Δ-aminolevulinic Dehydratase Research Articles

Hypertension strengthens δ-ALA-D activity inhibition and increases it reactivation index in type 2 diabetic patients

AimsTo assess the effect of hypertension on δ-aminolevulinate dehydratase (δ-ALA-D) activity of type 2 diabetic patients (T2DM). Methodsδ-ALA-D activity and reactivation index, as well as markers of oxidative stress, biochemical and anthropometrics parameters were determined in T2DM (n=23), type 2 diabetic patients with hypertension (T2DM/HT) (n=30) and controls (n=30). ResultsT2DM/HT presented a greater inhibition of δ-ALA-D activity, a higher reactivation index (p<0.05) and a greater depletion of plasma protein thiol groups (P-SH) when compared to T2DM. Moreover, δ-ALA-D activity was positively associated with SH groups and negatively associated with serum protein carbonyl (PC) while its reactivation index was negatively associated with SH groups and positively associated with PC. ConclusionsThese results point out that there is a possible interference of hypertension on the mechanism of the δ-ALA-D activity suggesting that this condition aggravated the oxidative stress of diabetes mellitus.

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.

P-Methoxyl-diphenyl diselenide protects against cisplatin-induced renal toxicity in mice

The present study was designed to investigate the effects of p-methoxyl-diphenyl diselenide (OMePhSe)2 on oxidative stress and renal damage parameters of mice exposed to cisplatin. (OMePhSe)2 (50 and 100mg/kg/day) was orally administered to mice for six consecutive days. On the third day after the beginning of (OMePhSe)2 treatment, the renal toxicity was induced by injecting cisplatin (10mg/kg intraperitoneal) in mice. (OMePhSe)2 treatment (50mg/kg) partially reduced plasma urea and creatinine levels increased by cisplatin. Histopathological examination of kidneys showed that (OMePhSe)2 ameliorated renal injury caused by cisplatin. (OMePhSe)2 attenuated the decrease in reduced glutathione (GSH) and ascorbic acid (AA) levels, the inhibition of glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and catalase (CAT) activities caused by cisplatin in kidney. (OMePhSe)2 treatment partially protected against the inhibition of renal δ-aminolevulinic dehydratase (δ-ALA-D) activity caused by cisplatin. No alteration in renal lipid peroxidation levels was found in cisplatin and/or (OMePhSe)2 groups. (OMePhSe)2 was effective against the increase in reactive species (RS) levels caused by the cisplatin exposure. Based on the renoprotective and antioxidant actions of (OMePhSe)2 we suggest that this organoselenium compound could be considered a feasible candidate to protect against toxicity commonly encountered in cisplatin exposure.

Effects of butane-2,3-dione thiosemicarbazone oxime on testicular damage induced by cadmium in mice

Our group of studies investigated the action of butane-2,3-dione thiosemicarbazone oxime against the testicular damage caused by cadmium chloride (CdCl(2)) in mice. Mice received a single injection of CdCl(2 )(5 mg/kg, intraperitoneally) and, after thirty minutes, the oxime (10 mg/kg, subcutaneously) was administered. Twenty four hours after the last administration, the animals were killed by cervical dislocation and the testes and serum were removed for analysis. The parameters determined were δ-aminolevulinate dehydratase (δ-ALA-D), myeloperoxidase (MPO), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities. The levels of thiobarbituric acid-reactive substances (TBARS), nonprotein thiols (NPSH), ascorbic acid, cadmium and testosterone were also determined. In addition, histological analysis and cytokines quantification (IL-1, IL-6, IL-10, TNF-α and IFN-γ) were performed. Our results demonstrated that the oxime was effective in restoring the inhibition in δ-ALA-D activity induced by CdCl(2). The activation of MPO and increase in IL-1, IL-6, TNF-α and IFN-γ levels induced by CdCl(2) were also reduced by oxime. IL-10, which was reduced by cadmium, was restored by oxime administration. In addition, the oxime was effective in restoring the increase in TBARS levels and the reduction on NPSH levels induced by CdCl(2). Our results demonstrated that oxime was effective in containing the histological alterations induced by CdCl(2). In addition, oxime was able to increase the testosterone levels, reduced by cadmium exposure. In conclusion, the oxime tested was effective in reducing the testicular damage induced by CdCl(2) in mice. The beneficial effects of this oxime are related to its antioxidant and anti-inflammatory action.

