Indole and its alkyl‐substituted derivatives protect erythrocyte and DNA against radical‐induced oxidation

The antioxidant properties of 1,2,3,4‐tetra‐hydrocarbazole, 6‐methoxy‐1,2,3,4‐tetrahydrocar‐bazole (MTC), 2,3‐dimethylindole, 5‐methoxy‐2,3‐dimethylindole, and indole were investigated in the case of hemolysis of human erythrocytes and oxidative damage of DNA induced by 2,2′‐azobis(2‐amidinopropane hydrochloride) (AAPH), respectively. The aim of this work was to explore the influence of methoxy, methyl, and cyclohexyl substituents on the antioxidant activities of indole derivatives. These indole derivatives were able to protect erythrocytes and DNA in a concentration‐dependent manner. The alkyl‐substituted indole can protect erythrocytes and DNA against AAPH‐induced oxidation. Especially, the structural features of cyclohexyl and methoxy substituents made MTC the best antioxidant among the indole derivatives used herein. Finally, the interaction between these indole derivatives and 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonate) radical cation and 2,2′‐diphenyl‐1‐picrylhydrazyl, respectively, provided direct evidence for these indole derivatives to scavenge radicals and emphasized the importance of electron‐donating groups for the free radical–scavenging activity of indole derivatives. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:273–279, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20289     

In Vitro Antioxidative Activity of (−)-Epicatechin Glucuronide Metabolites Present in Human and Rat Plasma

Recently we identified four conjugated glucuronide metabolites of epicatechin, (?)-epicatechin-3′-O-glucuronide (E3′G), 4′-O-methyl-(?)-epicatechin-3′-O-glucuronide (4′ME3′G), (?)-epicatechin-7-O-glucuronide (E7G) and 3′-O-methyl-(?)-epicatechin-7-O-glucuronide (3′ME7G) from plasma and urine. E3′G and 4′ME3′G were isolated from human urine, while E7G and 3′ME7G were isolated from rats that had received oral administration of (?)-epicatechin (Natsume et al. (2003), Free Radic. Biol. Med. 34, 840–849). It has been suggested that these metabolites possess considerable in vivo activity, and therefore we carried out a study to compare the antioxidant activities of the metabolites with that of the parent compound. This was achieved by measuring superoxide scavenging activity, reduction of plasma TBARS production and reduced susceptibility of low-density-lipoprotein (LDL) to oxidation. (?)-Epicatechin was found to have more potent antioxidant activity than the conjugated glucuronide metabolites. Both (?)-epicatechin and E7G had marked antioxidative properties with respect to superoxide radical scavenging activity, plasma oxidation induced by 2,2′-azobis-(2-aminopropane) dihydrochloride (AAPH) and LDL oxidation induced by copper ions or 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN). In contrast, the other metabolites had light antioxidative activities over the range of physiological concentrations found in plasma.     

Kinetic Study of the Inhibition of Linoleic Acid Oxidation in Aqueous Media by Phenolic Compounds

The antioxidant activity of several phenolic compounds has been evaluated in terms of the inhibition of the lipid oxidation. The extent of linoleic acid oxidation was monitored by the absorption of the conjugated diene hydroperoxydes formed as a result of oxidation. The antioxidant activity of phenolic compounds was evaluated in aqueous media consisting of negatively-charged micelles of sodium dodecyl sulfate (SDS) or positively-charged micelles of hexadecyl trimethylammonium bromide (HDTBr). 2,2′-azobis-(2-amidinopropane)-dihydrochloride (ABAP) was employed as the oxidation initiator. The assayed phenolic compounds showed good antioxidant efficiency, closely related to the presence of hydroxyl groups and the electron delocalization within the structure, which may stabilize the formed phenoxyl radicals. The kinetic analysis revealed that the oxidizability of linoleic acid was 10-fold higher in SDS than in HDTBr media, which could indicate that oxidation is favoured in negatively charged SDS micelles regarding to positive HDTBr medium. Furthermore, a greater antioxidant efficiency of phenolic compounds was found in HDTBr than in SDS micelles.     

