Δ-aminolevulinic Dehydratase Research Articles

Oxidative profile, inflammatory responses and δ-aminolevulinate dehydratase enzyme activity in influenza B virus infection.

determine the activity of the delta-aminolevulinate dehydratase (δ-ALA-D) enzyme, oxidative stress biomarkers and the expression of cytokines in those infected with influenza B virus (IBV). to evaluate the activity of the δ-ALA-D enzyme, lipid peroxidation estimated as levels of thiobarbituric acid reactive substances (TBARS), protein (PSH), non-protein (NPSH) thiol groups, ferric reducing antioxidant power (FRAP), vitamin C concentration (VIT C) and cytokine levels in IBV infected individuals (n = 50) and a control group (n = 30). δ-ALA-D activity was significantly lower in IBV-infected compared to controls, as well as levels of thiols, vitamin C and FRAP. Lipid peroxidation and cytokine levels IL-6, IL-10, IL-17A and IFN-y were statistically higher in the IBV group. we found evidenced of the generation of oxidants, the depletion of the antioxidant system, the decrease in the activity of the δ-ALA-D enzyme and the increase in the synthesis of cytokines, thus contributing to a better understanding of oxidative and inflammatory pathways during IBV infection.

Attenuating the toxicity of isoproturon to maize by priming in ascorbate, glutathione or thiourea

Maize grains were primed in ascorbate (AsA), glutathione (GSH) or thiourea (TU) for 24 h, sown in pots for 10 days and then treated with Ipu whose residues persisted in shoots from the next day and increased over 8 days and then decreased continuously. The herbicide significantly reduced growth parameters, pigments, photosynthetic activity parameters, AsA, GSH and GSH/oxidized glutathione (GSSG) ratio and inhibited the activities of δ-aminolevulinate dehydratase (ALA-D), ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), phosphoenolpyruvate carboxylase (PEP-C), malate dehydrogenase (MDH), pyruvate phosphate dikinase (PPDK), superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) but significantly increased malondialdehyde (MDA), H 2 O 2 , superoxide radicals (O 2 ∙−) and GSSG. The priming mostly improved the tested parameters and overcame the deficiency in enzymatic and non-enzymatic antioxidants as well as in the photosynthetic parameters and enzyme activities; AsA or GSH were more efficient than TU. Besides, in vitro tests showed that the inhibition constant (IC50) for Ipu was lowest for CAT but highest for PPDK indicating that CAT was the most inhibited but PPDK was the least while the others were moderate. Furthermore, calculations showed that Ipu competitively inhibited ALA-D, Rubisco, APX, PEP-C, MDH and PPDK but caused non-competitive inhibition of APX, CAT and SOD. These findings reveal that maize was prone to suffering from Ipu; however, priming attenuated the toxicity of Ipu and overcame the herbicide impacts by repairing, maintaining and improving antioxidants and photosynthetic activities .

Effect of a purine derivative containing selenium to improve memory decline and anxiety through modulation of the cholinergic system and Na+/K+-ATPase in an Alzheimer's disease model.

Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that can stop this disease. To investigate the binding affinity of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) with acetylcholinesterase (AChE), to verify the effects of FSP in an AD model in mice and to evaluate the toxicological potential of this compound in mice. The binding affinity of FSP with AChE was investigated by molecular docking analyses. The AD model was induced by streptozotocin (STZ) in Swiss mice after FSP treatment (1mg/kg, intragastrically (i.g.)), 1st-10th day of the experimental protocol. Anxiety was evaluated in an elevated plus maze test, and memory impairment was evaluated in the Y-maze, object recognition and step-down inhibitory avoidance tasks. The cholinergic system was investigated based on by looking at expression and activity of AChE and expression of choline acetyltransferase (ChAT). We evaluated expression and activity of Na+/K+-ATPase. For toxicological analysis, animals received FSP (300mg/kg, i.g.) and aspartate aminotransferase, alanine aminotransferase activities were determined in plasma and δ-aminolevulinate dehydratase activity in brain and liver. FSP interacts with residues of the AChE active site. FSP mitigated the induction of anxiety and memory impairment caused by STZ. FSP protected cholinergic system dysfunction and reduction of activity and expression of Na+/K+-ATPase. FSP did not modify toxicological parameters evaluated and did not cause the death of mice. FSP protected against anxiety, learning and memory impairment with involvement of the cholinergic system and Na+/K+-ATPase in these actions.