Kinetics of Alloxan-Induced Inhibition on δ-Aminolevulinate Dehydratase Activity in Mouse Liver Homogenates

This study evaluated the effects of alloxan on the kinetics properties of the δ-aminolevulinate dehydratase (δ-ALA-D) using mouse liver homogenates. δ-ALA-D is an important sulfhydryl enzyme that catalyses the second step in heme biosynthesis and is commonly diminished in experimental and human diabetes. Despite the known effects of alloxan in models of experimental diabetes, there are no data in the literature demonstrating the effects of alloxan on the kinetics properties of the δ-ALA-D. The results showed that alloxan (1.25-20 μM) caused a concentration-dependent inhibition of hepatic δ-ALA-D activity. The inhibition constant (K(i)) for alloxan-induced inhibition on δ-ALA-D was 3.64 μM. The alloxan (5 μM) caused a decrease in V(max) (65.8%) and in K(m) (53.1%), which is suggestive of an uncompetitive inhibition of enzyme. In addition, dithiothreitol (700 and 1,000 μM) completely prevented the δ-ALA-D activity inhibition induced by 10 and 20 μM alloxan. Similar protection was obtained in the presence of 2,000 μM glutathione. Therefore, this work showed that the inhibition of hepatic δ-ALA-D activity can be obtained in vitro at low micromolar levels of alloxan, and can also be prevented by reducing agents. Moreover, these results may help to understand the abnormalities in heme pathway found in models of experimental diabetes in vivo.

Evaluation of toxic effects of a diet containing fish contaminated with methylmercury in rats mimicking the exposure in the Amazon riverside population

This study was designed to evaluate the effects of a diet rich in fish contaminated with MeHg, mimicking the typical diet of the Amazon riverside population, in rats. Animals were randomly assigned to one of three groups with eight rats in each group: Group I—control, received commercial ration; Group II—received a diet rich in uncontaminated fish; Group III—received a diet rich in fish contaminated with MeHg. Treatment time was 12 weeks. Oxidative stress markers were evaluated, as well as the effects of this diet on DNA stability, systolic blood pressure (SBP), nitric oxide (NO) levels and histological damage in different tissues. There was a significant increase in SBP values in rats fed with MeHg-contaminated fish diet after the 10th week of the treatment. As far as oxidative stress biomarkers are concerned, no differences were observed in reduced glutathione and protein carbonyl levels, glutathione peroxidase, catalase, superoxide dismutase or δ-aminolevulinate dehydratase activities between the groups of animals receiving contaminated and uncontaminated fish diets. On the other hand, malondialdehyde levels increased significantly in rats fed with contaminated fish. NO levels were similar in all groups. DNA migration showed augmented in rats exposed to contaminated fish and histopathological analyses showed weak but significant leukocyte infiltration. Thus, we conclude that the MeHg-contaminated fish diet induced a slight lipid peroxidation and genotoxicity. However, these effects seem to be much less pronounced than when rats are exposed to aqueous solution containing CH3HgCl.Our findings support the contention that the chemical form of MeHg in fish or fish nutrients such as polyunsaturated fatty acids, Se or vitamin E could minimize the toxic effects of MeHg exposure in fish-eating communities.

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood

Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead-exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ-aminolevulinate dehydratase (δ-ALA-D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ-ALA-D activity was inhibited only in battery workers, whereas the δ-ALA-D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = -0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione-S-transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead- and cadmium-exposed populations. However, lead-associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re-evaluating the recommended health-based limits in occupational exposure to this metal.