Development of a defined medium for Clostridium scatologenes ATCC 25775

Aims:  To develop a defined medium for Clostridium scatologenes ATCC 25775, which produces the malodorants 3-methylindole (skatole) and 4-methylphenol ( p- cresol).
Methods and Results:  Clostridium scatologenes was cultured in anaerobic broth medium (pH 6·3) at 37°C containing ammonia, minerals and a commercial vitamin solution. Data indicate α-ketoglutarate, l- glutamate or l- glutamine is a required nutrient that can also serve as a primary carbon and energy source. When cultured in defined medium containing glutamate; glucose, fructose and betaine served as primary carbon and energy sources. l- Tryptophan, l- tyrosine, sorbitol and indole acetic acid did not enhance growth. In the absence of tryptophan, cells produced indole when grown using glucose or fructose. 4-Methylphenol was produced when growing cells were supplied with tyrosine. When supplied with tryptophan, 3-methylindole was produced by glucose- or fructose-growing cells but not from glutamate-growing cells. Cells grown in the presence of pyruvate produced indole, 3-methylindole and 4-methylphenol.
Conclusions:  Clostridium scatologenes requires α-ketoglutarate, l- glutamate, or l- glutamine for growth in defined medium. Cells produce indole when glucose or fructose is included in defined medium.
Significance and Impact of the Study:  The development of a defined medium will assist in physiology studies and genetic analysis of this strain.     

Evaluation of the antioxidant properties of thyroid hormones and propylthiouracil in the brain-homogenate autoxidation system and in the free radical-mediated oxidation of erythrocyte membranes

The antioxidant capacity of thyroid hormones and the antithyroid drug propylthiouracil was studied in three model systems, namely, autoxidation of rat brain homogenates and oxidation of rat erythrocyte plasma membranes (EPM) induced by either 2,2'-azobis-(2-amidinopropane) (AAP) thermolysis or by gamma irradiation. Thyroid hormones significantly inhibited the development of lipid peroxidation in these systems at micromolar concentrations, as assessed either by visible light emission, thiobarbituric acid reactive substances accumulation or oxygen uptake. This behaviour was not observed when L-3,3',5-triiodothyronine (T3) and L-thyroxine (T4) were assayed at nanomolar concentrations. In EPM exposed to AAP or gamma irradiation, propylthiouracil inhibited the induced lipid peroxidation, with Q1/2 values of 112-150 microM. It is concluded that the antioxidant capacity of thyroid hormones found in vitro may not be of relevance in physiological conditions, which exhibit variations of T3 and T4 levels in the nanomolar range. On the other hand, the behaviour of propylthiouracil as an inhibitor of EPM lipid peroxidation is observed at concentrations close to the therapeutic levels, thus representing a possible complementary action to its antithyroid activity.     

The inhibition of lipid autoxidation by human caeruloplasmin.

1. Purified caeruloplasmin was shown to inhibit lipid autoxidation induced by ascorbic acid or inorganic iron in the following systems: (a) an emulsion of linolenic acid in water; (b) an untreated ox brain homogenate in phosphate buffer; (c) a similar homogenate whose susceptibility to autoxidation had been abolished by dialysis or by heating and then restored by the above pro-oxidants. 2. The optimum conditions for this antioxidant activity were studied. 3. Caeruloplasmin did not inhibit autoxidation by u.v. irradiation in dialysed or preheated homogenates. 4. The apoprotein (without copper) had no antioxidant activity, whereas CuSO4 alone was much less effective as an antioxidant. 5. Iron-free transferrin also had some antioxidant activity.     

