown in the pots of soil with Cd levels of 2.4 mg kg^?1 and 9.2 mg kg^?1, respectively. At soil Zn levels of 619 and 4082 mg kg^?1, shoot Zn concentrations reached 1560 and 15,558 mg kg^?1 (DM), respectively. The results indicate that S. jinianum is a Cd hyperaccumulator with a high capacity to accumulate Zn in the shoots.     

Alanine production in an H+-ATPase- and lactate dehydrogenase-defective mutant of Escherichia coli expressing alanine dehydrogenase

Previously, we reported that pyruvate production was markedly improved in TBLA-1, an H⁺-ATPase-defective Escherichia coli mutant derived from W1485lip2, a pyruvate-producing E. coli K-12 strain. TBLA-1 produced more than 30 g/l pyruvate from 50 g/l glucose by jar fermentation, while W1485lip2 produced only 25 g/l pyruvate (Yokota et al. in Biosci Biotechnol Biochem 58:2164–2167, 1994b). In this study, we tested the ability of TBLA-1 to produce alanine by fermentation. The alanine dehydrogenase (ADH) gene from Bacillus stearothermophilus was introduced into TBLA-1, and direct fermentation of alanine from glucose was carried out. However, a considerable amount of lactate was also produced. To reduce lactate accumulation, we knocked out the lactate dehydrogenase gene (ldhA) in TBLA-1. This alanine dehydrogenase-expressing and lactate dehydrogenase-defective mutant of TBLA-1 produced 20 g/l alanine from 50 g/l glucose after 24 h of fermentation. The molar conversion ratio of glucose to alanine was 41%, which is the highest level of alanine production reported to date. This is the first report to show that an H⁺-ATPase-defective mutant of E. coli can be used for amino acid production. Our results further indicate that H⁺-ATPase-defective mutants may be used for fermentative production of various compounds, including alanine.     

Effect of envenomation on enzymes of brain of albino rats

Effects of high doses of cobra venom, (150 micrograms/120 +/- 20 g body wt) and viper venom (300 micrograms/120 +/- 20 g body wt) on aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), acetylcholinesterase (ACh) and alkaline phosphatase (ALP) of brain of albino rats were studied. While AST, LDH, ACh and ALP activities increased in both viper and cobra venom treated rats, ALT decreased in both groups compared to control.