N-acetylcysteine on oxidative damage in diabetic rats

N-acetylcysteine (NAC) is a potent mucolitic agent and also an antioxidant. Its antioxidant action is due to its ability to stimulate reduced glutathione (GSH) synthesis, therefore maintaining intracellular levels. The aim of this study was to evaluate the effects of NAC administered intraperitoneally (i.p.) in a decreasing of oxidative tissue damage in the liver and kidney of alloxan-induced diabetic rats, especially on thiolic groups (nonproteic and proteic groups). Adult male Wistar rats (200–350 g) were used; diabetes was induced accordingly by a single i.p. injection of alloxan monohydrate, and the control group received a similar volume of the vehicle. Lipid peroxidation (LPO) biomarker (malondialdehyde; MDA), δ-ALA-D activity, GSH, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were quantified to assess the oxidative stress. All tests were performed in tissue homogenates. Creatinine, urea, aspartate transaminase, and alanine transaminase were determined by commercial kits, using serum samples. A significant decrease in LPO (i.e., hepatic and renal) and an increase in δ-aminolevulinate dehydratase activity, especially in the renal tissue, were observed. Also, NAC at 75 mg/kg showed more effective restoration of oxidative stress biomarkers than NAC at 25 mg/kg. Our findings suggest that NAC can be used as an antioxidant agent in diabetes, exhibiting modulatory action on the oxidative stress biomarkers analyzed in this work. Moreover, these findings can contribute to others’ research, regarding the utilization of NAC to ALA-D activity restoration in the kidneys.

δ-Aminolevulinate dehydratase activity in type 2 diabetic patients and its association with lipid profile and oxidative stress

ObjectivesTo investigate the activity of δ-Aminolevulinate dehydratase (δ-ALA-D) and its possible relationship with oxidative status, lipid profile, body mass index (BMI) in type 2 diabetics (DM2) patients. Design and methodsδ-ALA-D activity and reactivation index, as well as markers of oxidative stress and biochemical and anthropometrics parameters were determined in DM2 patients (n=63) and controls (n=63). ResultsThere was a decreased δ-ALA-D activity and a higher reactivation index (p<0.05) in DM2 patients besides an elevated level of oxidative stress. Disturbances on lipid profile were related to the enzymatic activity and BMI also was correlated with oxidative level in DM2 patients (p<0.05). ConclusionThere is an association between oxidative stress, abnormalities on lipid profile, distribution of body fat and δ-ALA-D activity inhibition as well as the enzyme is more oxidized in the DM2 suggesting that it would be a good biomarker for assessing prejudice in chronic metabolic processes.

The role of the glutathione system in seizures induced by diphenyl diselenide in rat pups

The present study investigated the role of the glutathione system in seizures induced by diphenyl diselenide (PhSe)2 (50mg/kg) in rat pups (post natal day, 12–14). Reduced glutathione (GSH) (300nmol/site; i.c.v.), administered 20min before (PhSe)2, abolished the appearance of seizures, protected against the inhibition of catalase and δ-aminolevulinic dehydratase (δ-ALA-D) activities and increased glutathione peroxidase (GPx) activity induced by (PhSe)2. Administration of l-buthionine sulfoximine (BSO, a GSH-depleting compound) (3.2μmol/site; i.c.v.) 24h before (PhSe)2 increased the percentage (42–100%) of rat pups which had seizure episodes, reduced the onset for the first convulsive episode. In addition, BSO increased thiobarbituric acid reactive species (TBARS) levels and decreased GSH content, catalase, δ-ALA-D and Na+, K+-ATPase activities. Treatment with sub effective doses of GSH (10nmol/site) and d-2-amino-7-phosphonoheptanoic acid (AP-7, an antagonist of the glutamate site at the NMDA receptor; 5mg/kg, i.p.) abolished the appearance of seizures induced by (PhSe)2 in rat pups. Sub effective doses of GSH and kynurenic acid (an antagonist of strychnine-insensitive glycine site at the NMDA receptor; 40mg/kg, i.p.) were also able in abolishing the appearance of seizures induced by (PhSe)2. In conclusion, administration of GSH protected against seizure episodes induced by (PhSe)2 in rat pups by reducing oxidative stress and, at least in part, by acting as an antagonist of glutamate and glycine modulatory sites in the NMDA receptor.

Neuropharmacological effects of lipoic acid and ubiquinone on δ‐aminolevulinic dehydratase, Na+, K+‐ATPase, and Mg2+‐ATPase activities in rat hippocampus after pilocarpine‐induced seizures

In this study, we investigated the effects of lipoic acid (LA) in the hippocampus oxidative stress caused by pilocarpine-induced seizures in adult rats. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10mg/kg, i.p., LA group), ubiquinone [20mg/kg, i.p., ubiquinone (UQ) group], pilocarpine (400mg/kg, i.p., P400 group), and the association of LA (10mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.) or UQ (20mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.), 30min before of administration of P400 (LA plus P400 group and UQ plus P400 group, respectively). After the treatments, all groups were observed for 1h. The enzyme activities (δ-aminolevulinic dehydratase (δ-ALA-D), Mg(2+) -ATPase, and Na(+) , K(+) -ATPase) were measured using spectrophotometric methods, and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA and UQ were also evaluated on the same parameters. We reported here for the first time that Na(+) , K(+) -ATPase and δ-ALA-D activities inhibition and Mg(2+) -ATPase stimulation in the pilocarpine model are probably attributed to the oxidative stress caused by seizures in the rat hippocampus. The addition of the antioxidants LA and UQ may reverses the previously mentioned Na(+) , K(+) -ATPase and δ-ALA-D inhibitions and Mg(2+) -ATPase stimulation. The oxidative stress plays an important signaling role in pilocarpine-induced seizures, and antioxidant drugs might be considered as therapeutical tools in this pathology.

Diphenyl diselenide potentiates nephrotoxicity induced by mercuric chloride in mice

Following our long-standing interest in the mechanisms involved in selenium toxicity, the aim of this work was to extend our previous studies to gain a better understanding of mercuric chloride (HgCl₂) + diphenyl diselenide (PhSe)₂ toxicity. Mice received one daily dose of HgCl₂ (4.6 mg kg(-1) , subcutaneously) for three consecutive days. Thirty minutes after the last injection of HgCl₂, mice received a single dose of (PhSe)₂ (31.2 mg kg(-1) , subcutaneously). Five hours after (PhSe)₂ administration, mice were euthanized and δ-aminolevulinate dehydratase, catalase (CAT), glutathione S-transferase (GST) and Na(+) , K(+) -ATPase activities as well as thiobarbituric acid-reactive substances (TBARS), ascorbic acid and mercury levels were determined in kidney and liver. Parameters in plasma (urea, creatinine, protein and erythropoietin), whole blood (hematocrit and hemoglobin) and urine (protein) were also investigated. HgCl₂ + (PhSe)₂ exposure caused a decrease in renal GST and Na(+) , K(+) -ATPase activities and an increase in renal ascorbic acid and TBARS concentrations when compared with the HgCl₂ group. (PhSe)₂ potentiated the increase in plasma urea caused by HgCl₂. HgCl₂ + (PhSe)₂ exposure caused a reduction in plasma protein levels and an increase in hemoglobin and hematocrit contents when compared with the HgCl₂ group. There was a significant reduction in hepatic CAT activity and an increase in TBARS levels in mice exposed to HgCl₂ + (PhSe)₂ when compared with the HgCl₂ group. The results demonstrated that (PhSe)₂ did not modify mercury levels in mice. In conclusion, (PhSe)₂ potentiated damage caused by HgCl₂ affecting mainly the renal tissue.