Comparison of antioxidant effectiveness of lipoic acid and dihydrolipoic acid

The abilities of dihydrolipoic acid (DHLA) to scavenge peroxynitrite (ONOO^?), galvinoxyl radical, 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonate) cation radical (ABTS^+?), and 2,2′‐diphenyl‐1‐picrylhydrazyl radical (DPPH) were higher than those of lipoic acid (LA). The effectiveness of DHLA to protect methyl linoleate against 2,2′‐azobis(2‐amidinopropane hydrochloride) (AAPH)‐induced oxidation was about 2.2‐fold higher than that of LA, and DHLA can retard the autoxidation of linoleic acid (LH) in the β‐carotene‐bleaching test. DHLA can also trap ～0.6 radicals in AAPH‐induced oxidation of LH. Moreover, DHLA can scavenge ～2.0 radicals in AAPH‐induced oxidation of DNA and AAPH‐induced hemolysis of erythrocytes, whereas LA can scavenge ～1.5 radicals at the same experimental conditions. DHLA can protect erythrocytes against hemin‐induced hemolysis, but accelerate the degradation of DNA in the presence of Cu²⁺. Therefore, the antioxidant capacity of –SH in DHLA is higher than S‐S in LA. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:216–223, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20378     

Calcium translocation by fatty acid derivatives in a two-phase partition model. Structure-activity relationships

The relationship between structures of fatty acid derivatives, long-chain fatty alcohols, phospholipids and their calcium-transporting activity was investigated using the two-phase model system in which ⁴⁵Ca is transported from an aqueous to an immiscible organic phase. Calcium translocation by all saturated and unsaturated fatty acids was significant only at 10 mM concentrations, but minimal or negligible below 1 mM; the corresponding methyl esters and alcohols were inactive at 10 mM. Polyunsaturated fatty acid derivatives, prepared by incubation with lipoxygenase (linoleate: oxygen oxidoreductase; EC 1.13.11.12) or by autoxidation in air, showed a markedly increased potency over the parent compounds. The oxidation products of linoleic and arachidonic acids were most potent. For example, the equieffective concentrations were 10 mM for linoleic acid, 0.4 mM for its lipoxygenase metabolites and 0.094 mM for its autoxidation products. Similarly, for arachidonic acid and its derivatives, equieffective concentrations were 10, 0.104 and 0.112 mM, respectively. The potency of the autoxidized fatty acid derivatives varied with both duration of autoxidation and the specific structure. Methyloleate and oleyl alcohol remained inactive even after a prolonged oxidation, whereas methyllinoleate and linoleyl alcohol were very potent only after 4 weeks but not after 1 week autoxidation. The potency of esters and alcohols with three or more double bonds increased significantly even after a short-term autoxidation, reflecting the differences in both the rate of formation and the contribution to calcium-transporting properties of the primary and secondary oxidation products. All phospholipids tested, with the exception of phosphatidylcholine and lysophosphatidylcholine, showed considerable calcium-transporting activities at 0.01 mM or greater concentrations; some members were of similar or greater potencies than the classical calcium ionophores, X537A and A23187.     

Iron autoxidation and free radical generation: effects of buffers, ligands, and chelators.

The pH of the solution along with chelation and consequently coordination of iron regulate its reactivity. In this study we confirmed that, in general, the rate of Fe(II) autoxidation increases as the pH of the solution is increased, but chelators that provide oxygen ligands for the iron can override the affect of pH. Additionally, the stoichiometry of the Fe(II) autoxidation reaction varied from 2:1 to 4:1, dependent upon the rate of Fe(II) autoxidation, which is dependent upon the chelator. No partially reduced oxygen species were detected during the autoxidation of Fe(II) by ESR using DMPO as the spin trap. However, upon the addition of ethanol to the assay, the DMPO:hydroxyethyl radical adduct was detected. Additionally, the hydroxylation of terephthalic acid by various iron-chelator complexes during the autoxidation of Fe(II) was assessed by fluorometric techniques. The oxidant formed during the autoxidation of EDTA:Fe(II) was shown to have different reactivity than the hydroxyl radical, suggesting that some type of hypervalent iron complex was formed. Ferrous iron was shown to be able to directly reduce some quinones without the reduction of oxygen. In conclusion, this study demonstrates the complexity of iron chemistry, especially the chelation of iron and its subsequent reactivity.     

