Δ-aminolevulinic Dehydratase Research Articles

3-Alkynyl selenophene protects against carbon-tetrachloride-induced and 2-nitropropane-induced hepatic damage in rats

The aim of this study was to investigate the protective effect of 3-alkynyl selenophene (3-ASP) on acute liver injury induced by carbon tetrachloride (CCl(4)) and 2-nitropropane (2-NP) in rats. On the first day of treatment, the animals received 3-ASP (25mg/kg, p.o.). On the second day, the rats received CCl(4) (1mg/kg, i.p.) or 2-NP (100mg/kg, p.o.). Twenty-four hours after CCl(4) or 2-NP administration, the animals were euthanized, and their plasma and liver were removed for biochemical and histological analyses. The histological analysis revealed extensive injury in the liver of CCl(4)-exposed and 2-NP-exposed rats, which was attenuated by 3-ASP. 3-ASP significantly attenuated (1) the increase in plasmatic aspartate and alanine aminotransferase activities and lipid peroxidation levels induced by CCl(4) and 2-NP; (2) the inhibition of δ-aminolevulinic dehydratase activity caused by 2-NP; and (3) the decrease in ascorbic acid (AA) levels and catalase (CAT) activity caused by CCl(4). AA levels and CAT activity remained unaltered in the liver of rats exposed to 2-NP. The protective effect of 3-ASP on acute liver injury induced by CCl(4) and 2-NP in rats was demonstrated.

Inhibition of δ-aminolevulinate dehydratase is not closely related to the development of hyperglycemia in alloxan-induced diabetic mice

Alloxan is a compound widely used in models of diabetes mellitus due to its ability for damage insulin-producing β-cells. The aim of this study was to investigate acute (after 24 h) and sub-acute (after seven days) effects of 200 mg/kg alloxan administration on mice. Biochemical parameters as liver, kidney, and blood δ-ALA-D activity, total sulfhydryl content of hepatic and renal tissues, and hepatic and renal content of malondialdehyde (MDA) were evaluated. The histopathology of hepatic and renal tissues of alloxan-treated and control animals was carried out. Further, blood glucose levels were determined in an attempt to correlate alloxan-induced hyperglycemia with changes in thiol status. Results showed that mice exhibited a significant inhibition of hepatic and renal δ-ALA-D activity in addition to a significant decrease in total sulfhydryl groups of same tissues in both acute and sub-acute alloxan administrations. Moreover, alloxan-induced inhibition of δ-ALA-D activity was partly suppressed when enzymatic assay was performed in the presence of dithiothreitol, suggesting that inhibitory effect of alloxan on δ-ALA-D activity is, at least partially, related to the oxidation of the enzyme’s essential thiol groups. Blood δ-ALA-D activity was significantly inhibited only 24 h after alloxan administration; however, at this time, a hyperglycemic status was not observed in animals. In contrast, a significant increase in blood glucose levels was observed seven days after alloxan administration. Despite of alterations in biochemical parameters, histological tissue examination of alloxan-treated mice revealed typical renal and hepatic parenchyma. Therefore, these results showed that acute toxic effects of alloxan are related, at least partially, to depletion of sulfhydryl groups, and do not closely relate to the development of hyperglycemia in mice.

Synthesis of 5′-seleno-xylofuranosides

The synthesis of selenium derivatives of naturally occurring chiral molecules is becoming increasingly important in recent years. In this context, we describe herein an easy, straightforward synthetic route for the preparation of a series of chiral seleno-furanosides, starting from the readily available carbohydrate d-xylose. In addition, selected compounds were screened as inhibitors of the δ-aminolevulinate dehydratase (δ-ALA-D) enzyme. Diselenide 4 was found to reduce significantly the enzymatic activity, while seleno-furanoside 1a increased δ-ALA-D activity.