Influence of VDR and HFE polymorphisms on blood lead levels of occupationally exposed workers.

Lead is a ubiquitous heavy metal toxin of significant public health concern. Every individual varies in their response to lead's toxic effects due to underlying genetic variations in lead metabolizing enzymes or proteins distributed in the population. Earlier studies, including our lab, have attributed the influence of ALAD (δ-Aminolevulinate dehydratase) polymorphism on blood lead retention and ALAD activity. The present study aimed to investigate the influence of VDR (Vitamin D receptor) and HFE (Hemochromatosis) polymorphisms in modulating blood lead levels (BLLs) of occupationally exposed workers. 164 lead-exposed subjects involved in lead alloy manufacturing and battery breaking and recycling processes and 160 unexposed controls with BLLs below 10 µg/dL recruited in the study. Blood lead levels, along with a battery of biochemical assays and genotyping, were performed. Regression analysis revealed a negative influence of BLLs on ALAD activity (p < 0.0001) and a positive influence on smokeless tobacco use (p < 0.001) in lead-exposed subjects. A predicted haplotype of the three VDR polymorphisms computed from genotyping data revealed that T-A-A haplotype increased the BLLs by 0.93 units (p ≤ 0.05) and C-C-A haplotype decreased the BLLs by 7.25 units (p ≤ 0.05). Further analysis revealed that the wild-type CC genotype of HFE H63D presented a higher median BLL, indicating that variant C allele may have a role in increasing the concentration of lead. Hence, the polymorphism of genes associated with lead metabolism might aid in predicting genetic predisposition to lead and its associated effects.

Lead exposure induces metabolic reprogramming in rat models

Lead is a toxin of great public health concern affecting the young and aging population. Several factors such as age, gender, lifestyle, dose, and genetic makeup result in interindividual variations to lead toxicity mainly due to variations in metabolic consequences. Hence, the present study aimed to examine dose-dependent lead-induced systemic changes in metabolism using rat model by administering specific doses of lead such as 10 (low lead; L-Pb), 50 (moderate lead; M-Pb), and 100 mg/kg (high lead; H-Pb) body weight for a period of one month. Biochemical and haematological analysis revealed that H-Pb was associated with low body weight and feed efficiency, low total protein levels (p ≤ 0.05), high blood lead (Pb-B) levels (p ≤ 0.001), low ALAD (δ-aminolevulinate dehydratase) activity (p ≤ 0.0001), high creatinine (p ≤ 0.0001) and blood urea nitrogen (BUN) (p ≤ 0.01) levels, elevated RBC and WBC counts, reduced haemoglobin and blood cell indices compared to control. Spatial learning and memory test revealed that H-Pb exposed animals presented high latency to the target quadrant and escape platform compared to other groups indicating H-Pb alters cognition function in rats. Histopathological changes were observed in liver and kidney as they are the main target organs of lead toxicity. LC-MS analysis further revealed that Butyryl-L-carnitine (p ≤ 0.01) and Ganglioside GD2 (d18:0/20:0) (p ≤ 0.05) levels were significantly reduced in H-Pb group compared to all groups. Further, pathway enrichment analysis revealed abundance and significantly modulated metabolites associated with oxidative stress pathways. The present study is the first in vivo model of dose-dependent lead exposure for serum metabolite profiling.