(E)-2-benzylidene-4-phenyl-1,3-diselenole has antioxidant and hepatoprotective properties against oxidative damage induced by 2-nitropropane in rats

The in vitro effect of (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD) was evaluated through iron/EDTA-induced thiobarbituric acid reactive species (TBARS) and reactive species (RS) determinations as well as of the scavenging 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical quantification. BPD at the concentrations of 10 and 50 μΜ decreased RS and TBARS levels, respectively. The antioxidant activity was not related to the scavenging DPPH radical mechanism. A second objective of this study was to investigate the hepatoprotective action of BPD, administered by oral route, against oxidative damage induced by 2-nitropropane (2-NP) (100 mg/kg of body weight) in liver of rats. At the dose of 50 mg/kg, BPD protected against the increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities induced by 2-NP. BPD (10 and 50 mg/kg) protected against the increase in TBARS levels and alkaline phosphatase (ALP) activity. Sections of liver from 2-NP-exposed rats presented intense infiltration of inflammatory cells and loss of cellular architecture. BPD (10 and 50 mg/kg) attenuated 2-NP-induced hepatic histological alterations. The inhibition of δ-aminolevulinic dehydratase (δ-ALA-D), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) activities and the decreased GSH levels caused by 2-NP were protected by BPD (50 mg/kg). Catalase activity and ascorbic acid levels were not altered by 2-NP. These results demonstrated the antioxidant and hepatoprotective effects of BPD in liver of rats.

Lead and essential trace element levels in school children: A cross-sectional study

Background: Nutritional status is thought to modulate susceptibility to lead (Pb) toxicity. The type and nature of these interactions needs to be investigated.Aim: To assess the prevalence of sub-clinical Pb toxicity (defined by ≥ 10 μ_rm;g/dL blood levels) and trace element deficiencies (Iron (Fe), Zinc (Zn), Copper (Cu) and Magnesium (Mg)) and to find out their possible relationship, if any.Subjects and methods: A cross-sectional survey was carried out in a total of 195 school children residing in urban (n = 65), urban heavy traffic (n = 65) and urban industrial (n = 65) zones of Hyderabad, India. Blood Pb, trace element levels, haemoglobin and δ-aminolevulinate dehydratase (δ-ALAD) activity was measured.Results: High blood lead levels ( ≥ 10 μ_rm;g/dL) were observed in 54.3% of children while percentage prevalence of trace element deficiencies such as Fe (16.2%), Zn (68.6%), Mg (41.7%) and Cu (25%) were also high in children included in the study. Higher blood Pb levels and reduced δ-ALAD activity was observed in children residing in heavy traffic and industrial areas. Blood Pb levels but not δ-ALAD activity correlated inversely with serum Fe in heavy traffic and industrial children, respectively. Interestingly, δ-ALAD activity but not blood Pb levels correlated inversely with trace element levels only in urban children.Conclusions: These results suggest higher prevalence of sub-clinical Pb toxicity and trace element deficiencies in urban children. Further, high blood Pb levels appear to be correlated with reduced δ-ALAD activity and iron status in Pb exposed children.

Inhibition of hepatic δ-aminolevulinate dehydratase activity induced by mercuric chloride is potentiated by N-acetylcysteine in vitro

Mercuric chloride (HgCl)2 is a toxic metal that causes oxidative damage in several tissues. N-acetylcysteine (NAC) is a sulfhydryl compound with antioxidant activity. In the present study, we investigated the in vitro effects of the association between HgCl2 and NAC in tissues of mice. For this purpose, we evaluated the in vitro effect of HgCl2+NAC association on δ-aminolevulinate dehydratase (δ-ALA-D) activity and on thiobarbituric acid reactive substances (TBARS) levels in liver and kidney of mice. The results demonstrate that HgCl2 inhibited δ-ALA-D activity in both tissues. Hepatic δ-ALA-D activity inhibited by HgCl2 was potentiated by the highest concentration of NAC. The inhibition of hepatic δ-ALA-D activity seems to be related to sulfhydryl groups oxidation of the enzyme. We observed also that HgCl2 increased TBARS levels in kidney and liver. Hepatic TBARS levels were reduced by NAC, at higher concentration. In contrast, NAC, at higher concentration, increased renal TBARS levels. In conclusion, the inhibition of hepatic δ-aminolevulinate dehydratase activity induced by HgCl2 is potentiated by NAC in vitro, and this effect is not related to hepatic lipid peroxidation.