Protective effect of crude extract from Wedelia paludosa (Asteraceae) on the hepatotoxicity induced by paracetamol in mice

Several in-vitro and in-vivo ethnopharmacological studies carried out with plants of the genus Wedelia have already demonstrated hepatoprotective effects in chemically-induced liver injury, including those induced by paracetamol. Here, the effects of the crude extract from Wedelia paludosa on paracetamol-induced hepatotoxicity in mice was investigated. Intraperitoneal injection of paracetamol (1,000 mg kg(-1)) caused 80% death after 24 h in mice, which was significantly reduced by oral pretreatment with W. paludosa (500 mg kg(-1)). Hepatotoxicity was observed 24 h after an intraperitoneal injection of paracetamol (600 mg kg(-1)), as evidenced by an increase in plasma activity of aspartate and alanine aminotransferases. That hepatotoxicity was significantly attenuated by W. paludosa pretreatment (100-500 mg kg(-1)) in a dose-response manner. Paracetamol (1,000 mg kg(-1)) drastically depleted total glutathione levels and decreased glutathione peroxidase and delta-aminolevulinate dehydratase activity in the liver, such effects not being prevented by pretreatment with W. paludosa. Neither paracetamol treatment alone nor pretreatment with W. paludosa altered glutathione reductase and glutathione S-transferase activity or the levels of end-products of lipid peroxidation. In conclusion, we found that W. paludosa protected against paracetamol-induced hepatotoxicity, an effect not observed over oxidative stress-related parameters. Hepatoprotection is likely mediated by some terpenes present in W. paludosa extract. However, further studies will be required to explain the mechanisms involved in the hepatoprotection afforded by W. paludosa.

Lipoic acid blocks seizures induced by pilocarpine via increases in δ-aminolevulinic dehydratase and Na +, K +-ATPase activity in rat brain

In the present study we investigated the effects of lipoic acid (LA) on δ-aminolevulinic dehydratase (δ-ALA-D) and Na +, K +-ATPase activities in rat brain after seizures induction by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (10 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), or the combination of LA (10 mg/kg, i.p.) with pilocarpine (400 mg/kg, i.p.), 30 min before administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 1 h. The enzyme activities (δ-ALA-D and Na +, K +-ATPase) were measured using spectrophotometric methods, and the results were compared with that obtained from saline and pilocarpine-treated animals. Neuroprotective effects of LA against seizures were evaluated based on those enzyme activities. The pilocarpine group showed a reduction in δ-ALA-D and Na +, K +-ATPase activities after seizures. In turn, LA plus pilocarpine abolished the appearance of seizures and reversed the decreased in δ-ALA-D and Na +, K +-ATPase activities produced by seizures, when compared to the pilocarpine seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing δ-ALA-D and Na +, K +-ATPase activities in rat brain during seizures.

Influence of cereal bran supplement on cadmium effects in growing rats

Strategies to diminish cadmium (Cd) absorption are highly desirable especially where Cd exposure due to environmental contamination is still inevitable. Cd toxicity may be influenced by dietary components, such as fiber and minerals. Multimixtures are low-cost cereal bran supplements used in Brazil and in other countries to counteract malnutrition in low-income populations. This study was aimed at evaluating whether multimixture would reduce Cd effects in young rats. Animals received a diet with or without the multimixture plus 0, 5, or 25 mg Cd/kg (control, Cd-5, and Cd-25 groups) during 30 days. The Cd-5 groups were similar to control groups in all parameters analyzed, except in the higher renal Cd concentration. However, the Cd-25 groups had lower biological growth parameters and renal delta-aminolevulinate dehydratase activity, besides higher renal Cd concentration and plasma alanine aminotransferase activity compared to the controls. The multimixture did not prevent Cd effects in the Cd-25 group, but caused a small reduction in renal Cd concentration in the Cd-5 group. Although this multimixture was ineffective to prevent Cd effects at the higher concentration, it seemed to reduce Cd accumulation at the lower Cd dietary concentration, which is similar to levels of human exposure in some polluted areas.

Mercury exposure and oxidative stress in communities of the Brazilian Amazon

This study was designed to assess possible associations between biomarkers of mercury (Hg) exposure and oxidative stress in fish-eating Amazonian communities. Clinical samples were obtained from riparians living in the Brazilian Amazon. Biomarkers of oxidative stress (glutathione – GSH, glutathione peroxidase - GSH-Px, catalase - CAT, activity and reactivation index of δ-aminolevulinate dehydratase - ALA-D (R%) were determined in blood. Total Hg was measured in whole blood (B-Hg), plasma (P-Hg) and hair (H-Hg). Association between biomarkers of Hg exposure and oxidative stress were examined using multiple regression models, including age, gender, alcohol consumption, smoking status, fish consumption and then stratified for gender. Significant inverse relations were observed between GSH-Px, GSH, CAT, ALA-D activity and B-Hg or H-Hg (p < 0.05). ALA-D reactivation index was positively related to B-Hg (p < 0.0001). P-Hg was directly related to ALA-D reactivation index and inversely associated with GSH-Px, GSH, and ALA-D activity (p < 0.05). When stratified for gender, women showed significant inverse associations between all biomarkers of Hg exposure and CAT (p < 0.05) or GSH (p < 0.05), while for men only P-Hg showed a significant inverse relation with GSH (p < 0.001). Our results clearly demonstrated an association between Hg exposure and oxidative stress. Moreover, for B-Hg, P-Hg and H-Hg gender differences were present.

Involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide on testicular damage induced by cadmium in mice

The involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide (PhSe) 2 on testicular damage caused by cadmium in mice was investigated. Mice received a single dose of CdCl 2 (5 mg/kg, intraperitoneally). Thirty minutes after the CdCl 2 injection, they received a single oral dose of (PhSe) 2 (400 μmol/kg). Twenty-four hours after CdCl 2 administration, blood samples were collected and mice were killed and had their testes dissected. Parameters in plasma (aspartate (AST) and alanine (ALT) aminotransferases and lactato dehydrogenase (LDH) activities as well as creatinine levels) were determined. The activity of δ-aminolevulinate dehydratase (δ-ALA-D), the levels of thiobarbituric acid-reactive substances (TBARS), ascorbic acid and nonprotein thiols (NPSH) and histological analysis were determined in collected samples. Results demonstrated that (PhSe) 2 protected against toxicity induced by CdCl 2 on δ-ALA-D activity, ascorbic acid and NPSH levels. (PhSe) 2 protected against the increase in plasma AST, ALT and LDH activities caused by CdCl 2. Testes of mice exposed to CdCl 2 showed marked histopathological alterations that were ameliorated by administration of (PhSe) 2. (PhSe) 2 protected against toxicity induced by CdCl 2 in testes of mice. Ascorbic acid and NPSH, non-enzymatic antioxidant defenses, are involved in the protective effect of (PhSe) 2 against testicular damage caused by CdCl 2 in mice.

Passive smoke exposure induces oxidative damage in brains of rat pups: Protective role of diphenyl diselenide

The protective effect of diphenyl diselenide, (PhSe)2, on oxidative stress induced by cigarette smoke exposure in brains of rat pups was evaluated. Animals were exposed to passive cigarette smoke (15 min/day) in two different experimental protocols: P1 (1, 2, and 3 cigarettes) and P2 (4, 5, and 6 cigarettes) for 3 weeks. Before each period of smoke exposure, animals received an oral administration of (PhSe)2 (0.5 mg/kg). A number of toxicological parameters in the brain were examined, such as lipid peroxidation, δ-aminolevulinate dehydratase (δ-ALA-D) activity, and components of enzymatic (superoxide dismutase and catalase activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol levels). In P1, smoke exposure induced an inhibition of catalase activity and an increase of ascorbic acid levels. (PhSe)2 treatment was able to protect catalase activity but not ascorbic acid levels. In P2, an augmentation of lipid peroxidation, a reduction of enzymatic and non-enzymatic antioxidant status, and an inhibition of δ-ALA-D activity caused by smoke exposure were found. (PhSe)2 protected the brains of rat pups against oxidative damage induced by smoke exposure. The results are consistent with the antioxidant effect of (PhSe)2 demonstrated by the reduction of oxidative changes caused by smoke exposure in the brains of pups.

Chronic Treatment with Fluphenazine Alters Parameters of Oxidative Stress in Liver and Kidney of Rats

The aim of this study was to assess the toxic effects of chronic exposure to fluphenazine in liver and kidney of rats, as well as the possible protective effect of diphenyl diselenide on the fluphenazine-induced damage. Long-term treatment with fluphenazine caused an increase in lipid peroxidation levels in liver and kidney homogenates. Diphenyl diselenide treatment did not affect delta-aminolevulinate dehydratase (delta-ALA-D) activity, but fluphenazine alone or in combination with diphenyl diselenide showed an inhibitory effect on delta-ALA-D activity in liver. Diphenyl diselenide plus fluphenazine treatment increased the reactivation index of hepatic delta-ALA-D by approximately 80%. Superoxide dismutase activity decreased in liver of rats treated with fluphenazine alone. The combined treatment with fluphenazine and diphenyl diselenide was able to ameliorate superoxide dismutase activity in liver of rats. Catalase activity was augmented in liver from rats treated with fluphenazine, and this increase was prevented when diphenyl diselenide was co-administered. Taken together, these results indicate that the association of diphenyl diselenide with fluphenazine could protect the liver from lipid peroxidation and ameliorate superoxide dismutase and catalase activities. Moreover, our data point to the relationship between the oxidative stress and fluphenazine treatment in liver and kidney of rats.