Antioxidant properties of alpha-crystallin

-Crystallin is a major chaperone lens protein to which has been ascribed antioxidant functions. In the present work we have evaluated the antioxidant and free radical scavenging properties of bovine -crystallin in a series of in vitro models: zimosan-induced, luminol-enhanced chemiluminescence response of polymorphonuclear leukocytes, the autoxidation of brain homogenate, bleaching of 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)-derived radical cations, trapping of peroxyl radicals, and reactivity toward hypochloric acid. In all these systems, the reactivity of -crystallin is higher than or similar to that of bovine serum albumin. It is concluded that, given the high concentrations of -crystallin in the lenses, its capacity to interact with free radicals and to remove hypochlorous acid could contribute to the maintenance of the lens functionality.     

Autoxidation of naphthohydroquinones: Effects of pH,naphthoquinones and superoxide dismutase

The rates of autoxidation of a number of pure naphthohydroquinones have been determined, and the effects of pH, superoxide dismutase (SOD) and of the parent naphthoquinone on the oxidation rates have been investigated. Most compounds were slowly oxidised in acid solution with the rates increasing with increasing pH, although 2-hydroxy-, 2-hydroxy-3-methyl- and 2-amino-1,4-naphthohydroquinone were rapidly oxidised at pH 5 and the rates of oxidation of these substances were comparatively unresponsive to changes in pH. At pH 7.4, autoxidation rates decreased in the order 2,3-dichloro-1,4-naphthohydroquinone > 5-hydroxy > 2-bromo > 2-hydroxy-3-methyl > 2-amino > 2-hydroxy > 2-methoxy > 2,3-dimethoxy > 2,3-dimethyl > 2-methyl > unsubstituted hydroquinone. The autoxidation rates of the alkyl, alkoxy, hydroxy and amino derivatives were decreased in the presence of SOD, but this enzyme had no effect on the rate of autoxidation of the 2,3-dichloro and 2-bromo derivatives while that of the 5-hydroxy derivative was increased. The rates of autoxidation of all compounds except the halogen derivatives and 5-hydroxy-1,4-naphthohydroquinone were increased by addition of the parent naphthoquinone, and quinone addition partially or completely overcame the inhibitory effect of SOD. There is evidence that the reduction of quinones to hydroquinones in vivo may lead either to detoxification or to activation. This may be due to differences in the rate or mechanism of autoxidation of the hydroquinones that are formed, and the data gained in this study will provide a framework for testing this possibility.     

Antioxidant capacity of allopurinol in biological systems

The antioxidant capacity of allopurinol was investigated in three biological systems by measurements of visible chemiluminescence, oxygen uptake and production of thiobarbituric acid reactive substances (TBARS). The addition of allopurinol to rat brain homogenates undergoing autoxidation and erythrocyte ghost membranes supplemented with 2,2'-azo-bis-(2-amidinopropane), in concentrations up to 2 mM, has a negligible effect on lipid peroxidation development. In erythrocyte ghost membranes exposed to gamma irradiation (9.5 Gy/min), allopurinol inhibits the radiation-induced lipid peroxidation with a Q(1/2) of 2.0 mM. It is suggested that allopurinol may have an alternative antioxidant pathway of action in biological systems, probably through a scavenging action upon hydroxyl radicals.     

Design,synthesis, in vitro antiproliferative activity and apoptosis-inducing studies of 1-(3′,4′,5′-trimethoxyphenyl)-3-(2′-alkoxycarbonylindolyl)-2-propen-1-one derivatives obtained by a molecular hybridisation approach

Inhibition of microtubule function using tubulin targeting agents has received growing attention in the last several decades. The indole scaffold has been recognized as an important scaffold in the design of novel compounds acting as antimitotic agents. Indole-based chalcones, in which one of the aryl rings was replaced by an indole, have been explored in the last few years for their anticancer potential in different cancer cell lines. Eighteen novel (3′,4′,5′-trimethoxyphenyl)-indolyl-propenone derivatives with general structure 9 were synthesized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines. The highest IC₅₀ values were obtained against the human promyelocytic leukemia HL-60 cell line. This series of chalcone derivatives was characterized by the presence of a 2-alkoxycarbonyl indole ring as the second aryl system attached at the carbonyl of the 3-position of the 1-(3′,4′,5′-trimethoxyphenyl)-2-propen-1-one framework. The structure–activity relationship (SAR) of the indole-based chalcone derivatives was investigated by varying the position of the methoxy group, by the introduction of different substituents (hydrogen, methyl, ethyl or benzyl) at the N-1 position and by the activity differences between methoxycarbonyl and ethoxycarbonyl moieties at the 2-position of the indole nucleus. The antiproliferative activity data of the novel synthesized compounds revealed that generally N-substituted indole analogues exhibited considerably reduced potency as compared with their parent N-unsubstituted counterparts, demonstrating that the presence of a hydrogen on the indole nitrogen plays a decisive role in increasing antiproliferative activity. The results also revealed that the position of the methoxy group on the indole ring is a critical determinant of biological activity. Among the synthesized derivatives, compound 9e, containing the 2-methoxycarbonyl-6-methoxy-N-1H-indole moiety exhibited the highest antiproliferative activity, with IC₅₀ values of 0.37, 0.16 and 0.17?μM against HeLa, HT29 and MCF-7 cancer cell lines, respectively, and with considerably lower activity against HL-60 cells (IC₅₀: 18?μM). This derivative also displayed cytotoxic properties (IC₅₀ values ～1?μM) in the human myeloid leukemia U-937 cell line overexpressing human Bcl-2 (U-937/Bcl-2) via cell cycle progression arrest at the G₂-M phase and induction of apoptosis. The results obtained also demonstrated that the antiproliferative activity of this molecule is related to inhibition of tubulin polymerisation. The presence of a methoxy group at the C5- or C6-position of the indole nucleus, as well as the absence of substituents at the N-1-indole position, contributed to the optimal activity of the indole-propenone-3′,4′,5′-trimethoxyphenyl scaffold.     

An examination of the oxidation of mercury vapor by rat brain homogenate

The oxidation of mercury vapor (Hg degrees) to divalent inorganic mercury (Hg2+) was studied in rat brain homogenates. By using a "degassing" method, it was possible to speciate the mercury present in the homogenate and, for the first time, to measure the rate of oxidation as a function of the substrate (Hg degrees) concentration. Mercury oxidation was first-order with respect to substrate concentration at all concentrations tested, and the first-order rate constant for the oxidation process was proportional to homogenate concentration. The role of catalase compound I in mercury vapor oxidation by brain homogenate was examined by observing the effects of two inhibitors of catalase (catalase compound I) on homogenate mercury-oxidizing activity and catalase activity. Sodium azide (50 mM) completely inhibited both mercury-oxidizing activity and catalase activity. Aminotriazole (3-amino-1H-1,2,4-triazole) (50 mM) completely inhibited only mercury-oxidizing activity; some residual catalase activity was found in the aminotriazole-treated homogenate. It was concluded that catalase compound I plays a major role in the oxidation of Hg degrees, but the possibility that catalase-independent pathways make a minor contribution cannot be excluded.     

Kinetics of the lipoperoxyl radical-scavenging activity of indicaxanthin in solution and unilamellar liposomes

The reaction of the phytochemical indicaxanthin with lipoperoxyl radicals generated in methyl linoleate methanol solution by 2,2′-azobis(2,4-dimethylvaleronitrile), and in aqueous soybean phosphatidylcholine unilamellar liposomes by 2,2′-azobis(2-amidinopropane)hydrochloride, was studied. The molecule acts as a chain-terminating lipoperoxyl radical scavenger in solution, with a calculated inhibition constant of 3.63 × 10⁵ M^{? 1} s^{? 1}, and a stoichiometric factor approaching 2. Indicaxanthin incorporated in liposomes prevented lipid oxidation, inducing clear-cut lag periods and decrease of the propagation rate. Both effects were concentration-dependent, but not linearly related to the phytochemical concentration. The consumption of indicaxanthin during liposome oxidation was remarkably delayed, the lower the concentration the longer the time-interval during which it remained in its native state. Indicaxanthin and α-tocopherol, simultaneously incorporated in liposomes, exhibited cooperative antioxidant effects and reciprocal protective interactions. The extent of synergism decreased at the increase of the ratio (indicaxanthin)/(α-tocopherol). A potential antioxidant mechanism of indicaxanthin is discussed in the context of the chemistry of the molecule, and of the possible reactivity of a short-lived intermediate.     

