Delta-aminolevulinic Dehydratase Activity Research Articles

Enzymatic antioxidant defense system and ALA-D enzyme activity in soybean Enlist™ line

Enlist™ technology confers resistance to 2,4-D herbicides, glyphosate, and ammonium glufosinate for soybeans. However, the application of herbicides to plants can generate stress, even in resistant crops. Thus, here we evaluated whether the application of herbicides in transgenic soybean farms, resistant to these herbicides, adversely affects the activity of antioxidant enzymes and porphobilinogen formation by delta-aminolevulinate dehydratase (ALA-D) activity. At seven days after herbicide application, the aerial part of the plants was collected and used to determine the activity of antioxidant enzymes as catalase, ascorbate peroxidase, and guaiacol peroxidase, such as lipid peroxidation levels and the activity of the ALA-D enzyme. At seven days after herbicide application, the aerial part of plants was collect and used to determine the activity of antioxidant enzymes, such as catalase, ascorbate peroxidase and guaiacol peroxidase, as well as the levels of lipid peroxidation and the activity of the ALA-D enzyme. The activity of important antioxidant enzymes involved in the scavenging of reactive oxygen species (ROS) was increased in the soybean cultivar with the Enlist™ technology, while no severe damage to lipids was detected. However, the activity of ALA-D was inhibited, which could potentially impair the formation of porphobilinogen and decrease photosynthetic efficiency. Thus, these results indicate that herbicides can affect the activity of ROS-scavenging enzymes even in transgenic, herbicide-resistant plants.

BIOMONITORING OF A POPULATION RESIDING NEAR TO MINE TAILINGS IN GUANAJUATO, MEXICO

Some metals present in residues coming from mining activities can damage DNA. A preliminary evaluation was carried out to determine the genotoxic effects on a resident population from a mining area in Xichú, Guanajuato, Mexico. Blood lead levels (BLL), and arsenic levels in urine (AsU), were measured as biomarkers of exposure. Hematological damage was evaluated trough hematocrit, hemoglobin and activity of enzyme delta-aminolevulinic dehydratase (δ-ALAD). DNA damage in blood cells was evaluated by comet assay. BLL (7.5 ± 1.2 and 7.9 ± 3.3 μg/dL) and AsU (25.2 ± 15.8 and 18.3 ± 18.4 μg/g creatinine) were found in children and adults, respectively. Of the children and adults, 100 and 91.7 %, respectively had levels of enzyme activity below 20 U/L erythrocytes. Regarding DNA damage, the children showed an Olive tail moment of 5.0 ± 1.6 and a tail length of 40.9 ± 4.9 μm, of similar magnitude than adults (4.6 ± 1.0 and 41.8 ± 5.9 μm, respectively). In conclusion, this preliminary study describes the health risk scenario of population near the mine, nevertheless, more studies are needed in the area.

Delta-aminolevulinate dehydratase activity and oxidative profile in pregnant women with pre-gestational type 2 diabetes and gestational diabetes

The aim of this study was to perform a comparative evaluation between pregnant women: healthy, with pre-gestational type 2 diabetes (T2DM) and gestational diabetes mellitus (GDM), to determine if diabetes mellitus developed at different times interferes with the oxidative impact on the pregnant woman maternal body. A total of 90 pregnant women were recruited in the third trimester of pregnancy, subdivided into the three groups, and evaluated through their clinical characteristics, oxidative stress markers and delta-aminolevulinate dehydratase (δ-ALA- D) activity. Pregnant women with diabetes mellitus (DM) showed an increase in: age, pre-gestational and gestational body mass index (BMI), blood pressure, blood glucose and platelet count; those with T2DM had higher pre-gestational BMI and glycated hemoglobin A1c (HbA1c). The levels of thiobarbituric acid reactive substances were higher and the levels of non-protein thiols and catalase activity were lower in the DM groups compared to the control. Vitamin C was decreased in the T2DM group. The δ-ALA-D activity was decreased in pregnant women with GDM and the rate of enzymatic reactivation was higher in the DM groups. DM presented in gestation, regardless of the moment of its development, generates increase of the oxidative stress and decrease of the antioxidant defences, representing the largest difference with the control group. It is suggested that the insulin used in the treatment of T2DM acts in a beneficial way in the δ-ALA-D activity.

Delta-Aminolevulinate dehydratase and glutathione peroxidase activity in Alzheimer's disease: a case-control study.