Hepatoprotective effect of 3-alkynyl selenophene on acute liver injury induced by D-galactosamine and lipopolysaccharide

The aim of this study was to investigate the hepatoprotective effect of 3-alkynyl selenophene (compound a), a selenophene compound, on acute liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in rats. The animals received compound a (25 and 50 mg/kg; per oral, p.o.) in the first day of treatment. In the second day, the rats received D-GalN (500 mg/kg; intraperitoneal, i.p.) and LPS (50 μg/kg; intraperitoneal, i.p.). Twenty-four hours after D-GalN/LPS administration animals were euthanized to the biochemical and histological analysis. Compound a (25 and 50 mg/kg; p.o.) protected against the increase in aspartate aminotransferase (AST) activity induced by D-GalN/LPS. Compound a at 50 mg/kg protected against the increase in alanine aminotransferase (ALT) activity induced by D-GalN/LPS. The inhibition of δ-aminolevulinic dehydratase (δ-ALA-D) activity and the decrease of ascorbic acid levels caused by D-GalN/LPS were protected by compound a (25 and 50 mg/kg). Glutathione S-transferase (GST) and catalase activities were not altered in all groups. The histological data showed that sections of liver from D-GalN/LPS-treated rats presented massive hemorrhage, the presence of inflammatory cells and necrosis. Compound a attenuated D-GalN/LPS-induced hepatic histopathological alterations. Based on the results, we demonstrated the hepatoprotective effect of compound a on acute liver injury induced by D-GalN/LPS.

Protective effect of disubstituted diaryl diselenides on cerebral oxidative damage caused by sodium nitroprusside

Disubstituted diaryl diselenides, a class of organoselenium compounds, were investigated for antioxidant activity in rat brain homogenates. Diphenyl diselenide (PhSe)2, m-trifluoromethyl-diphenyl diselenide (m-CF3–C6H4Se)2, p-chloro-diphenyl diselenide (p-Cl–C6H4Se)2 and p-methoxyl-diphenyl diselenide (p-CH3O–C6H4Se)2 were tested against lipid peroxidation (LP) induced by sodium nitroprusside (SNP) or malonate and oxidatively modified proteins (OP) induced by SNP in vitro. Disubstituted diaryl diselenides protected against LP and OP. Disubstituted diaryl diselenides were investigated against oxidative damage caused by SNP in mouse brain. Mice were pre-treated with disubstituted diaryl diselenides (25mg/kg, oral route, p.o.) and subsequently received SNP (0.35μM/site i.c.v.). The levels of LP and OP, and activities of catalase, δ-aminolevulinate dehydratase (δ-ALA-D) and Na+, K+-ATPase were evaluated in vivo. All disubstituted diaryl diselenides protected against the increase of LP and OP induced by SNP, while only (PhSe)2 and (m-CF3–C6H4Se)2 were able to protect against δ-ALA-D and Na+, K+-ATPase inhibition induced by SNP. In conclusion, (p-Cl–C6H4Se)2 and (m-CF3–C6H4Se)2 were most efficient against lipid and protein oxidation in rat brain homogenates in vitro. All disubstituted diaryl diselenides protected against oxidative damage caused by the administration of SNP in mice in vivo.

Studies on preventive effects of diphenyl diselenide on acetaminophen-induced hepatotoxicity in rats

Organoselenium are compounds with important antioxidant activity and with many biological activities interesting from pharmacological point of view. The aim of this study was to evaluate the protective effect of diphenyl diselenide (PhSe) 2 on hepatotoxicity caused by administration of acetaminophen (AA) in rats. Rats received (PhSe) 2 orally (31 mg/kg, dissolved in canola oil) for 2 days. After the second day of treatment, rats received AA orally (2 g/kg) in unique dose. Twenty-four hours after the last administration of AA, plasma was used for biochemical assays aspartate (AST) and alanine aminotransferases (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), γ-glutamyl transferase (γ-GT) activities. Glutathione- S-transferase (GST), δ-aminolevulinic dehydratase (δ-ALA-D) and catalase activities as well as ascorbic acid and TBARS levels were determined in the liver of rats. (PhSe) 2 protected against the increase in AST, ALT, ALP, LDH and γ-GT activities induced by AA exposure to rats. The histological data showed that sections of liver from AA-exposed rats presented intense cellular necrosis, characterized by the presence of Kupffer cells and other infiltrating cells, mainly around of the centrilobular vein. (PhSe) 2 significantly attenuated AA-induced hepatic histopathological alterations. Administration of (PhSe) 2 protected against the increase in TBARS levels and the decrease in δ-ALA-D and GST activities as well as ascorbic acid content induced by AA exposure in rats. Catalase activity remained unaltered in all treated groups. The protective effect of (PhSe) 2 against hepatotoxicity caused by AA exposure in rats was demonstrated.