Scavenging of reactive oxygen species by N‐substituted indole‐2 and 3‐carboxamides

Indole‐2 and 3‐carboxamides (IDs) are proposed to be selective cyclooxygenase inhibitors. Since cyclooxygenase‐1 may be involved in reactive oxygen species (ROS) production, we hypothesize that these indole derivatives have antioxidative properties. We have employed chemiluminescence (CL) and electron spin resonance (ESR) spin trapping to examine this hypothesis. We report here the results of a study of reactivity of 10 selected indole derivatives towards ROS. The following generators of ROS were applied: potassium superoxide (KO₂) as a source of superoxide radicals (O₂^·?), the Fenton reaction (Co‐EDTA/H₂O₂) for hydroxyl radicals (HO^·), and a mixture of alkaline aqueous H₂O₂ and acetonitrile for singlet oxygen (¹O₂). Hydroxyl radicals were detected as 5,5‐dimethyl‐1‐pyrroline‐N‐oxide (DMPO) spin adduct, whereas 2,2,6,6‐tetramethyl‐piperidine (TEMP) was used as a detector of ¹O₂. Using the Fenton reaction, 0.5 mmol/L IDs were found to inhibit DMPO‐?H radical formation in the range 7–37%. Furthermore the tested compounds containing the thiazolyl group also inhibited the ¹O₂‐dependent TEMPO radical, generated in the acetonitrile + H₂O₂ system. About 20% inhibition was obtained in the presence of 0.5 mmol/L IDs. 1 mmol/L IDs caused an approximately 13–70% decrease in the CL sum from the O₂^·? generating system (1 mmol/L). The aim of this paper is to evaluate these indole derivatives as antioxidants and their abilities to scavenge ROS. Copyright © 2004 John Wiley & Sons, Ltd.     

Binding geometries of triple helix selective benzopyrido [4,3-b]indole ligands complexed with double- and triple-helical polynucleotides

The binding modes of three benzopyrido [4,3-b]indole derivatives (and one benzo[-f]pyrido [4-3b] quinoxaline derivative) with respect to double helical poly(dA) · poly(dT) and poly[d(A-T)]₂ and triple-helical poly(dA) · 2poly(dT) have been investigated using linear dichroism (LD) and CD: (I) 3-methoxy-11-amino-BePI where BePI = (7H-8-methyl-benzo[e]pyrido [4,3-b]indole), (II) 3-methoxy-11-[(3′-amino) propylamino]-BePI, (III) 3-methoxy-7-[(3′-diethylamino)propylamino] BgPI where BgPI = (benzo[g]pyrido[4,3-b]indole), and (IV) 3-methoxy-11-[(3′-amino)propylamino] B f P Q where B f P Q = {benzo[-f]pyrido[4-3b]quinoxaline}. The magnitudes of the reduced LD of the electronic transitions of the polynucleotide bases and of the bound ligands are generally very similar, suggesting an orientation of the plane of the ligands' fused-ring systems preferentially perpendicular to the helix axis. The LD results suggest that all of the ligands are intercalated for all three polynucleotides. The induced CD spectrum of the BePI chromophore in the (II-BePI)-poly[d(A-T)]₂ complex is almost a mirror image of that for the (I-BePI)-poly(dA) · poly(dT) and (I-BePI)-poly(dA) · 2poly(dT) complexes, suggesting an antisymmetric orientation of the BePI moiety upon intercalation in poly[d(A-T)]₂ compared to the other polynucleotides. The induced CD of I-BePI bound to poly(dA) · 2poly(dT) suggests a geometry that is intermediate between that of its other two complexes. The concluded intercalative binding as well as the conformational variations between the different BePI complexes are of interest in relation to the fact that BePI derivatives are triplex stabilizers. © 1997 John Wiley & Sons, Inc. Biopoly 42: 101–111, 1997     

2,2′-dithienyl diselenide,an organoselenium compound,elicits antioxidant action and inhibits monoamine oxidase activity in vitro

Context: Organoselenium compounds have been described as antioxidant and neuroprotective agents.