Interferon gamma/interleukin-4 modulation, anti-inflammatory and antioxidant effects of hesperidin in complete Freund’s adjuvant (CFA)-induced arthritis model of rats

Background This study sought to assess the effect of hesperidin on serum inflammatory cytokines and oxidative damage in liver of complete Freund’s adjuvant (CFA)-induced arthritic rats. Method Fifty-six adult female Wistar rats (220–250 g) were acclimatized for two weeks. Intraplantar injection of CFA was done for the induction of arthritis and confirmed on the 14th day prior to oral administration of 40 and 80 mg/kg of hesperidin or dexamethasone for 45 days. Result The result showed that treatment with both doses of hesperidin and dexamethasone in the joint of arthritic rats significantly (p < .05) diminished paw swelling/edema and arthritis score as well as enhanced latency in thermal hyperalgesia test. In addition, hesperidin treatment in arthritis rats showed significant (p < .01) improvement in red blood cells and platelets counts as well as hemoglobin and hematocrit compared to the arthritis control rat group. Furthermore, hesperidin treatment significantly (p < .05) reduced serum interferon gamma (IFN-γ) and interleukin-4 (IL-4) levels in arthritic rat. In addition, treatment with hesperidin significantly (p < .05) decreased the liver of thiobarbituric acid reactive species and reactive oxygen species levels but raised the levels of total and non-protein thiols of rat induced with CFA. The reduced activities of liver δ-aminolevulinate dehydratase, catalase, glutathione-S transferase in arthritic rats were significantly (p < .05) increased with hesperidin treatment in arthritic rats. This study suggests that hesperidin demonstrated an anti-arthritic effect via modulation of serum IFN-γ and IL-4 levels as well as protection against oxidative damage. Conclusion Hence, hesperidin could be a potential immune-modulatory, anti-inflammatory and anti-oxidant agent.

Role of 7-chloro-4-(phenylselanyl) quinoline in the treatment of oxaliplatin-induced hepatic toxicity in mice.

There is an increasing incidence of hepatotoxicity induced by oxaliplatin (OXA); therefore, researchers' attention has been drawn to therapeutic alternatives that may decrease OXA-induced hepatotoxicity. Studies indicate that oxidative stress plays a major role in OXA-induced liver injury. As several pharmacological effects of 7-chloro-4-(phenylselanyl) quinole (4-PSQ) involve its antioxidant action, the hypothesis that this organoselenium compound could be promising for the treatment or prevention of hepatotoxicity induced by treatment with OXA was investigated. To test this hypothesis, male Swiss mice received OXA (10 mg·kg-1) on days 0 and 2, followed by oral administration of 4-PSQ (1 mg·kg-1) on days 2 to 14. 4-PSQ reduced the plasma aspartate, and alanine aminotransferase activity increased by exposure to OXA. The histopathological examination of the liver showed that 4-PSQ markedly improved OXA-induced hepatic injury. In addition, treatment with 4-PSQ reduced the oxidation of lipids and proteins (thiobarbituric acid reactive species levels and protein carbonyl content) and attenuated the increase of hepatic catalase and glutathione peroxidase activity caused by OXA. The inhibition of hepatic δ-aminolevulinic dehydratase activity induced by OXA was reverted by 4-PSQ. In conclusion, results indicate that 4-PSQ may be a good therapeutic strategy for attenuating OXA-induced liver damage.

Role of 7-chloro-4-(phenylselanyl) quinoline as an anti-aging drug fighting oxidative damage in different tissues of aged rats.

This study investigated whether subacute treatment with 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) presented antioxidant action in oxidative stress associated with aging in different rat tissues. We also investigated whether plasma selenium levels were altered by aging, as well as the contribution of 4-PSQ administration to these levels. Aged Wistar male rats (23month old) were intragastrically treated with 4-PSQ (5mg/kg) for seven days. On the 14th day of the experimental protocol, plasma was collected to determine selenium levels and biochemical markers of renal and hepatic damage. Furthermore, liver, kidney, spleen and cerebral cortex were removed to determine thiobarbituric acid reactive species (TBARS), non-protein thiols (NPSH), glutathione S-transferase (GST), catalase (CAT) and δ-aminolevulinate dehydratase (ALA-D). Our results showed that one or more parameters changed markedly in the liver, kidney, spleen and cerebral cortex of aged rats. Moreover, biochemical markers of renal and hepatic damage and selenium levels are changed in the plasma of aged rats. Treatment with 4-PSQ repaired redox homeostasis in tissues of aged rats, as well as plasma biochemical markers of renal and hepatic damage and selenium levels. In conclusion, 4-PSQ presented an antioxidant effect in tissues of aged rats, restoring selenium levels, and contributing to the restoration of the damage caused by aging. Thus, 4-PSQ could be a potential candidate for the management of age-related oxidative damage, acting as an anti-aging drug.

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.

Effect of Zinc on the Oxidative Stress Biomarkers in the Brain of Nickel-Treated Mice.

The overexposure to nickel due to the extensive use of it in modern technology remains a major public health concern. The mechanisms of pathological effects of this metal remain elusive. The present study was devoted to evaluate the effect of nickel on the oxidative state of the brain cells of mice and to assess whether zinc as redox state modulator could efficiently protect cells against nickel's neurotoxicity. As oxidative stress biomarkers in the present study, we have measured the concentrations of reduced glutathione, metallothioneins, and malondialdehyde and the activity of the enzyme δ-aminolevulinate dehydratase. For the single metal exposure, mice were i.p. injected once with solutions of NiCl2 and/or ZnSO4; repeated exposure was performed i.p. injecting metal salt solutions for 14 days (once a day). The control mice received i.p. injections of saline. Results of our study demonstrate that single and 14 days of Ni2+ exposure decreased reduced glutathione and increased malondialdehyde contents in the brain of mice. Repeated Ni2+ administration significantly inhibited δ-aminolevulinate dehydratase while increasing brain metallothionein concentration at both exposure periods. Zinc exhibited a protective effect against nickel-induced glutathione and lipid peroxidation in brain cells of mice at both intervals of time, while repeated exposure to this metal significantly raised the brain metallothionein content. Repeated Zn2+ pretreatment protected δ-aminolevulinate dehydratase from Ni2+-induced inhibition and significantly increased metallothionein concentration at both investigated time intervals.

Post-mortem interval estimative through determination of catalase and Δ-aminolevulinate dehydratase activities in hepatic, renal, skeletal muscle and cerebral tissues of Swiss mice

Purpose: Determining the post-mortem interval (PMI) is one of the challenging tasks in forensic science due to the lack of quick and inexpensive methods. Our objective is to develop innovative and alternative means for PMI evaluation.Methods: The relationship between PMI and enzymatic modifications in mice tissues was described. After being sacrificed, Swiss mice were randomly divided into groups according to the time elapsed since death. The activities of catalase (CAT) and δ-aminolevulinate dehydratase (δ-ALA-D) were determined in hepatic, renal, skeletal muscle and cerebral tissues.Results: CAT activity increased in kidney and brain 6 h after death and this increase remained for up to 24 h in the brain and 48 h in the kidney. δ-ALA-D had its activity decreased in the liver and kidneys in 6 h. In the skeletal muscle, δ-ALA-D activity was reduced only 48 h after death. Conversely, an increase on δ-ALA-D activity was observed in the brain at 6 h, followed by its decrease at 24 and 48 h.Conclusion: With the association of this set of results, it is possible to provide an estimate of PMI. Additionally, these results can be used as an auxiliary parameter associated with other methods to estimate PMI.

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.

Evaluation of hematological, biochemical parameters and thiol enzyme activity in chrome plating workers.