Acute exposure of rabbits to diphenyl diselenide: a toxicological evaluation

The simple organoselenium compound diphenyl diselenide (PhSe)(2) is a promising new pharmacological agent. However, few toxicological evaluations of this molecule have been reported. We evaluated the effects of acute administration of (PhSe)(2) on toxicological parameters in rabbits. Adult New Zealand rabbits were exposed to (PhSe)(2) (5-500 micromol kg(-1) , intraperitoneally) once a day for 5 days. Exposure to 500 micromol kg(-1) caused 85% mortality. Exposure to 50 micromol kg(-1) of (PhSe)(2) increased the glutathione levels in the hippocampus, kidney, heart, muscle and blood, whereas lipoperoxidation (TBARS) decreased in the cerebellum and kidney after exposure to 5 micromol kg(-1) . The activity of glutathione peroxidase increased in the heart and muscle of rabbits treated with 50 micromol kg(-1) of (PhSe)(2) and glutathione reductase activity was reduced in the cerebellum, cerebral cortex and kidney. Treatment with (PhSe)(2) reduced the activity of δ-aminolevulinate dehydratase in the hippocampus and increased this activity in the heart, but did not alter the activity of complexes I and II of the respiratory chain in the liver and brain. Hepatic and renal biochemical and histological parameters were not modified by (PhSe)(2) and apoptosis was not detected in these tissues; however, the hepatic cells tended to accumulate fat vacuoles. These results indicated that acute toxicology to (PhSe)(2) in rabbit is dependent on the dose, which should motivate further experiments on the therapeutic properties of this compound.

Anticonvulsant effect of (E)-2-benzylidene-4-phenyl-1,3-diselenole in a pilocarpine model in mice

Aim This study investigated the in vitro antioxidant activity of (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD), the anticonvulsant effect of BPD on seizures induced by pilocarpine (PC), pentylenetetrazole (PTZ) and 4-aminopyridine (4-AMP) and the mechanism involved. Methods BPD antioxidant activity in vitro was investigated using sodium nitroprusside (SNP) and malonate-induced thiobarbituric acid reactive species (TBARS) and sodium azide-induced reactive species (RS) production. Thiol peroxidase and oxidase as well as δ-aminolevulinate dehydratase (δ-ALA-D) activities were examined. Mice were pretreated via oral route (p.o.) with BPD (1–100 mg/kg) before intraperitoneal (i.p.) administration of PC (400 mg/kg), PTZ (80 mg/kg) or 4-AMP (12 mg/kg). To investigate the antioxidant effect of BPD on oxidative stress induced by PC, the activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase (CAT) as well as the levels of RS and TBARS were determined in brains of mice. δ-ALA-D, acetylcholinesterase (AChE) and Na + , K + ATPase activities were verified. Key findings BPD (5 μM) reduced RS production and lipid peroxidation induced by SNP and malonate. BPD (1–50 μM) did not show thiol peroxidase and oxidase activities and did not alter δ-ALA-D activity. BPD (5 mg/kg) increased the latency to the seizure onset on PTZ and 4-AMP models. BPD (100 mg/kg) abolished seizures and death induced by PC in mice. BPD protected against the increase in RS and TBARS levels. The activity of Na +, K + ATPase and AChE inhibited by PC remained unaltered in the BPD group. Significance BPD showed anticonvulsant and antioxidant effects on seizures induced by PC in mice.