Antioxidant effect of a novel class of telluroacetilene compounds: Studies in vitro and in vivo

Aims The effect of telluroacetylenes a–d on pharmacological assays was investigated in vitro. A second objective of this study was to investigate the antioxidant action of compound b against the oxidative damage induced by sodium nitroprusside (SNP) in mouse brain. Main methods In in vitro experiments, lipid peroxidation (LP) and protein carbonyl (PC) levels and δ-aminolevulinate dehydratase (δ-ALA-D) activity were carried out in rat brain homogenate. The thiol peroxidase-like activity and DPPH radical scavenging of telluroacetylenes a–d were investigated. In in vivo experiments, mice received SNP (0.335 µmol per site) intra cerebroventricular (i.c.v.) thirty minutes after oral administration of telluroacetylene b (10 mg/kg). After 1 h, animals were euthanized. The levels of LP and δ-ALA-D, catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities were carried out in mouse brain homogenate. Key findings Telluroacetylenes a–d, at low μM range, reduced LP and PC levels in rat brain homogenate. Telluroacetylenes a–d showed effect of scavenging DPPH radicals. δ-ALA-D activity was inhibited by telloruacetylenes a–d, at high μM range, in rat brain homogenate. Brains of mice treated with SNP showed an increase in LP and the reduction in δ-ALA-D, GR and GST activities. Telluroacetylene b protected against the oxidative stress caused by SNP in brain of rats. Significance The results support an antioxidant effect of telluroacetylenes a–d in vitro. Telluroacetylene b protected against oxidative damage caused by SNP in mouse brain, suggesting an antioxidant effect of this compound.

δ-Aminolevulinate dehydratase activity and oxidative stress during melphalan and cyclophosphamide–BCNU–etoposide (CBV) conditioning regimens in autologous bone marrow transplantation patients

Severe toxicity is associated with cytotoxic drugs used during the conditioning regimen (CR) preceding bone marrow transplantation (BMT). The aim of this study was to evaluate the involvement of oxidative stress and possible use of δ-aminolevulinate dehydratase (δ-ALA-D) activity as a marker of oxidative stress in autologous BMT patients. We have also compared common drugs that are used during CR, namely, melphalan (M-200) and cyclophosphamide–BCNU–etoposide (CBV), in order to determine whether either of them could be less toxic to patients in terms of oxidative stress. The sample consisted of 10 patients admitted for autologous BMT, 5 with M-200 CR and 5 with CBV CR and 10 healthy controls. Lipid peroxidation (estimated as thiobarbituric acid-reactive substances, TBARS), vitamin C, thiol levels, catalase, superoxide dismutase and δ-ALA-D activity were determined before CR, during CR and on days 10 and 20 after BMT. Signs of exacerbated oxidative stress were minimal before CR, except for the CVB group (patients with lymphoma) where an increase in TBARS and a decrease in P-SH were detected. Indices of oxidative stress changed in both groups (CBV and M-200) during CR and up to 20 days after BMT. There was a decrease in enzymatic and non-enzymatic antioxidant defenses and in δ-ALA-D activity and an increase in lipoperoxidation in the blood of both patient groups. In conclusion, CBV and, principally, M-200 caused oxidative stress in patients undergoing autologous BMT and blood δ-ALA-D activity seems to be an additional biomarker of oxidative stress in BMT patients.

