The effects of Tl(+) ions on isolated rat liver mitochondria were studied in the presence of nonactin, a cyclic ionophore. Nonenergized rat liver mitochondria were increasingly swollen at an elevated concentration of Tl(+) in the 160 mOsm medium containing 0-150 mM sucrose and 0-75 mM TlNO(3) or 0-50 mM Tl acetate. On the contrary, mitochondria in experiments with nonactin were contracted in the medium with 5-25 mM Tl(+) and were swollen only in the medium with 50-75 mM TlNO(3) or 50 mM Tl acetate. State 4 respiration along with swelling of succinate-energized mitochondria followed contraction after their deenergization was further enhanced at increasing concentration of Tl acetate in a medium containing nonactin. Regardless of the presence of nonactin, State 3 and 2,4-dinitrophenol (DNP)-stimulated respiration and the monoamine oxidase (MAO) activity were not affected in the medium with 0-25 mM Tl acetate and sucrose. DNP-stimulated respiration decreased and the MAO activity somewhat increased in the medium containing 50 mM Tl acetate and nonactin. Uptake of (86)Rb(+) by energized mitochondria in the presence of valinomycin was considerably decreased when Tl(+) and nonactin were simultaneously present in the medium. An increase of the toxic effect of Tl(+) on rat liver mitochondria in the presence of nonactin is accounted for by disruption of mitochondria due to their more extensive swelling and uncoupling of mitochondria, resulting in the stimulation of State 4 and depletion of their energy store.
We studied action of inorganic phosphate (P(i)) on toxic effects of Tl+ in isolated rat liver mitochondria. This is a convenient model to study the toxicity of heavy metals. P(i) markedly retarded contraction of energized mitochondria swollen in the TlNO3 medium and even stronger stimulated swelling and state 4 of succinate-energized mitochondria in the TlNO3 medium. A valinomycin-induced decrease of K+-diffusion potential was also accelerated by Tl+ in the presence of P(i). The mitochondrial permeability transition pore in the medium containing Ca2+, TlNO3, and nitrates of univalent cations was distinctly stimulated by P(i). However, P(i) did not affect both the Tl+-stimulated swelling of nonenergized mitochondria in the TlNO3 medium and swelling of energized mitochondria in the Tl acetate medium. Respiration stimulated by 2,4-dinitrophenol and monoamine oxidase activity of energized mitochondria were not affected by Tl+ regardless of the presence of P(i). We suggested that stimulation by P(i) of toxic action of Tl+ in mitochondria and cells could be due to even greater enhancement of uncoupling of mitochondria as shown by an additional increase of swelling and state 4, and in the greater probability of opening of MPTP in the presence of P(i) and Ca2+.
No abstract
A key direction in the search for and designing of new prophylactic tools edible herbs rich in biologically active compounds [1]. For example, a group of preparations based on metal derivatives of chlorophyll has been extensively studied in the past years. These preparations, on the one hand, can compensate for the deficiency of one or another microelement in the body; on the other hand, they exhibit various biological activities [1][2][3]. To this end, or great interest is tsinkovit, a zinccontaining derivative of chlorophyll, which allows compensate for zinc deficiency in the body, which may cause may prepathological and pathological conditions [1,4].However, to make a decision to introduce tsinkovit in practice, with regard for its complex chemical composition, a comprehensive experimental study of the mechanism of its action and possible toxic properties should be performed. It should be emphasized that studies of the effect of this preparation on the enzymes involved in metabolism of neurotransmittersmonoamine oxidase (MAO) and acetylcholinesterase (ACE)-have not been performed earlier. It is known that MAO and ACE are the key enzymes in metabolism of endogenous amines, where they implement mediator and regulatory functions, and in the system of cholinergic nerve impulse transmission in the brain and muscles [5,6]. The constancy of ACE activity is essential for the maintenance of normal functioning of the body [5]. It was shown that some effectors, such as organophosphorous and carbamate compounds, sharply decrease ACE activity in different sections of the brain [5]. An increase in ACE activity is observed in poisoning with cocaine [7] and heavy metals [8] and in emotional stress [9]. The data on MAO activity derangement in different pathologies are very important for modern medicine [6].In view of this, we studied the effect of doses of tsinkovit on MAO and ACE activity in three brain sections-the striatum, hypothalamus, and medulla-and MAO activity in the liver and kidneys.The effect of different doses of tsinkovit was studied with male Wister rats weighing 180-200 g. Animals were divided into five groups: four experimental and one control (24 animals in each group). Animals of all groups were kept under equal conditions and received the same balanced diet. Rats of experimental groups received tsinkovit daily with food up to one month at doses of 0.75, 7.5, 100, and 500 mg/kg. Animals of the experimental and control groups (eight animals in each group) were decapitated 10, 20, and 30 days after the beginning of the experiment. Immediately after decapitation, the liver and kidneys were extracted. After opening the skull, and three sections of the brain (the striatum, hypothalamus, and medulla) were extracted as well. Extracted tissues were immediately frozen and stored in a refrigerator at -4°C for 1-2 days. To study the activity of ACE, brain tissues were homogenized in a glass homogenizer in nice volumes (w/v) of 0.05 M sodium-potassium phosphate buffer (pH 7.4) (1 : 9 w/v). Before measuring ACE activity,...
Results obtained from complex medical-physiological investigations performed during 10 scientific expeditions in the Arkhangel'sk Region in 2003-2005 are presented. The effects of climatological-geographic, biogeochemical, and social conditions of the conditions obtaining in the Far North region of Russia on sexual maturation, formation of the structural-functional organization of the brain, autonomic functions, and immunological and biochemical status of schoolchildren were studied using state-of-the-art neurophysiological methods (computerized electroencephalography, computerized rheoencephalography, computerized electric dipole origin tomography, etc.), psychophysiological and psychometric methods (assessment of the state of cognitive and memory functions, Wechsler intellectual scale), along with biochemical assay of monoamine oxidase (MAO, the key enzyme in adrenergic neurotransmitter metabolism) and the liver enzyme butyrylcholinesterase (BuChE) and physicochemical analysis of the levels of macroelements and trace elements in the body.
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