Objective: To evaluate the antioxidant action of 2,2′-dithienyl diselenide (DTDS) and its effects in brain monoamine oxidase (MAO) activity in vitro.

Materials and methods: Assays for reactive species (RS), lipid peroxidation, protein oxidation, MAO A and B activities in rat brain homogenate as well as mimetic dehydroascorbate reductase and glutathione S-transferase activities were performed using DTDS (μM range).

Results: DTDS was effective in decreasing the levels of RS as well as lipid peroxidation induced by malonate, sodium nitroprusside or FeCl₂/EDTA and protein carbonyl in the rat brain homogenate. DTDS elicited dehydroascorbate reductase-like and glutathione S-transferase-like activities. DTDS was effective in inhibiting both MAO-A and MAO-B activities.

Discussion: The results demonstrated that DTDS is an antioxidant agent with non-selective inhibitory effect on MAO activity.

Conclusion: DTDS is a promising molecule to be evaluated in experimental models of neurological diseases.     

2,2′-Dipyridyl diselenide is a better antioxidant than other disubstituted diaryl diselenides

The aim of this study was to investigate the in vitro antioxidant activity of 2,2'-dipyridyl diselenide (e) by comparing this effect with m-trifluoromethyl-diphenyl diselenide (a), p-fluor-diphenyl diselenide (b), p-chloro-diphenyl diselenide (c), and p-methoxyl-diphenyl diselenide (d) in rat liver homogenate. We also investigated if the mechanisms involved in the antioxidant property of 2,2'-dipyridyl diselenide are the same that of other diselenides. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC) levels were determined in rat liver homogenate, as indicators of antioxidant activity. Dehydroascorbate (DHA) reductase- and glutathione S-transferase (GST)-like activities, 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical-scavenging activities and the protection against the oxidation of Fe(2+) were determined to better understand the antioxidant property of compounds. δ-Aminolevulinic dehydratase (δ-ALA-D) activity was also carried out in rat liver homogenates, as a toxicological parameter. Compound e showed the highest potency in reducing TBARS (order of IC(50) values: e < b ≤ a < d ≤ c) and PC (order of IC(50) values: e < c ≤ b ≤ a < d) levels and lower potency in inhibiting δ-ALA-D activity than other diselenides. Compound e at all concentrations tested had no enzyme-mimetic property, but had radical-scavenging activity (≥5 μM) and protected against the oxidation of Fe(2+) (50 μM); while compounds a-d showed GST and DHA-mimetic activities and protected against the oxidation of Fe(2+), but had not radical-scavenging activities. This study indicates that (i) 2,2'-dipyridyl diselenide (e) had better in vitro antioxidant effect than other diselenides and lower inhibitory effect on δ-ALA-D activity, (ii) the presence of pyridine ring is responsible for the best antioxidant effect of this compound, and (iii) 2,2'-dipyridyl diselenide acts by different mechanisms of other diselenides.     

Inhibition of Lipid Peroxidation by N-Acetylserotonin and Its Role in Retinal Physiology

N-Acetylserotonin (NAS) inhibits the peroxidation of linoleic acid induced by a water-soluble initiator, 2,2′-azobis(2-amidinopropane) (ABAP). Lipid peroxidation was detected by the formation of conjugated dienes, monitored spectrophotometrically at 236 nm. N-Acetylserotonin, at concentrations ranging from 200 nM to 20 μM, reduced the rate of ABAP-initiated lipid peroxidation in a concentration-dependent manner. The results of NAS-inhibited lipid peroxidation are compared to the antioxidant activities of melatonin, vitamin E, and a water-soluble vitamin E analog, Trolox. It is suggested that NAS acts as a physiological antioxidant in retinal photoreceptor cells.