ABSTRACT
The cytotoxicity of citrinin was evaluated in an established cell line of baby hamster kidney cells. The primary effect of the mycotoxin was on the adherence of the cells to the culture bottles. Microscopic evaluation of morphological alterations indicated that the cells which were originally elongated and flattened, became swollen and round. Electron microscopic examination showed that citrinin (0.1, 0.5 and 1.0 mM) incubated for 10 hours with cultured cells, promoted drastic alterations of normal mitochondria, with swelling and cell death. Transplasma membrane redox system is inhibited by citrinin (81%). This effect is dependent not only on the toxin concentration, but also on the time of exposure to the cells.
Subject(s)
Citrinin/pharmacology , Kidney/cytology , Animals , Cell Adhesion/drug effects , Cell Membrane/metabolism , Cell Membrane/physiology , Cell Membrane/ultrastructure , Cells, Cultured , Cricetinae , Dose-Response Relationship, Drug , Kidney/drug effects , Kidney/ultrastructure , Microscopy, Electron , Mitochondria/metabolism , Mitochondria/physiology , Mitochondria/ultrastructure , Oxidation-Reduction , Time FactorsABSTRACT
Effect of methotrexate (MTX) on mitochondrial oxygen uptake, oxidative phosphorylation and on the activity of several enzymes linked to respiratory chain was studied. MTX was able to inhibit state III respiration activated by ADP and to decrease the respiratory coefficient with the substrates alpha-ketoglutarate and glutamate; these effects became pronounced when mitochondria were pre-incubated with MTX for 10 min. No effect was observed on ATPase activity of undamaged or broken mitochondria; the same was true for NADH-oxidase, NADH-dehydrogenase, NADH-cytochrome c reductase, succinate oxidase, and cytochrome c oxidase activity. The effect on the steady-state of cytochrome b, as well as, the inhibitory effect on state III of respiration with NAD+-linked substrates, offers a reasonable possibility to suggesting that the inhibition site of MTX could be in a place anterior to cytochrome b region, and not linked to respiratory chain.
Subject(s)
Methotrexate/pharmacology , Mitochondria, Liver/metabolism , Oxidative Phosphorylation/drug effects , Oxygen Consumption/drug effects , Adenosine Triphosphatases/metabolism , Animals , Cytochrome b Group/metabolism , Electron Transport Complex IV/metabolism , In Vitro Techniques , Mitochondria, Liver/drug effects , Multienzyme Complexes/metabolism , NADH Dehydrogenase/metabolism , NADH, NADPH Oxidoreductases/metabolism , Polarography , Rats , Succinate Dehydrogenase/metabolismABSTRACT
Effects of the antiarrhythmic drugs (propranolol, perhexiline maleate, lidoflazine and iproveratril) on energy-linked reactions and on membrane potential were studied. Propranolol, perhexiline maleate and lidoflazine inhibit the ATPase activity of undamaged and broken mitochondria, and of submitochondrial particles. All drugs are inhibitors of either ATP-driven or of succinate-driven reduction of NADP+. The antiarrhythmics promote a decrease in the membrane potential upon energization of the mitochondrial membrane by alpha-ketoglutarate, succinate, or ATP. It was suggested that these drugs have a primary action on the mitochondrial membrane, thus altering the activities of membrane proteins (channels and enzymes).
Subject(s)
Adenosine Triphosphatases/metabolism , Anti-Arrhythmia Agents/pharmacology , Intracellular Membranes/physiology , Mitochondria, Heart/physiology , Submitochondrial Particles/physiology , Animals , Intracellular Membranes/drug effects , Kinetics , Membrane Potentials/drug effects , Mitochondria, Heart/drug effects , Proton-Translocating ATPases/metabolism , Rats , Submitochondrial Particles/drug effectsABSTRACT
The effect of methotrexate, an anti-cancer drug, on carbohydrate metabolism in the isolated perfused rat liver was investigated. Glucose release from endogenous glycogen (glycogenolysis) is strongly activated by methotrexate. The phenomenon shows a well defined concentration dependence: 100% activation occurs at 2.2 X 10(-4) M. Glycolysis and oxygen consumption are only slightly affected.