Alzheimer's disease (AD) is a neurodegenerative pathology that affects elderly people all over the world. Several studies have demonstrated that oxidative stress is an aggravating factor for AD development and progression. Therefore, this study aimed to evaluate the activity of two oxidative stress markers, glutathione peroxidase (GPx) and δ-aminolevulinate dehydratase (δ-ALA-D), as well as correlate them with blood metal levels and AD progression. For this purpose, 88 elderly individuals were divided in two groups: AD group (34 patients diagnosed with AD) and control group (34 subjects paired by age with the AD group). The Mini-Mental State Examination and the Clinical Dementia Rating (CDR) were used as tools to classify the AD progression. GPx and δ-ALA-D activities were measured in all subjects through blood tests. Both enzymes' activities were decreased in AD patients when compared to the age-matched control group, regardless of the CDR. Moreover, GPx activity was positively correlated with selenium levels in the blood; and the δ-ALA-D activity was negatively correlated with blood copper levels. Taken together, our results indicated that, for the first time, blood δ-ALA-D activity was significantly inhibited in AD patients. While literature reports conflicting data regarding GPx activity in AD patients, the δ-ALA-D activity seems to be a more consistent tool to be applied as an earlier AD marker.

Evaluation of oxidative stress and δ-aminolevulinate dehydratase activity in twin pregnancies

Purpose: To assess and understand the maternal oxidative stress in twin pregnancies, currently not studied, through ascertain indicators of oxidative damage in maternal blood in response of two fetuses, as well as the relation of placenta with or without the increase of oxidative stress in these gestations. Materials and methods: The activity of delta-aminolevulinate dehydratase (δ-ALA-D) was analyzed as an indirect marker of oxidative stress, as well as the quantification of thiobarbituric acid reactive substances (TBARS), protein thiol groups (P-SH) and nonprotein thiol groups (NP-SH), vitamin C (VIT C) and catalase activity (CAT) in maternal blood samples from twin (n = 30) and single (n = 30) pregnancies. This study was approved by the Human Ethics Committee UFSM (register by the number 49823015.4.0000.5346). Results: TBARS was significantly higher in twin pregnancies, while thiol groups, VIT C and CAT were decreased, asides from the reduced activity of δ-ALA-D in comparison to single fetus gestations. Conclusions: The study established an oxidative stress increased and an antioxidant ability decreased in twin pregnancies, suggesting a possible relation between the levels of oxidants and antioxidants with the complications in those gestations.

Longitudinal Study of Delta-Aminolevulinate Dehydratase Activity and Oxidative Profile in Healthy Pregnant Women.

Pregnancy is characterized by changes in various organs, triggering changes in the use of energy substrates and increased oxygen consumption. In addition, gestation is an oxidative event that can be assessed by the relationship between free radicals and antioxidants produced by the body. Excessive production of free radicals has detrimental effects such as damage to enzymes, carbohydrates, and DNA. Thus, the objective of this study was to evaluate the oxidative status and antioxidant responses throughout pregnancy through a longitudinal study. Reactive oxygen species were analyzed by means of thiobarbituric acid reactive substances and nitric oxide, the antioxidant system through vitamin C, sulfhydryl groups, total antioxidant capacity, and ferric reducing ability of plasma as well as enzymes such as catalase and delta-aminolevulinate-dehydratase in pregnant women in the three gestational trimesters (n = 30). According to the results, the markers of oxidative damage showed significant differences in the different gestational trimesters where they were increased in the second trimester when compared to the first trimester. The antioxidant defenses responded differently in each gestational trimester, suggesting a response pattern to try to combat the damage caused by free radicals, in order to stabilize the increase of oxidative stress caused in the second gestational trimester.

Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity

Lead is an environmental hazard with great public health concern and has been known to inhibit delta-aminolevulinate dehydratase (ALAD) activity involved in the heme biosynthetic pathway. The study aimed to investigate the influence of ALAD polymorphism (G177C) on retention of Pb-B levels and ALAD activity on occupationally exposed lead workers. In the present study, we enrolled 561 lead exposed and 317 non-occupationally exposed subjects and performed a comprehensive analysis of Pb-B levels along with ALAD activity and genotyping. The frequency of ALAD variants observed in the total subjects (n = 878) was 70.04% for ALAD 1-1, 27.44% for heterozygous ALAD 1–2 and 2.5% for homozygous mutant ALAD 2-2. Our study revealed that ALAD 1–2 carriers presented higher Pb-B levels compared to wild type ALAD 1-1 carriers. Further, a significant difference was observed in the activity of ALAD between ALAD 1–2/ 2-2 and ALAD 1-1 carriers of non-occupationally exposed group indicating that the polymorphic nature of the enzyme may contribute to altered activity of ALAD irrespective of lead exposure. Hence, ALAD 2 allele might contribute to increased susceptibility to high Pb-B retention, and genotyping of ALAD in lead exposed subjects might be used as a prediction marker to impede tissue/organ damage due to lead toxicity.

Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) with extracorporeal circulation produces changes in the immune system accompanied by an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokines. We hypothesize that dexmedetomidine (DEX) as an anesthetic adjuvant modulates the inflammatory response after coronary artery bypass graft surgery with mini-CPB. In a prospective, randomized, blind study, 12 patients (4 females and 8 males, age range 42-72) were assigned to DEX group and compared with a conventional total intravenous anesthesia (TIVA) group of 11 patients (4 females and 7 males). The endpoints used to assess inflammatory and biochemical responses to mini-CPB were plasma interleukin (IL)-1, IL-6, IL-10, interferon (INF)-γ, tumor necrosis factor (TNF)-α, C-reactive protein, creatine phosphokinase, creatine phosphokinase-MB, cardiac troponin I, cortisol, and glucose levels. These variables were determined before anesthesia, 90 min after beginning CPB, 5 h after beginning CPB, and 24 h after the end of surgery. Endpoints of oxidative stress, including thiobarbituric acid reactive species and delta-aminolevulinate dehydratase activity in erythrocytes were also determined. DEX+TIVA use was associated with a significant reduction in IL-1, IL-6, TNF-α, and INF-γ (P<0.0001) levels compared with TIVA (two-way ANOVA). In contrast, the surgery-induced increase in thiobarbituric acid reactive species was higher in the DEX+TIVA group than in the TIVA group (P<0.01; two-way ANOVA). Delta-aminolevulinate dehydratase activity was decreased after CPB (P<0.001), but there was no difference between the two groups. DEX as an adjuvant in anesthesia reduced circulating IL-1, IL-6, TNF-α, and INF-γ levels after mini-CPB. These findings indicate an interesting anti-inflammatory effect of DEX, which should be studied in different types of surgical interventions.

Evaluation of Delta-Aminolevulinic Dehydratase Activity, Oxidative Stress Biomarkers, and Vitamin D Levels in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune neurological disorder of unknown etiology. Oxidative stress and alterations in vitamin D levels have been implicated in the pathophysiology of MS. The aim of this study was to investigate δ-aminolevulinate dehydratase (δ-ALA-D) activity as well as the levels of vitamin D, lipid peroxidation levels, carbonyl protein content, DNA damage, superoxide dismutase (SOD) and catalase (CAT) activities, and the vitamin C, vitamin E, and non-protein thiol (NPSH) content in samples from patients with the relapsing-remitting form of MS (RRMS). The study population consisted of 29 RRMS patients and 29 healthy subjects. Twelve milliliters of blood was obtained from each individual and used for biochemical determinations. The results showed that δ-ALA-D and CAT activities were significantly increased, while SOD activity was decreased in the whole blood of RRMS patients compared to the control group (P < 0.05). In addition, we observed a significant increase in lipid peroxidation, carbonyl protein levels in serum and damaged DNA in leucocytes in RRMS patients compared with the control group (P < 0.05). Nonetheless, the levels of vitamin C, vitamin E, NPSH, and vitamin D were significantly decreased in RRMS patients in relation to the healthy individuals (P < 0.05). In conclusion, our results suggested that the increase in δ-ALA-D activity may be related to the inflammatory and immune process in MS in an attempt to maintain the cellular metabolism and reduce oxidative stress. Moreover, the alterations in the oxidant/antioxidant balance and lower vitamin D levels may contribute to the pathophysiology of MS.

Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin

This study evaluated the effects of curcumin and/or insulin on antioxidant enzyme activity in blood, liver, and kidney, as well as on lipid peroxidation and delta aminolevulinic dehydratase (δ-ALA-D) activity, and a histopathological analysis of streptozotocin-induced diabetic rats. The animals were divided into six groups (n=6): control/saline (C); control/curcumin (CCur); diabetic/saline (D); diabetic/insulin (DIns); diabetic/curcumin (DCur); and diabetic/insulin/curcumin (DInsCur). After 30days of treatment with curcumin and/or insulin, the animals were sacrificed and the liver, kidney, and serum were used for experimental determinations. Results of histopathological analysis showed that the treatment with insulin ameliorate renal and hepatic lesions from both DIns and DInsCur groups. TBARS levels were significantly increased in serum, liver, and kidney in D group and the administration of curcumin and insulin prevented this increase in DIns and DCur groups. The activities of catalase (CAT), superoxide dismutase, and δ-ALA-D presented a significant decrease in the liver and kidney D group when compared to C group (P<0.05). The animals treated with curcumin and insulin presented an increase of CAT activity, revealing a positive interaction between both substances. The treatments with curcumin or insulin prevented oxidative stress in blood, through modulation of enzymatic antioxidant defenses. These findings contributed to the comprehension that antioxidants from medicinal plants could be used as adjuvant in the treatment of this endocrinopathy and not as single therapy.

Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model.

We investigated the protective role of ceftriaxone plus sulbactam with VRP1034 (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male rats were divided into three groups of eight rats each. The control group received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body weight) through gastric gavage for 21 days. Group III received CdCl2 and was treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The hematological, biochemical, lipid peroxidation levels and enzymatic parameters were measured in plasma and tissues (brain, liver and kidney) of all groups. The Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde (p<0.001) and myloperoxidase (MPO) levels along with significantly increased hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. Delta aminolevulinate dehydratase (δ-ALAD) activity was significantly (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034 treated group as compared with cadmium exposed group. The levels of hepatic and renal parameters were significantly (p<0.001) decreased in ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. These findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent free radical scavenger and exhibits metal chelating properties that reduce free radical mediated tissue injury and prevent dysfunction of hepatic and renal organs during metal intoxication.

Octabromodiphenyl ether — porphyrogenicity after repeated administration to rats

Octabromodiphenyl ether (OctaBDE) is a flame retardant which has been withdrawn from common use due to its negative effect on the environment. The literature data regarding its toxicity addresses its effect on liver function, the endocrine and reproductive systems, as well as its developmental toxicology aspects. The aim of this study was to investigate the effect of repeated administration of OctaBDE on heme biosynthesis in rats. The study was performed on female Wistar rats. OctaBDE was administered intragastrically at four different doses (2, 8, 40 or 200 mg/kg/day) for 7, 14, 21 or 28 days. The following measures of heme synthesis disturbance were used: urinary excretion of porphyrins, liver concentration of porphyrins, the activity of delta-aminolevulinate synthase (ALA-S) and delta-aminolevulinate dehydratase (ALA-D) in the liver. After 28 days of exposure, lower ALA-S and ALA-D activity was observed in the liver. Additionally, increased concentrations of high carboxylated porphyrins (octa- and heptacarboxyporphyrins) were found in the liver: from 2- to 10-fold after the 2 mg/kg/day doses and from 4- to 14-fold after the 8-200 mg/kg/day doses. The porphyrogenic effect of OctaBDE was also evidenced by augmented, dose-dependent and exposure time-dependent, concentrations of total porphyrins in urine (2-7.5-fold increase) and their urinary excretion (2-9-fold increase). Tetracarboxyporphyrins predominated in the urine; their concentrations increased 2.5-10 fold. The study revealed that repeated exposure to OctaBDE affects heme biosynthesis and the levels of porphyrins. The lowest effective level which induced changes in porphyrin concentration was 2 mg/kg/day.

Delta-aminolevulinate dehydratase activity in red blood cells of rats infected withTrypanosoma evansi

The aim of this study was to evaluate the activity of delta-aminolevulinate dehydratase (δ-ALA-D) in red blood cells of rats infected with Trypanosoma evansi and establish its association with haematocrit, serum levels of iron and zinc and lipid peroxidation. Thirty-six male rats (Wistar) were divided into 2 groups with 18 animals each. Group A was non-infected while Group B was intraperitoneally infected, receiving 7·5×106 trypomastigotes per animal. Each group was divided into 3 subgroups of 6 rats and blood was collected during different periods post-infection (p.i.) as follows: day 5 (A1 and B1), day 15 (A2 and B2) and day 30 PI (A3 and B3). Blood samples were collected by cardiac puncture to estimate red blood cell parameters (RBC), δ-ALA-D activity and serum levels of iron, zinc and thiobarbituric acid reactive substances (TBARS). Rats in group B showed a significant (P<0·05) reduction of RBC count, haemoglobin concentration and haematocrit at days 5 and 15 p.i. The activity of δ-ALA-D in blood was significantly (P<0·001) increased at days 15 and 30 p.i. δ-ALA-D activity in blood had a significant (P<0·05) negative correlation with haematocrit (r=-0·61) and haemoglobin (r=-0·70) at day 15 p.i. There was a significant (P<0·05) decrease in serum iron and zinc levels and an increase in TBARS levels (P<0·05) during infection. The δ-ALA-D activity in blood was negatively correlated with the levels of iron (r=-0·68) and zinc (r=-0·57) on day 30 p.i. It was concluded that the increased activity of δ-ALA-D in blood might have occurred in response to the anaemia in remission as heme synthesis was enhanced.

Toxicological investigation and antinociceptive property of potassium thiophene-3-trifluoroborate.

The aim of the present study was to evaluate pharmacological and toxicological properties of potassium thiophene-3-trifluoroborate (RBF(3)K). The acute effect of RBF(3)K was evaluated on mice. To this end, mice received a single dose of RBF(3)K (25, 50, and 100 mg/kg, by oral route, p.o.) and after 72 hrs, blood, liver, and kidney samples were collected. delta-Aminolevulinate dehydratase, catalase and glutathione-S-transferase activities, thiobarbituric acid-reactive substances and vitamin C levels, as well as plasma aspartate and alanine aminotransferase activities and creatinine levels were determined. Hepatic and renal lipid peroxidation levels in treated mice did not differ from those in control mice. No significant differences between treated and control mice were detected in hepatic and renal delta-aminolevulinate dehydratase activity. Aspartate and alanine aminotransferase activities as well as urea and creatinine levels were similar among the groups. In contrast, results obtained from in vivo experiments revealed that RBF(3)K, orally administered, reduced peritoneovisceral pain induced by acetic acid administered i.p. Doses of 1, 5, 10, 25, 50, and 100 mg/kg of RBF(3)K were assessed in the antinociceptive investigation and the effect was significantly different than control groups from 5 mg/kg. It was observed that alpha(2-)adrenergic and serotonergic, but not opioidergic, receptors appear to be involved in orally administered RBF(3)K. Mice treated with RBF(3)K did not reveal any motor impairment in the open field. This is a promising compound for more detailed pharmacological studies involving organotrifluoroborate compounds.

Diphenyl Diselenide Decreases Serum Levels of Total Cholesterol and Tissue Oxidative Stress in Cholesterol-fed Rabbits

Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group--regular chow; Cholesterol group--1% cholesterol-enriched diet; diphenyl diselenide group--regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group--the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral delta-aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.

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

Acute Diphenyl Diselenide Treatment Reduces Hyperglycemia But Does Not Change Delta-Aminolevulinate Dehydratase Activity in Alloxan-Induced Diabetes in Rats

This study was designed to evaluate the effect of diphenyl diselenide in a classical model of alloxan-induced diabetes in rats. Oxidative stress is involved in alloxan toxic effects and we have hypothesized that diphenyl diselenide via its antioxidant properties could confer protection against alloxan pancreatic toxicity. Diabetes was induced by administration of alloxan (150 mg/kg, intravenously). Diphenyl diselenide (10 mg/kg, subcutaneously) was administered for 6 d before (prevention group) or for 6 d after (remediation group) diabetes induction. Diphenyl diselenide treatment reduced the blood glucose and fructosamine levels, which were increased in alloxan-treated rats. However, the delta-aminolevulinate dehydratase (delta-ALA-D) activity inhibited by alloxan was not restored by diphenyl diselenide. Moreover, diphenyl diselenide caused by itself an inhibition in hepatic and renal delta-ALA-D activity. Our findings suggest that the acute treatment with diphenyl diselenide reduces the hyperglycemia but does not improve delta-ALA-D activity decreased by alloxan. Although the dose of diphenyl diselenide used here for treating diabetic animals has been relatively high and produced toxic effects, the compound or analogous molecules might not be rejected as a promising anti-hyperglycemic agent.

Experimental Hypothyroidism Inhibits δ-Aminolevulinate Dehydratase Activity in Neonatal Rat Blood and Liver

The aim of this study was to investigate the potential relationship between hypothyroidism and delta-aminolevulinate dehydratase (delta-ALA-D) activity in rat blood and liver. Experimental hypothyroidism was induced in weanling rats by exposing their mothers to propylthiouracil (PTU) diluted in tap water (0.05% w/ v), ad libitum, during the lactational period (PTU group). Control (euthyroid) group included weanling rats whose mothers received just tap water, ad libitum, during the lactational period. Reverted-hypothyroid group (PTU + 3,3',5-triiodo-L-thyronine [T(3)]) included weanling rats whose mothers were exposed to PTU similarly to those in the hypothyroid group, but pups received daily subcutaneous injections of T(3) (20 microg/kg, from Postnatal Days 2-20). After the treatment, serum T(3) levels were drastically decreased (around 70%) in the PTU group, and this phenomenon was almost reverted by exogenous T(3). PTU decreased blood delta-ALA-D activity by 75%, and T(3) treatment prevented such phenomena. Erythrocytes and hemoglobin levels were increased by 10% in PTU-treated animals and higher increments (around 25%) were observed in these parameters when exogenous T(3) was coadministered. Dithiothreitol did not change blood delta-ALA-D activity of PTU-exposed animals when present in the reaction medium, suggesting no involvement of the enzyme's essential thiol groups in PTU-induced delta-ALA-D inhibition. PTU did not affect blood delta-ALA-D activity in vitro. These results are the first to show a correlation between hypothyroidism and decreased delta-ALA-D activity and point to this enzyme as a potential molecule involved with hypothyroidism-related hematological changes.

Effect of Lead Acetate on Cytosolic Thioredoxin Reductase Activity and Oxidative Stress Parameters in Rat Kidneys

Oxidative stress has been suggested to be an important molecular mechanism of toxic effects of lead in the kidney. Thioredoxin reductase-1 is a selenoprotein involved in many cellular redox processes. This study evaluated the effect of acute and chronic exposure intraperitoneally to lead acetate on thioredoxin reductase-1 activity and on other oxidative stress parameters in the rat kidney, as well as on indicators of renal function commonly used to assess lead poisoning. Acute exposure to 25 mg/kg lead acetate increased superoxide dismutase and thioredoxin reductase-1 activity (after 6, 24 and 48 hr), while exposure to 50 mg/kg lead acetate increased catalase activity (after 48 hr) and inhibited delta-aminolevulinate dehydratase activity (after 6, 24 and 48 hr) in the kidney (P < 0.05). Chronic exposure (30 days) to 5 mg/kg lead acetate inhibited delta-aminolevulinate dehydratase and increased glutathione S-transferase, non-protein thiol groups, catalase, thioredoxin reductase-1 and uric acid plasma levels, while exposure to 25 mg/kg lead acetate reduced body weight and delta-aminolevulinate dehydratase, but increased glutathione S-transferase, non-protein thiol groups and uric acid plasma levels (P < 0.05). No changes were observed in thiobarbituric acid reactive substances, glutathione peroxidase, creatinine or inorganic phosphate levels after either acute or chronic exposure. Our results suggest that thioredoxin reductase-1 may be an early indicator of acute exposure to low lead doses.

Comparison of ALAD activities of Citrobacter and Pseudomonas strains and their usage as biomarker for Pb contamination

Delta-aminolevulinate dehydratase (ALAD) activity has been used in prokaryotes and eukaryotes as a biomarker for environmental lead (Pb) exposure and toxicity. Microorganisms are sensitive indicators of toxicity at the fundamental level of ecological organization, but bacterial biomarker studies are focused on the Pseudomonas strains in Group I and E coli. The objectives of the present work were to determine if Burkholderia gladioli belonging to group II, due to its 16SrRNA similarity, can be used as biomarker in metal contamination and compare its possible usage with Pseudomonas aeruginosa and Citrobacter freundii (previously known as Esherichia freundii) and Bacterium freundii which are classified in Group I. In this study, ALAD activity in an environmental strains of Burkholderia gladioli, Pseudomonas aeruginosa, Citrobacter freundii were investigated to evaluate potential inhibition by Pb and other toxic metals. When the ALAD activity of Burkholderia gladioli was tested, Co and Pb decreased activity by 27 and 71%, respectively. In addition to these findings, Zn increased the activity up to 26%. These effects were found to be statistically meaningful (p < 0.05). It was determined that the increase of lead concentration inhibites the ALAD activity at each of the three strains. There was a statistically significant dose-response relationship between ALAD activity in cells of Burkholderia gladioli and Pb (Pearson correlation coefficent = -0.665; r(2) = 0.665, and p < 0.001). The strongest ALAD inhibition which was measured was 90% at Burkholderia gladioli when protein extracts were incubated with 750 muM of Pb. The relationship between Pb and ALAD activity was statistically described by [ALAD Activity] = 0.476-0.000597 x [Pb]. According to the obtained results, we suggest that the ALAD of Burkholderia gladioli can be used as a biomarker for lead contamination in the environment.