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Biomedical subjects

M Saran

Publications and source records attributed to M Saran.

At least 55 records · Page 3Linked to original sources

Pulse-radiolytic investigations of catechols and catecholamines. II. Reactions of Tiron with oxygen radical species.

Transient spectra and kinetic data of Tiron (1,2-dihydroxybenzene-3,5-disulphonic acid) are reported, obtained after pulse-radiolytic oxidation by hydroxyl radicals (.OH), superoxide anions (O-2) or a combination of both oxygen radicals. The rate constant with .OH radicals was determined at 1.0.10(9) M-1.s-1. Contrary to a previous report (Greenstock, C.L. and Miller, R.W. (1975) Biochim. Biophys. Acta 396, 11--16), the rate constant with O-2 of 1.0.10(7) M-1.s-1 is lower by one order of magnitude; also the semiquinone absorbs at 300 nm rather than at 400 nm. The ratio of the rate constants with .OH and O-2 of 100 again demonstrates that any oxidation reaction by the latter radical is unspecific due to the more efficient reaction of .OH radicals, leading to the same products with catechol compounds.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

On the nature of biochemically generated hydroxyl radicals. Studies using the bleaching of p-nitrosodimethylaniline as a direct assay method.

An efficient scavenger for radiolytically generated hydroxyl (OH) radicals, p-nitrosodimethylaniline, was used to try to substantiate the presence of this oxygen radical species in several biochemical systems. Most of these systems which were investigated had previously been assumed to generate OH radicals, e.g. the autoxidation of 6-hydroxydopamine, the hydroxylating system NADH/phenazine methosulfate, and the oxidation of xanthine or acetaldehyde by xanthine oxidase. We did not observe inhibition of the bleaching of p-nitrosodimethylaniline in oxygenated solutions by other scavengers of OH radicals nor, in the case of xanthine/xanthine oxidase, by catalase and superoxide dismutase. We therefore conclude that, under biochemical conditions as opposed to radiolysis or photolysis, no freely diffusable OH radicals are formed. Rather, a strongly oxidizing OH-analogous complex is considered to represent the p-nitrosodimethylaniline-detectable species formed under these conditions.

Acetaldehyde↗

Oxygen activation in isolated chloroplasts. Mechanism of ferredoxin-dependent ethylene formation from methionine.

Low-potential electron acceptors of photosystem I of chloroplast lamellae produce superoxide anions (0-2) and hydrogen peroxide by autoxidation, but have no effect on ethylene formation from methionine; equimolar amounts of ferredoxin are less active in photosynthetic O-2 and H2O2 production but strongly stimulate ethylene production from methionine. 2. Ten to fifty units of superoxide dismutase inhibit fifty to two hundred units of superoxide dismutase stimulate ethylene formation from methionine by chloroplast lamellae in the presence of ferredoxin. This stimulation is stronger at pH 7.0 than at pH 7.8. Catalase inhibits ethylene formation from methionine. 3. Pulse-radiolytic production of nitrite (NO-2) from hydroxylamine, initiated by hydroxyl radicals (.OH) or O-2, shows no difference in the presence or absence of ferredoxin, nor do the decay kinetics of O2. 4. From the above observations and from model reactions (xanthine/xanthine oxidase; iron salts in the presence of H2O2), it is concluded that reduced ferredoxin in the presence of H2O2 forms a Fenton-type oxidizing species for methionine, generating ethylene in the presence of pyridoxal phosphate. 5. Inhibitory effects of both superoxide dismutase and catalase in oxygen-dependent reactions need not necessarily indicate the participation of the 'Haber-Weiss' reaction.

Chloroplasts↗

The involvement of oxygen radicals during the autoxidation of adrenalin.

1. In unbuffered alkaline solutions, autoxidizing adrenalin generates superoxide anions: both the scavenging by adrenalin itself, leading to adrenochrome, and the formation of nitrite from hydroxylamine are inhibited by superoxide dismutase. No hydroxyl radical could be detected. 2. The yield of hydrogen peroxide increases with pH in a way similar to that of adrenochrome and nitrite. The dissociated form of adrenalin (pK = 8.5) is proposed as the source of superoxide anions. 3. Superoxide dismutase delays rather than inhibits the reaction. In addition to the diminished formation of adrenochrome due to the scavenging of superoxide anions and re-reduction of the semiquinone by hydrogen peroxide, respectively, adrenochrome is further removed by hydrogen peroxide, with final products absorbing at 310 nm. 4. The diminished inhibitory effect of superoxide dismutase above pH 10 is due to superoxide-independent reactions. This effect is masked by the alkaline conversion of adrenochrome to indole compounds. 5. It is concluded that monitoring the absorption of adrenochrome in alkaline solutions does not produce reliable evidence for superoxide anions.

Adrenochrome↗

Pulse-radiolytic investigations of catechols and catecholamines. I. Adrenaline and adrenochrome.

Adrenaline (epinephrine), adrenochrome and C4-substituted catechol model compounds were pulse-irradiated in aqueous neutral and alkaline solutions. Transient spectra are reported after oxidizing adrenaline and reducing adrenochrome. All species appearing during 20 msec interval after the pulse have been identified: the OH adduct with an absorption maximum at 300-310 nm, the semiquinone (at 245 nm), and adrenaline quinone (at 340 nm). The reaction of superoxide anions (O2-) with adrenaline was less efficient, compared with OH radicals. A novel oxidation product, derived from the semiquinone and O2-, has been identified as the 4-hydroxy-3,6-dioxo derivate. The pulse-radiolytic reduction of adrenochrome by hydrated electrons (eaq-) yielded the semiquinone of adrenochrome (absorbing at 470 nm), which subsequently decays by a second-order process. The dismutation products leuco-adrenochrome (absorbing at 300 nm, pH 9-8) and the adrenochrome tautomer (absorbing at 375 nm) are unstable, forming 5,6-dihydro-N-methyl indole and regenerating adrenochrome.

Adrenochrome↗

Superoxide dismutase activity of Cu(Tyr)2 and Cu, Co-erythrocuprein.

Crystalline Cu(Tyr)2 and homogeneous Cu2Co2-erythrocuprein were prepared. The reactivity of each chelated Cu2 compound with superoxide was studied by pulse radiolysis at pH 7.6 +/- 0.1 and compared with the reactivity of native erythrocuprein (superoxide dismutase). Superoxide anions were generated by a 40-ns pulse of 1.81-MeV electrons. The yield of O2 ranged between 6 - 60 muM. The kinetics of the spontaneous O2 decay were second order; in the presence of Cu2 complexes the reaction was first order with respect to O2. Taking into account the effect of the different Cu2 concentrations on the O2 decay, second-order rate constants for the reaction of chelated Cu2 with O2 were obtained. For an equivalent of Cu2 in either erythrocuprein or Cu, Co-erythrocuprein, a numerical value of 1.3 +/- 0.1 x 10(9) M-1S-1 was calculated. Surprisingly, the same value was obtained employing Cu(Tyr)2. The highest rate constant was measured for the hydrated Cu2 (2.7 x 10(9) M-1S-1). In the presence of a biologically significant chelating agent such as serum albumin, a marked decrease in the Cu2aq-induced superoxide dismutation was observed. This was not the case when the dismutation in the presence of either the Cu2 of native erythrocuprein or Cu, Co-erythrocuprein, or those Cu2 ions chelated with tyrosine or certain di- and tripeptides was measured.

Animals↗

Relation of childhood malnutrition to parental education and mothers' nutrition related KAP.

Severely malnourished children (26), weight for age 55.27 +/- 3.17, were identified in a colony of predominantly Muslim urban slum dwellers of low economic status. An equal number of normally nourished children matched for age, sex and per capita income were identified. A strong relation was found between nutritional status of the subjects and educational level of their mothers (P less than 0.025). Father's education was unrelated to childrens' nutritional status. A thirty seven point questionnaire was administered to the mothers to record their nutritional knowledge, attitudes and practices (KAP). Analysis revealed that better KAP in relation to 16 of these 37 questions was not associated with better nutritional status. Seven questions were found to have only a weak association. The remaining 14 questions were identified as important for a nutrition education programme. Comparison of nutritional KAP score based on these 14 questions in case of mothers of normal and severely malnourished children revealed a significantly higher score in the former. Questions related to growth monitoring and breast feeding were not found to be important. No significant association was found between mothers' KAP and educational level. It is concluded that (i) Maternal education and KAP are significantly and independently associated with childrens' nutritional status. (ii) The content areas of knowledge, attitudes and practices significantly associated with nutritional status pertain to nutritional requirements of children, nutritional value of foods, immunisation, hygiene, oral rehydration and diarrhea.

Attitude to Health↗

Radical intermediates during the oxidation of nitropropanes. The formation of NO2 from 2-nitropropane, its reactivity with nucleosides, and implications for the genotoxicity of 2-nitropropane.

The chemistry of the nonenzymatic oxidation of the rat liver carcinogen, 2-nitropropane, and its anionic form, propane-2-nitronate, was investigated using pulse radiolysis and EPR/spin trapping with 3,5-dibromo-4-nitrosobenzenesulfonic acid as the trapping agent. The results suggest that, following initial oxidation to a secondary alkyl radical, propane-2-nitronate is effectively degraded in a peroxidative chain reaction with the intermediary formation of peroxyl and NO2.radicals. The latter radical was shown to react appreciably fast with ribonucleosides, deoxyribonucleosides, and guanosine nucleotides. It is proposed that nonenzymatic formation of NO2.radicals after enzymatic oxidation of propane-2-nitronate to the corresponding secondary alkyl radical accounts for the induction of DNA damage observed after exposure of rats to 2-nitropropane.

Free Radicals↗

Kinetic investigations of the autoxidation of adrenalin.

Generation rates of superoxide anions (O2-) by autoxidizing adrenalin at pH 9.5 were determined in solutions containing either superoxide dismutase (0.85 M-1 S-1) or hydroxylamine (0.0185 M-1 S-1) as competitive scavengers. The rate constants of O2- with adrenalin and hydroxylamine were calculated for neutral and alkaline solutions. The respective values were for adrenalin: 5.6 X 10(4) M-1 S-1, pH 7.8; 7.0 X 10(3) M-1 S-1, pH 9.5--and for hydroxylamine 5.9 X 10(4) M-1 S-1, pH 7.8; 3.4 X 10(4) M-1 S-1, pH 9.5. The effects of various competitors and O2- sources on the rate constants were compared.

Epinephrine↗

Radical functions in vivo: a critical review of current concepts and hypotheses.

Most of the basic knowledge about radical reactions comes from radiation chemical studies in vitro. In view of the rapidly increasing knowledge on radical reaction in vivo, it is important to reconcile the fundamental physico-chemical reaction characteristics of radicals with the need to explain their alleged biological effects. Severe problems in the understanding of their in vivo action remain unsolved. An example is phagocytosis, which seems to be a paradigm of a 'deleterious' radical process. The exact mechanism is not clear; so it is an open question whether the intruder is eventually killed by radicals (like OH) or by endproducts of radical reactions (like H2O2 and/or HOCl). It is even more difficult to understand signalling by radicals: owing to their chemical nature they are 'unspecifically' reacting species--they withdraw or add electrons--and thus their reactions are governed by redox-properties. Since all radicals have different redox characteristics and different molecular shapes, the usual key-and-keyhole picture for molecular interaction does not apply, as there, is no reactive site conceivable which has the property of reacting with radicals 'specifically. Our intent in this article is: (i) to briefly review some fundamental characteristics of in vitro radical reactions, (ii) to extrapolate from this to the conditions in vivo, and (iii) to discuss current hypotheses concerning the redox-regulation of cellular signalling. This leads us to the tentative conclusion that radicals per se must be tolerated by the cell and do not threaten its life, if they stay below a certain concentration limit. The main biological implication of radical-reactions seems to be that the cell derives signals from the balance of oxidative versus reductive processes and that radicals may interact with pathways of intra- and intercellular communication.

Animals↗