Delta aminolevulinate dehydratase (ALA-D) activity in human and experimental diabetes mellitus

Fernandez-Cuartero, B.; Rebollar, J.; Batlle, Alcira; Salamanca, Rafael Enrı́quez de

doi:10.1016/s1357-2725(98)00145-9

Cited by 44 publications

(32 citation statements)

References 43 publications

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“…To the best of our knowledge, this is the first time that acute exposure to CCl 4 is related to δ-ALA-D inhibition. Accordingly, persuasive evidence has indicated that δ-ALA-D is extremely sensitive to the presence of pro-oxidant agents (Nogueira et al, 2003;Fachinetto et al, 2006), which oxidize -SH groups essential for the enzyme activity (Fernandez-Cuartero et al, 1999;Folmer et al, 2003). Repeated doses of (PhSe) 2 did not alter the inhibitory effect of CCl 4 in δ-ALA-D activity.…”

Section: Discussionmentioning

confidence: 99%

“…Persuasive evidence has indicated that δ-ALA-D is extremely sensitive to the presence of pro-oxidant agents (Nogueira et al, 2003;Fachinetto et al, 2006), which oxidize -SH groups essential for the enzyme activity (Fernandez-Cuartero et al, 1999). Since this enzyme is very sensitive to xenobiotics, δ-ALA-D activity was used as a marker of toxicity.…”

Section: D-aminolevulinate Dehydratase (D-ala-d) Activitymentioning

confidence: 99%

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Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

Nogueira

Borges²,

Souza³

2008

J of Applied Toxicology

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Section: Discussionmentioning

confidence: 99%

Section: D-aminolevulinate Dehydratase (D-ala-d) Activitymentioning

confidence: 99%

Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

Nogueira

Borges²,

Souza³

2008

J of Applied Toxicology

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“…[33][34][35] Recent persuasive evidence from ours as well as other laboratories has indicated that d-ALA-D is extremely sensitive to oxidative stress and possibly to the free radicals which produce it. [36][37][38][39] As pointed out above, buffers can modify AA auto-oxidation, possibly by changing the concentration or redox state of transition metals in the medium and also by scavenging reactive oxygen species such as HO • . 40) The aim of the present study was to investigate both the mechanisms of d-ALA-D inhibition caused by AA as well as the protection afforded by MOPS buffer. Here we propose that d-ALA-D inhibition is mediated by the oxidation of -SH groups caused by the autooxidation of AA, which is catalysed by contaminating metals or another oxidizing system present in liver supernatants and not by the reactive oxygen species formed during AA autoxidation.…”

mentioning

confidence: 99%

Oxidation of .DELTA.-ALA-D and DTT Mediated by Ascorbic Acid: Modulation by Buffers Depends on Free Iron

Rocha

Lissner

Puntel

et al. 2005

Biological & Pharmaceutical Bulletin

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Special attention has been given to reducing agents that can interfere in oxidative and reductive processes, particularly in pathological situations that favour the production of pro-oxidants. One of the most important endogenous reducing agents is ascorbic acid (AA). [1][2][3] This physiological antioxidant participates in a variety of cellular events, including the synthesis of collagen, carnitine, and neurotransmitters, the transformation of xenobiotics, the absorption of iron and the scavenging of oxygen free radicals. [4][5][6][7][8][9][10][11] In vitro, AA can act as a potent oxidant agent particularly in the presence of free metals such as iron and copper. [12][13][14][15] It is reported that AA promotes degradative modifications in other proteins in vitro, in part by the formation of reactive oxygen species during its oxidation. [16][17][18] Of particular importance, AA and H 2 O 2 , in the presence of catalytic amounts of iron-EDTA, react to form HO • , which is extremely reactive and toxic to biological systems. [19][20][21][22][23][24][25] In a previous preliminary study using Fenton's reaction to produce hydroxyl radicals we observed that AA inactivates d-aminolevulinate dehidratase (d-ALA-D) and that the inhibitory action of AA was considerably decreased when 3-morpholinepropanesulfonic acid buffer (MOPS) was used in the d-ALA-D activity assay instead of potassium phosphate buffer (PB). The generation of radicals can affect the thiol groups of proteins. [26][27][28] d-ALA-D is a sulfhydryl-containing enzyme which catalyses the asymmetric condensation of two molecules of d-aminolevulinic acid (d-ALA) to porphobilinogen. [29][30][31] This condensation occurs via the formation of two successive Schiff-base intermediates and porphobilinogen is the precursor of the porphyrins. 32) Consequently, d-ALA-D activity is fundamental for oxidative metabolism. [33][34][35] Recent persuasive evidence from ours as well as other laboratories has indicated that d-ALA-D is extremely sensitive to oxidative stress and possibly to the free radicals which produce it. [36][37][38][39] As pointed out above, buffers can modify AA auto-oxidation, possibly by changing the concentration or redox state of transition metals in the medium and also by scavenging reactive oxygen species such as HO • . 40) The aim of the present study was to investigate both the mechanisms of d-ALA-D inhibition caused by AA as well as the protection afforded by MOPS buffer. Here we propose that d-ALA-D inhibition is mediated by the oxidation of -SH groups caused by the autooxidation of AA, which is catalysed by contaminating metals or another oxidizing system present in liver supernatants and not by the reactive oxygen species formed during AA autoxidation. This hypothesis was confirmed studying dithiothreitol (DTT) oxidation, as a model of the essential enzyme thiols. MATERIALS AND METHODS5-5Ј-Dithio-bis(2-nitrobenzoic) acid (DTNB), dithiothreitol (DTT), ascorbic acid (AA), iron sulfate, ethilenediamintetraacetic acid (EDTA), 3-morpholinepropanesu...

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“…δ-ALA-D is an enzyme inhibited in pro-oxidant situations (Fernandez-Cuartero et al 1999;Santos et al 2005a;) and is an important indicator of organochalcogen (Nogueira et al 2003a) and xenobiotic toxicity (Santos et al 2005a). Compounds that oxidize -SH groups have long been known as potent δ-ALA-D inhibitors; so the inhibition of δ-ALA-D activity could result in accumulation of its substrate, aminolevulinic acid (ALA), which could cause pro-oxidant effects (Barbosa et al 1998;.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one

et al. 2012

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The aim of the present study was to evaluate the potential pharmacological and toxicological properties of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one (compound 1), an organoselenium compound. In vitro experiments showed that compound 1 presented a reduction in the lipid peroxidation induced by Fe²⁺ in thiobarbituric acid-reactive species (TBARS) production, and in the generation of reactive species caused by Fe²⁺/malonate in DCFH-DA oxidation. The high dose (500 mg/kg) induced an increase on ALT but not on AST activity. Hepatic, but not cerebral, δ-ALA-D activity from mice treated with 500 mg/kg presented a significant inhibition. Brain catalase activity was significantly inhibited by 100 mg/kg whereas hepatic catalase activity showed a significant increase at all doses. Hepatic lipid peroxidation was diminished only at lowest dose (100 mg/kg) whereas for brain tissue, all doses induced a significant reduction in TBARS levels. Brain and liver ascorbic acid contents were increased only at highest dose of compound 1. Urea and creatinine levels were not significantly altered by treatments. This is a promising compound with antioxidant activity and low toxicity, suggesting the potential beneficial activity of compound 1 against oxidative damage in many parameters studied in rats and mice.

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Delta aminolevulinate dehydratase (ALA-D) activity in human and experimental diabetes mellitus

Cited by 44 publications

References 43 publications

Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

Oxidation of .DELTA.-ALA-D and DTT Mediated by Ascorbic Acid: Modulation by Buffers Depends on Free Iron

Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one

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