Effects of low-level exposure to xenobiotics present in paints on oxidative stress in workers

Paints are composed of an extensive variety of hazardous substances, such as organic solvents and heavy metals. Biomonitoring is an essential tool for assessing the risk to occupational health. Thus, this study analyzed the levels of biomarkers of exposure for toluene, xylene, styrene, ethylbenzene, and lead, as well as the oxidative stress biomarker alterations in painters of an industry. Lipid peroxidation biomarker (MDA), δ-aminolevulinate dehydratase (ALA-D), nonprotein thyol groups, superoxide dismutase and catalase (CAT) were analyzed in exposed and nonexposed subjects. We estimated which of the paint constituents have the greatest influence on the changes in the biomarkers of oxidative stress in this case of co-exposure. The results demonstrated that despite the fact that all the biomarkers of exposure were below the biological exposure limits, the MDA levels and antioxidant enzyme activities were increased, while nonprotein thyol groups and ALA-D levels were decreased in painters when compared with nonexposed subjects. After statistic test, toluene could be suggested as the principal factor responsible for increased lipid peroxidation and inhibition of ALA-D enzyme; however, further studies on the inhibition of ALA-D enzyme by toluene are necessary.

Dexmedetomidine protects blood δ-aminolevulinate dehydratase from inactivation caused by hyperoxygenation in total intravenous anesthesia

Delta-aminolevulinate dehydratase (δ-ALA-D) enzyme is sensitive to pro-oxidant agents, including molecular oxygen. Here, we tested whether hyperoxygenation after total intravenous (i.v.) anesthesia could interact with the type of anesthesia (dexmedetomidine, continuous infusion; 0.5 μg/kg/h or remifentanil, continuous infusion; 0.3 μg/kg/min) plus propofol using blood δ-ALA-D activity and thiobarbituric acid reactive substances (TBARS) levels as ending points of toxicity. In absence or presence of dithiothreitol (DTT), δ-ALA-D activity was reduced after hyperoxygenation in the group treated with remifentanil and was not modified in dexmedetomidine group. TBARS increased considerably in the blood of both groups of patients after oxygenation. The results obtained here suggest that the hyperoxygenation was associated with a marked increase in TBARS production regardless of the type of anesthesia. δ-ALA-D activity was only inhibited in remifentanil group, which indicates a possible interaction between oxygenation and the type of anesthetic. This is the first demonstration that dexmedetomidine may protect blood δ-ALA-D from oxidation. However, further studies are necessary to establish a possible antioxidant role of dexmedetomidine against hyperoxygenation in human blood.

Association between diphenyl diselenide and cadmium chloride attenuates the toxicity of both in tissues of mice in vitro

The in vitro effect of association between cadmium chloride (CdCl 2) and diphenyl diselenide (PhSe) 2 was investigated. Mouse liver, kidney and testes were used to evaluate δ-aminolevulinate dehydratase (δ-ALA-D) activity and thiobarbituric acid-reactive substances (TBARS) levels. CdCl 2 and (PhSe) 2, at different concentrations, caused an inhibition in δ-ALA-D activity of liver, kidney and testes. The inhibitory effect of (PhSe) 2 in hepatic and renal δ-ALA-D activity was attenuated by interaction of this compound with CdCl 2 at non-inhibitory concentration. Dithiothreitol (DTT), but not ZnCl 2, restored the inhibition observed in δ-ALA-D activity in all tissues. This suggests an involvement of sulfhydryl groups in δ-ALA-D inhibition. TBARS levels were increased by CdCl 2 in all tissues and (PhSe) 2 was able to abolish this increase. The results demonstrate that the association between CdCl 2 and (PhSe) 2 attenuates the toxicity of both compounds and the possible mechanisms of this protection are due to complex formation between cadmium and selenium and involves the antioxidant activity of (PhSe) 2.