Permeability Of Rat Liver Mitochondria Research Articles

Action of Oroxylin to Membrane Permeability of Rat Liver Mitochondria

Action of Oroxylin to Membrane Permeability of Rat Liver Mitochondria

Effect of Dequalinium on Respiration and the Inner Membrane Permeability of Rat Liver Mitochondria

The effect of the lipophilic penetrating cation dequalinium on rat liver mitochondria was studied. It was found that dequalinium dose-dependently inhibits the respiration rate of rat liver mitochondria in ADP-stimulated (V3) and DNP-stimulated (uncoupled) states. This can be due to the fact that dequalinium is a potent inhibitor of complex III of the mitochondrial respiratory chain. It was shown that dequalinium induces a high-amplitude swelling of rat liver mitochondria. The dequalinium-induced swelling of the organelles depends on the presence of inorganic phosphate in the incubation medium: in the absence of phosphate or in the presence of the phosphate carrier inhibitor mersalyl in the phosphate-containing medium, no swelling of the mitochondria was observed. At low concentrations of dequalinium (≤10 μM), this swelling is inhibited by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. At the same time, at high concentrations of dequalinium (>10 μM), cyclosporin A becomes ineffective. It was found that in the presence of dequalinium the rate of the H2O2 production increased in rat liver mitochondria. Possible mechanisms of toxic effect of dequalinium chloride are discussed.

Withdrawal period for Elancoban® for chickens for fattening, chickens reared for laying and turkeys for fattening - Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed.

EFSA JournalVolume 6, Issue 7 730 OpinionOpen Access Withdrawal period for Elancoban® for chickens for fattening, chickens reared for laying and turkeys for fattening - Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 09 July 2008 https://doi.org/10.2903/j.efsa.2008.730Citations: 2 Panel members: Georges Bories, Paul Brantom, Joaquim Brufau de Barberà, Andrew Chesson, Pier Sandro Cocconcelli, Bogdan Debski, Noël Dierick, Anders Franklin, Jürgen Gropp, Ingrid Halle, Christer Hogstrand, Joop de Knecht, Lubomir Leng, Anne-Katrine Lundebye Haldorsen, Alberto Mantovani, Miklós Mézes, Carlo Nebbia, Walter Rambeck, Guido Rychen, Atte von Wright and Pieter Wester Acknowledgement: The European Food Safety Authority wishes to thank the members of the Working Group on Coccidiostats for the preparation of this opinion. Adoption date: 18 June 2008 Published date: 9 July 2008 Question number: EFSA-Q-2007-140 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Davison, K.L., 1984. Monensin Absorption and Metabolism in Calves and Chickens. J. Agr. Food Chem. 32, 1273– 1277. Dimenna, G.P., Lyon, F.S., Thompson, F.M., Creegan, J.A. and Wright, G.J., 1989. Effect of antibiotic combination, dosing period, dose vehicle, and assay method on salinomycin residue levels and their ionophoricity in chicken tissues. J. Agr. Food Chem. 37, 668– 676. Donoho, A.L., Herberg, R.J., Zornes L.L. and Van Duyn R.L., 1982. Excretion and tissue distribution of 14C monensin in chickens. J. Agr. Food Chem. 30, 909– 913. Donoho, A.L., 1984. Biochemical Studies on the Fate of Monensin in Animals and in the environment. J. Anim. Sci. 58, 1528– 1539. EC (European Commission), 1979. Report of the Scientific Committee for Animal Nutrition (SCAN) on the use of Monensin Sodium and Flavophospholipol in feedingstuffs for fattening cattle. <ec.europa.eu/food/fs/sc/oldcomm6/antibiotics/28_en.pdf> EC (European Commission), 1981. Report of the Scientific Committee for Animal Nutrition (SCAN) on the use of Monensin Sodium in feedingstuffs for poultry. <ec.europa.eu/food/fs/sc/oldcomm6/antibiotics/26_en.pdf> EC (European Commission), 1983. Report of the Scientific Committee for Animal Nutrition (SCAN) on the use of Monensin Sodium in feedingstuffs for turkeys. <ec.europa.eu/food/fs/sc/oldcomm6/antibiotics/27_en.pdf> EFSA (European Food Safety Authority), 2004. Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the request of the Commission on the reevaluation of coccidiostat Elancoban® in accordance with article 9G of Council Directive 70/524/EEC. <www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620783743.htm> EFSA (European Food Safety Authority), 2006a. Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the Maximum Residue Limits for monensin sodium for chickens and turkeys for fattening. <www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620781970.htm> EFSA (European Food Safety Authority), 2006b. Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the safety and efficacy of the coccidiostat Elancoban® (monensin sodium) as a feed additive for calves for rearing and cattle for fattening in accordance with Regulation (EC) No 1831/2003. <www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620782650.htm> EMEA (European Medicines Agency), 2007. MONENSIN (Cattle, including dairy cows) EMEA/CVMP/185123/2007-Final. <www.emea.europa.eu/pdfs/vet/mrls/Monensin.pdf> Estrada-O, S., Rightmire, B. and Lardy, H., 1968. Antibiotics as tools for metabolic studies. XI. Specific inhibition of ion transport in mitochondria by the monensins. Antimicrob. Agents Chemother. 7, 279– 88. Godfrey, M.A.J., Luckey, M.F. and Kwasowski, P., 1997. IAC/cELISA detection of monensin elimination from chicken tissues following oral therapeutic dosing. Food Add. Contam. 3, 281– 286. Henri, J., Chéneau, E., Diop, M., Abjean, J-P., Roudaut, B., Sanders, P. and Laurentie, M., 2006. Monensin residues and bioavailability studies to develop a physiologically based pharmacokinetic (PBPK) model in chicken. Tenth International Congress of the European Association for Veterinary Pharmacology and Toxicology (Torino, Italy). Submitted by AFSSA (Agence française de sécurité sanitaire des aliments). Pressman, B.C., 1968. Ionophorous antibiotics as models for biological transport. Fed. Proc. 27, 1283– 1288. Wong, D.T., Horng, J.S., Hamil, R.L. and Lardy, H.A., 1971. Effect of a new monocarbocyclic acid antibiotic, A204, on the monovalent cation permeability of rat liver mitochondria. Biochem. Pharmacology. 20, 3169– 3177. Citing Literature Volume6, Issue7July 2008730 ReferencesRelatedInformation

Inhibitors of the ATP/ADP antiporter suppress stimulation of mitochondrial respiration and H + permeability by palmitate and anionic detergents

The action of ATP/ADP-antiporter inhibitors upon the uncoupling effect of palmitate, detergents and ‘classical’ uncouplers has been studied. The uncoupling effect was estimated by stimulation of succinate oxidation and of H + permeability of rat liver mitochondria in the presence of oligomycin. It is shown that carboxyatractylate (CAtr) and pyridoxal 5-phosphate (PLP) suppress the uncoupling induced by palmitate and the anionic detergents SDS and cholate, but do not affect that induced by the cationic detergents CTAB, by the non-ionic detergent Triton X-100, as well as by the ‘classical’ uncouplers FCCP and DNP. The results are discussed in terms of a concept assuming that the ATP/ADP-antiporter facilitates the electrophoretic export of hydrophobic anions from mitochondria.

Thyroid hormone effects on the proton permeability of rat liver mitochondria

The effect of thyroid status on passive permeability of liver mitochondrial inner membrane was studied in euthyroid (EU), hyperthyroid (HYPER), hypothyroid (HYPO) rats and hypothyroid rats treated with a single dose of 3,3',5-triiodothyronine (HYPO + T 3. Respiration was titrated with uncoupler and plotted against uncoupler concentration to calculate proton permeability. The passive permeability was the same in EU, HYPER, and HYPO + T 3 rats, but was significantly lower in HYPO mitochondria. The State IV respiration rates were the same as the oligomycin-inhibited rats for EU, HYPO and HYPO + T 3 rats, but in HYPER rats the oligomycin rate was less than the State IV rate. The data show that hypothyroid mitochondria have decreased permeability of the inner membrane which can be normalized by a single dose of T 3. Hyperthyroid mitochondria show increased oligomycin-sensitive ATPase activity in State IV, a possible mechanism of the enhanced respiratory rate.

Evidence of changes, induced by HeNe laser irradiation, in the optical and biochemical properties of rat liver mitochondria

Photoacoustic spectroscopy measurements reveal that HeNe low-power irradiation causes changes in mitochondrial optical properties. However, it has been found that this process damages neither the membrane of the mitochondria nor some of their enzymatic activities. The HeNe laser irradiation effect was investigated both with regard to the redox state change of intramitochondrial pyridine nucleotides, induced by addition to the mitochondria of oxaloacetate, oxoglutarate plus ammonia and cis-aconitate, and to the permeability of rat liver mitochondria to the same substrates. It was found that laser irradiation modifies some NADH-linked dehydrogenase reactions of the mitochondria.

Evidence of changes, induced by HeNe laser irradiation, in the optical and biochemical properties of rat liver mitochondria

Abstract Photoacoustic spectroscopy measurements reveal that HeNe low-power irradiation causes changes in mitochondrial optical properties. However, it has been found that this process damages neither the membrane of the mitochondria nor some of their enzymatic activities. The HeNe laser irradiation effect was investigated both with regard to the redox state change of intramitochondrial pyridine nucleotides, induced by addition to the mitochondria of oxaloacetate, oxoglutarate plus ammonia and cis-aconitate, and to the permeability of rat liver mitochondria to the same substrates. It was found that laser irradiation modifies some NADH-linked dehydrogenase reactions of the mitochondria.

Selective permeability of rat liver mitochondria to purified malate dehydrogenase isoenzymes in vitro.

1. The mitochondrial malate dehydrogenase from rat liver has been purified to a state of homogeneity as judged by starch-gel electrophoresis and the cytoplasmic isoenzyme has been obtained in a partically purified state. 2. Inhibition of the isoenzymes by sulphite has been studied. 3. In mitochondria loaded with sulphite, the catalytic activity of the (partially inhibited) internal malate dehydrogenase has been measured by addition of oxaloacetate to the suspension medium and observation of the consequent decrease in fluorescence of NADH. 4. Addition of mitochondrial malate dehydrogenase to suspensions of mitochondria loaded with sulphite resulted in an increase in the level of intramitochondrial enzymic activity as measured by the above technique. Addition of the cytoplasmic isoenzyme did not result in such an increase. 5. These results show that mitochondria in suspension are permeable to the mitochondrial malate dehydrogenase but not to the cytoplasmic isoenzyme. 6. This conclusion has been confirmed by direct measurement of a decrease of enzyme activity in solution and an increase inside the mitochondria after incubation of organelles in solutions containing mitochondrial malate dehydrogenase. No such effect was observed with the cytoplasmic isoenzyme. 7. Some features of the permeation process have been studied.

Effects of halothane on mitochondrial ion permeability

The previously reported effects of halothane to inhibit the mitochondrial oxidation of NAD-linked substrates, enhance the rate of succinate oxidation, and stimulate ATPase activity, suggest an action similar to that of agents which uncouple oxidative phosphorylation. Since it is likely that uncoupling agents facilitate transmembrane proton transport, the effects of halothane on the permeability of rat liver mitochondria were investigated. Halothane (2 mM) induced passive mitochondrial swelling in isotonic sodium nitrate and potassium chloride. Concentrations greater than 8.3 mM induced very rapid swelling, but much higher concentrations (20 mM) were necessary to produce swelling in sucrose. This tends to support the concept that some of the effects of halothane may be secondary to a direct effect on membranes.

Selective permeability of rat liver mitochondria to purified aspartate aminotransferases in vitro.

1. A method was devised to allow determination of intramitochondrial aspartate amino-transferase activity in suspensions of intact mitochondria. 2. Addition of purified rat liver mitochondrial aspartate aminotransferase to suspensions of rat liver mitochondria caused an apparent increase in the intramitochondrial enzyme activity. No increase was observed when the mitochondria were preincubated with the purified cytoplasmic isoenzyme. 3. These results suggest that mitochondrial aspartate aminotransferase, but not the cytoplasmic isoenzyme, is able to pass from solution into the matrix of intact rat liver mitochondria in vitro. 4. This system may provide a model for studies of the little-understood processes by which cytoplasmically synthesized components are incorporated into mitochondria in vivo.

Permeability of rat liver mitochondria to leucine, tyrosine, α-aminoisobutyric acid, and lysine

Radioactive tracer studies show that l-leucine is rapidly taken up by isolated rat liver mitochondria. There is an initial rapid uptake of l-leucine during the first 30 sec of incubation, followed by a slower, progressive increase in l-leucine accumulation over a 10-min incubation. d-Leucinc penetrates the mitochondria rapidly but does not accumulate inside. Both the d and l isomers of tyrosine penetrate the mitochondria relatively more slowly, equilibration being achieved only after several minutes of incubation. The synthetic amino acid, α-aminoisobutyric acid, is shown to rapidly enter the mitochondria. This amino acid is not accumulated within the mitochondria. l-Lysine, a positively charged amino acid, exhibits uptake characteristics similar to those of l-leucine. An examination of the energetic requirements for these amino acid transfer processes reveals no dependence on metabolic energy or on gradients of inorganic cations, and no effects of several reagents known to block other transport mechanisms, under the conditions tested. These findings and previously reported observations are consistent with the view that the membranes of rat liver mitochondria contain a number of different mechanisms mediating uptake of various amino acids.

Effect of a new monocarboxylic acid antibiotic, A204, on the monovalent cation permeability of rat liver mitochondria

A newly isolated polyether monocarboxylic acid antibiotic, A204, is reported here to affect the translocation of monovalent cations across mitochondrial membrane. At 1 μM, A204 caused a complete inhibition of glutamate oxidation in valinomycin or monazomycin-treated rat liver mitochondria in a K + medium. The antibiotic has the following ion specificity: K + = Rb +>Na + = Cs +>Li +. Pyridine nucleotides in intact mitochondria became oxidized upon addition of A204; however, A204 did not affect respiration supported by succinate oxidation. It also causes the leakage of K +, transient release of H +, and decrease of mitochondrial volume. The monovalent cation-dependent hydrolysis of ATP in valinomycin- or monazomycin-treated mitochondria was first activated and then inhibited at concentrations of A204 above 2 μM. The inhibitory effect of A204 on adenosine triphosphatase (ATPase) is also ion dependent, but it is equally supported by Na +, K + and Rb +. We can therefore classify A204 as a new ionophore with properties shared by its predecessors, monensin, nigericin and dianemycin, which induce ion permeability in biological membranes.

The effects of colloids on the appearance and substrate permeability of rat liver mitochondria.

The electron microscopic appearance of rat liver mitochondria fixed in glutaraldehyde is altered if certain colloids (serum albumin, dextran or Ficoll) are present in the medium at about 3%. To compare behaviour in control and albumin-supplemented media, the rate of stimulated respiration was measured with various substrates. It was found that the rate of respiration was reduced with succinate or pyruvate and was almost abolished with oxoglutarate, while malate oxidation (in presence of glutamate) was unaffected. The rate of oxoglutarate oxidation could be restored by causing mitochondrial swelling. It is suggested that the effects are due to the presence of endogenous colloids in the particles whose effects on water activity have to be balanced by external colloid. In the absence of external colloid, swelling of the internal colloid-containing compartments may give rise to an enhanced permeability of the membrane so that reactions occurin vitro which do not take place rapidly if at allin vivo.

Permeability of rat liver mitochondria to α-ketoglutarate, antipyrine, and carnitine

The study of the permeability of rat liver mitochondria under conditions supporting oxidative phosphorylation compares the uptake of 14C-labeled α-ketoglutarate, antipyrine and carnitine by mitochondria incubated briefly at 0 ° and those incubated up to 90 min at 30 ° Uptake is measured in pellets produced by centrifugation in the cold. The α-ketoglutarate was incubated in the presence of malonate with mitochondria in which oxygen consumption was followed with an oxygen electrode. Less than 4% of the isotope equivalent to the amount of substrate oxidized remains with the unwashed pellets. Antipyrine uptake appears to be the same at 0 ° and at 30 °, and is greater than would be predicted if simple diffusion were responsible; adsorption to the mitochondrial membranes is indicated. The uptake of carnitine is enhanced at the higher temperature and is greater in mitochondria carrying out oxidative phosphorylation than in those suspended in 0.25 m sucrose. The extent to which these compounds can be removed from the pellets by washing with isotonic sucrose varies.