If there is an effect of lead exposure on malaria, then the activity of δ-aminolevulinate dehydratase (ALAD) may play a role, as ALAD is imported by the parasite from the host

If there is an effect of lead exposure on malaria, then the activity of delta-aminolevulinate dehydratase (ALAD) may play a role, as ALAD is imported by the parasite from the host

Structural modifications into diphenyl diselenide molecule do not cause toxicity in mice

The aim of the present study was to evaluate toxicological parameters of following compounds: 1a (4,4′-dichloro-diphenyl diselenide [(ClPhSe) 2]), 1b (3,3′-ditrifluoromethyl-diphenyl diselenide [(F 3CPhSe) 2]) and 1c (4,4′-dimethoxyl-diphenyl diselenide [(CH 3OPhSe) 2]). Calculated lethal dose (LD 50) values for mice exposed, by oral route, to a single application of compounds 1a, 1b or 1c were estimated to be >381, 278 and >372 mg/kg, respectively. Compounds 1a and 1b significantly reduced body weight gain as well as food and water intake in mice. δ-Aminolevulinate dehydratase (δ-ALA-D) and catalase activities were inhibited in mice which received the highest dose of compounds 1a or 1b. Exposure to compounds 1a, 1b and 1c did not modify lipid peroxidation, vitamin C levels, cerebral Na +/K +-ATPase activity and the biochemical parameters evaluated. The important point for medicinal chemistry is that the structural modifications are not introducing toxicity for the compounds in mice.

A Single High Dose of Ascorbic Acid and Iron Is Not Correlated with Oxidative Stress in Healthy Volunteers

Fe (II) is a potential prooxidant in vivo and can induce cellular oxidative stress. Ascorbic acid (AA) is a powerful physiological antioxidant and, in the presence of free Fe (II), can exhibit prooxidant effects in vitro. However, in vivo prooxidant effects of Fe (II) and AA have not yet been indisputably demonstrated. Here we evaluate the potential toxic effect of supplementation of Fe (II) associated with AA. Nine healthy, nonsmoking male volunteers (20–31 years old) participated in the crossover study design. The volunteers were supplemented with either a dose of 2 g of AA, 150 mg of iron carbonyl or 2 g of AA plus 150 mg of iron carbonyl with a washout period of 15 days between each treatment. AA, iron, ferritin, thiobarbituric acid-reactive substances, catalase, δ-aminolevulinic dehydratase and SH thiol groups were measured in the blood of the volunteers. Plasma AA levels were increased at 2, 5 and 24 h after AA or AA plus iron ingestion. Plasma Fe levels were increased at 2 and 5 h in the AA plus iron group. Erythrocyte malondialdehyde levels decreased at 5 and 24 h after AA and 5 h after AA plus iron ingestion. Catalase activity from erythrocytes was increased 5 h after supplementation with AA plus iron. There was no significant difference between groups in the other biochemical parameters evaluated. Thus, the present study does not support the hypothesis that the combination of high plasma concentrations of AA and iron, or iron alone, could cause in vivo oxidative damage after a single supplementation dose.

Butane-2,3-dionethiosemicarbazone: An oxime with antioxidant properties

Oximes are compounds generally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). The aim of this study was to examine the capacity of the butane-2,3-dionethiosemicarbazone oxime to scavenge different forms of reactive species (RS) in vitro, as well as counteract their formation. The potential antioxidant and toxic activity of the oxime was assayed both in vitro and ex vivo. The obtained results indicate a significant hydrogen peroxide (H 2O 2), nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH ) radical scavenging activity at 0.275, 0.5 and 5 μM of oxime, respectively ( p ≤ 0.05). The oxime exhibited a powerful inhibitory effect on dihydroxybenzoate formation (25 μM) ( p ≤ 0.05) and also decreased deoxyribose degradation induced by Fe 2+ and via Fenton reaction (0.44 and 0.66 mM, respectively) ( p ≤ 0.05). The oxime showed a significant inhibitory effect on σ-phenantroline reaction with Fe 2+ (0.4 mM) suggesting a possible interaction between the oxime and iron. A significant decrease in the basal and pro-oxidant-induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo ( p ≤ 0.05). In addition, in our ex vivo experiments the oxime did not depict any significant changes in thiol levels of liver, kidney and brain as well as did not modify the δ-aminolevulinate dehydratase (δ-ALA-D) activity in these tissues. Taken together our results indicate an in vitro and ex vivo antioxidant activity of the oxime possibly due to its scavenging activity toward different RS and a significant iron interaction.

Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese

Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25 mg/mL of MnCl 2 in their drinking water. MnCl 2 intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, δ-aminolevulinate dehydratase (δ-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and 45Ca 2+ influx into striatal slices was decreased in rats exposed to 25 mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased 45Ca 2+ influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia.