Degeneration of retinal neuroblasts by chinoform-ferric chelate

Summary The possible mechanism of neuropathic effect of chinoform was investigated using cultured retinal neuroblasts from chick embryos. Retinal neuroblasts completely degenerated by chinoform-ferric chelate within a day. This change, however, was not observed with free chinoform or ferric ion.a-Tocopherol had a potent protective effect on the toxicity of the chelate. From these results, it was concluded that the lipid peroxidation due to ferric ion chelated with chinoform incorporated into the membrane of nerve tissues is the most important step in induction of the neuropathy.This work was supported in part by a grant from the Ministry of Health and Welfare of Japan.Correspondence should be addressed to K. Yagi, Institute of Biochemistry, Faculty of Medicine, University of Nagoya, Nagoya 466, Japan.     

Formation of lipoperoxide in isolated sciatic nerve by chinoform-ferric chelate.

Effects of chinoform and chinoform-ferric chelate on formation of lipoperoxide in isolated sciatic nerve were investigated. Free chinoform did not increase the lipoperoxide level, while chinoform-ferric chelate significantly increased it. Assuming that the lipoperoxide formed denatures the associated protein in the nerve, the effect of chinoform-ferric chelate could explain, at least partly, the demyelination of nerve tissues caused by massive doses of chinoform.     

Formation of lipoperoxide in isolated sciatic nerve by chinoform-ferric chelate

Summary Effects of chinoform and chinoform-ferric chelate on formation of lipoperoxide in isolated sciatic nerve were investigated. Free chinoform did not increase the lipoperoxide level, while chinoform-ferric chelate significantly increased it. Assuming that the lipoperoxide formed denatures the associated protein in the nerve, the effect of chinoform-ferric chelate could explain, at least partly, the demyelination of nerve tissues caused by massive doses of chinoform.     

Lipid peroxidation caused by chinoform-ferric chelate in cultured neural retinal cells

Incorporation of chinoform-ferric chelate was demonstrable in cultured neural retinal cells of chick embryos after 1 h of incubation, and the lipid peroxide level in the cells was increased strikingly 1 h thereafter. On the other hand, free ferric ions were scarcely incorporated into the cells, and a significant increase in the lipid peroxide level in the cells was not observed. These data indicate that chinoform is carrier of iron for its passage through cell membranes and that the incorporated iron induces lipid peroxidation which in turn leads to neural cell degeneration.     

Lipid peroxidation caused by chinoform-ferric chelate in cultured neural retinal cells

Summary Incorporation of chinoform-ferric chelate was demonstrable in cultured neural retinal cells of chick embryos after 1 h of incubation, and the lipid peroxide level in the cells was increased strikingly 1 h thereafter. On the other hand, free ferric ions were scarcely incorporated into the cells, and a significant increase in the lipid peroxide level in the cells was not observed. These data indicate that chinoform is carrier of iron for its passage through cell membranes and that the incorporated iron induces lipid peroxidation which in turn leads to neural cell degeneration.This work was supported in part by a grant from the Ministry of Health and Welfare of Japan     

Effect of albumin on uncoupling of oxidative phosphorylation by chinoform in rat liver mitochondria.

Addition of serum albumin diminished the uncoupling effect of chinoform on oxidative phosphorylation in rat liver mitochondria. Upon increasing the concentration of magnesium ions in the medium, the action of serum albumin was diminished. These results indicate that serum albumin combines with chinoform in competition with magnesium ions.     

Cadmium-induced changes in avian renal morphology

Summary The effects of i.m. administered cadmium on growth rate and nephromorphology were studied in young pullets. The growth rate of pullets treated with 0.6 mg Cd²⁺/kg at 48-h intervals was severely retarded, reaching only 50% of normal growth by 21 days. Such a decrease in growth rate was prevented when cadmium was given with either ferric or magnesium EDTA chelate. Electron micrographs of kidney tissue from cadmium intoxicated birds revealed massive intracellular disorganisation of proximal tubular cells, showing increased vacuolation and dilated endoplasmic reticulum. Mitochondria were few and swollen with reduced cristae. Some disorganisation was noted in the group treated with MgEDTA in conjunction with cadmium, with normal morphology observed in the group treated FeEDTA plus cadmium.In general, glomerular morphology of intoxicated pullets appeared normal, except that a 25% increase in thickness of the glomerular basement membrane was evident. No such membrane thickening was observed in any of the chelate treated groups.These findings indicate that both chelates can provide certain levels of protection, in terms of growth rate and morphology, from cadmium intoxication. The possible mechanisms by which chelates offer protection have been discussed, but many questions remain unanswered.     

Cadmium-induced changes in avian renal morphology

The effects of i.m. administered cadmium on growth rate and nephromorphology were studied in young pullets. The growth rate of pullets treated with 0.6 mg Cd2+/kg at 48-h intervals was severely retarded, reaching only 50% of normal growth by 21 days. Such a decrease in growth rate was prevented when cadmium was given with either ferric or magnesium EDTA chelate. Electron micrographs of kidney tissue from cadmium intoxicated birds revealed massive intracellular disorganisation of proximal tubular cells, showing increased vacuolation and dilated endoplasmic reticulum. Mitochondria were few and swollen with reduced cristae. Some disorganisation was noted in the group treated with MgEDTA in conjunction with cadmium, with normal morphology observed in the group treated with FeEDTA plus cadmium. In general, glomerular morphology of intoxicated pullets appeared normal, except that a 25% increase in thickness of the glomerular basement membrane was evident. No such membrane thickening was observed in any of the chelate treated groups. These findings indicate that both chelates can provide certain levels of protection, in terms of growth rate and morphology, from cadmium intoxication. The possible mechanisms by which chelates offer protection have been discussed, but many questions remain unanswered.     

A comparative study on the effects of brain extracts and mesodermal membrane extracts on nerve cell differentiation.

Extracts prepared from the mesodermal tissue surrounding the brain stimulate the differentiation of morphologically undifferentiated neuroblasts, while the differentiation of more mature neuroblasts is influenced by brain extracts.     

La glycolyse anaérobie au niveau des lobes optiques isolés de l'embryon de poulet

Summary A series ofin vitro experiments have been made on lactic acid production in anaerobiosis in the developing optic lobes (mesencephalon) of the chick embryo. The rate of anaerobic glycolysis is relatively important during multiplication of the neuroblasts; but, during the differentiation of the neuroblasts into mature neurons, the anaerobic processes are lower than the phosphorylation and oxidation mechanisms essential for the growth of nerve expansions and onset of functional activity.     

Nature of the FeO2 bonding in myoglobin: an overview from physical to clinical biochemistry

The iron(II)-dioxygen bond in myoglobin and hemoglobin is a subject of wide interest. Studies range from examinations of physical-chemical properties dependent on electronic structure, to investigations of stability as a function of oxygen supply. Stability properties are of particular importance in vivo, since the oxygenated form is known to be oxidized easily to the ferric form, which cannot be oxygenated and is therefore physiologically inactive. Kinetic and thermodynamic studies of the stability of native oxymyoglobin have revealed a new feature in FeO2 bonding. In vivo, the iron center is always subject to a nucleophilic attack of the water molecule or hydroxyl ion, which can enter the heme pocket from the surrounding solvent, and thereby irreversibly displace the bound dioxygen from MbO2 in the form of O2- so that the iron is converted to the ferric form. A free energy diagram for the potential reactions of FeO2 visualizes myoglobin as a molecular structure that can provide in solution the delicate balance of kinetic and thermodynamic factors necessary to stabilize reversible oxygenation, as opposed to irreversible autoxidation to metmyoglobin.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Low i.v. doses of cadmium chloride (15 micrograms Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed. It is suggested that the renal changes following the i.v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Vergleichende Untersuchungen über die Toxizität der Ca- und Zn(II)-Chelate der Diäthylentriaminpentaessigsäure

Summary The lethal effect of daily intraperitoneal administrations of Ca-DTPA and Zn(II)-DTPA was studied in mice. Due to recovery processes, single chelate doses are non-additive and the cumulative LD₅₀ increases with decreasing daily dosage. At a given number of administrations, Zn(II)-DTPA is 2.5 times less toxic than Ca-DTPA. However, if the daily dosage is kept constant and the number of administrations variable, Zn(II)-DTPA is 30 times less toxic.     

Cu2+-Adeninring-Wechselwirkung in den Cu2+-Komplexen von Adenosin-5′- und Adenosin-3′-monophosphat

Summary By means of UV and NMR spectroscopy evidence is given for direct interaction between metal ion and heteroaromatic groups in both Cu²⁺-adenosine-5-monophosphate and Cu²⁺-adenosine-3-monophosphate complexes. A comparison with the Cu²⁺-adenosine system shows that this interaction is much enhanced in the monophosphate analogues, which points to the existence of a macrocyclic phosphate-metal-adenine chelate.     

Nature of the FeO2 bonding in myoglobin: An overview from physical to clinical biochemistry

Summary The iron(II)-dioxygen bond in myoglobin and hemoglobin is a subject of wide interest. Studieas range from examinations of physical-chemical properties dependent on electronic structure, to investigations of stability as a function of oxygen supply. Stability properties are of particular importance in vivo, since the oxygenated form is known to be oxidized easily to the ferric form, which cannot be oxygenated and is therefore physiologically inactive.Kinetic and thermodynamic studies of the stability of native oxymyoglobin have revealed a new feature in FeO₂ bonding. In vivo. the iron center is always subject to a nucleophilic attack of the water molecule or hydroxyl ion, which can enter the heme pocket from the surrounding solvent, and thereby irreversibly displace the bound dioxygen from MbO₂ in the form of O ₂ ^– so that the iron is converted to the ferric form. A free energy diagram for the potential reactions of FeO₂ visualizes myoglobin as a molecular structure that can provide in solution the delicate balance of kinetic and thermodynamic factors necessary to stabilize reversible oxygenation, as opposed to irreversible autoxidation to metmyoglobin.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Summary Low i.v. doses of cadmium chloride (15 g Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed.It is suggested that the renal changes following the i. v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Histochemical localization of lactate dehydrogenase in the trout embryo (Salmo irideus, Gibb) during early organogenesis of the cord and the neural tube]

The histochemical study of the LDH in the Trout embryo during the early organogenesis shows a specific localization in notochord cells, in mesodermic cells of the terminal knob and in some prosencephalic neuroblasts. The role of the LDH in the metabolism of NAD as well as in the energetic metabolism of embryonic cells is discussed.     

Effects of ablation of the hindlimb on the organization of the ventral horn of the spinal cord in the lumbar region of green lizard embryos (Lacerta viridis Laur.)]

After extirpation of an hind limb in embryos of Lacerta viridis, numerous motor neuroblasts degenerate on the operated side, in the ventral horn of the lumbar spinal cord and the corresponding motor column is reduced or disappears. The lumbar spinal ganglia are affected and reduced on the operated side.     

Scanning electron microscopy study of spinal cord nerve cells from chick embryos cultured in vitro with poly-L-lysine]

Chick embryo nerve cells from the lumbo-sacral spinal cord have been isolated by trypsinisation and cultivated in Rose chambers on polylysine-L as a substrate. The cells are analysed by scanning electron microscopy. The mode of adherence of these cells to the substrate and the modifications of the surface of the neuroblasts during their transformation into neurocytes are studied.     

Inhibition of paraquat phytotoxicity by a novel copper chelate with superoxide dismutating activity.

A chelate with superoxide dismutase activity, D-penicillamine copper complex, was shown to inhibit paraquat toxicity in flax cotyledons (Linum usitatissimum var. Reina). Paraquat-stimulated chlorophyll loss and ethane production were markedly reduced by this complex. The role of superoxide in the action of paraquat is briefly discussed.