The most commonly used solution in chrome plating bath is chromic acid (hexavalent Cr), and a considerable amount of mists is released into the air and consequently produce hazards to workers. Thus, the aim of this study was to evaluate whether the biomarker of exposure to metals, specially Cr levels, presents associations with hematological and biochemical parameters and if they can alter the activity of enzymes that contain thiol groups such as pyruvate kinase, creatine kinase, adenylate kinase, and δ-aminolevulinate dehydratase. Fifty male chrome plating workers were used for exposed group and 50 male non-exposed workers for control group. For that, biological monitoring was performed through quantification of metals on total blood and urine by inductively coupled plasma mass spectrometry (ICP-MS) and enzyme activity was performed by spectrometry in erythrocytes. In addition, chromium levels in water was quantified and ecotoxicology assay was performed with Allium cepa test. The results demonstrated that blood and urinary chromium levels in exposed group were higher than the control group (p < 0.0001). Furthermore, decreased activity of enzymes was found in those that contain thiol groups from exposed group when compared with the control group (p < 0.001). The water analysis did not present a statistical difference between control and exposed groups (p > 0.05), demonstrating that water did not seem to be the source of contamination. In summary, our findings indicated some toxicology effects observed in the exposed group, such as thiol enzyme inhibition, mainly associated with occupational exposure in chrome plating and besides the presence of other metals, and Cr demonstrated to influence the activity of the enzymes analyzed in this research.

Neuroprotective effects of berberine on recognition memory impairment, oxidative stress, and damage to the purinergic system in rats submitted to intracerebroventricular injection of streptozotocin.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer's type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3mg/kg or saline, and 3days later, were started on a treatment of BRB or saline for 21days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (EC-5'-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.

Interaction of metals from group 10 (Ni, Pd, and Pt) and 11 (Cu, Ag, and Au) with human blood δ-ALA-D: in vitro and in silico studies.

Mammalian δ-aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for catalytic activity, and is an important molecular target for the widespread environmental toxic metals. The δ-ALA-D inhibition mechanism by metals of Group 10 (Ni, Pd, and Pt) and 11 (Cu, Ag, and Au) of the periodic table has not yet been determined. The objective of this study was to characterize the molecular mechanism of δ-ALA-D inhibition caused by the elements of groups 10 and 11 using in vitro (δ-ALA-D activity from human erythrocytes) and in silico (docking simulations) methods. Our results showed that Ni(II) and Pd(II) caused a small inhibition (~ 10%) of the δ-ALA-D. Pt(II) and Pt(IV) significantly inhibited the enzyme (75% and 44%, respectively), but this inhibition was attenuated by Zn(II) and dithiothreitol (DTT). In group 11, all metals inhibited δ-ALA-D with great potency (~ 70-90%). In the presence of Zn(II) and DTT, the enzyme activity was restored to the control levels. The in silico molecular docking data suggest that the coordination of the ions Pt(II), Pt(IV), Cu(II), Ag(I), and Au(III) with thiolates groups from C135 and C143 residues from the δ-ALA-D active site are crucial to the enzyme inhibition. The results indicate that a possible mechanism of inhibition of δ-ALA-D by these metals may involve the replacement of the Zn(II) from the active site and/or the cysteinyl residue oxidation.

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.

Influence of gestational diabetes on the activity of δ-aminolevulinate dehydratase and oxidative stress biomarkers

ABSTRACTObjective: This study aimed to evaluate the activity of delta-aminolevulinate dehydratase (δ-ALA-D) and oxidative stress biomarkers in pregnant women with gestational diabetes mellitus (GDM), in order to demonstrate the involvement of oxidative stress in this condition, which presents pathophysiology still undetermined.Methods: δ-ALA-D activity, lipid peroxidation estimated as the levels of thiobarbituric acid reactive substances (TBARS), protein (P-SH) and non-protein thiol (NP-SH) content, catalase (CAT) activity and concentration of vitamin C (VIT C) in samples of pregnant women with GDM (n = 48) and in healthy pregnant women (n = 30), who constituted the control group.Results: The δ-ALA-D activity was significantly lower in pregnant women with GDM compared to controls, as well as levels of thiols, VIT C and CAT activity. Lipid peroxidation was higher in GDM group.Discussion: The results suggest that the main factor for the increase in oxidative stress and reduced δ-ALA-D activity in diabetic pregnant women is gestational hyperglycemic environment, which changed the redox balance and interfered on mechanism of the δ-ALA-D activity in relation to normoglycemic pregnant women.

The effect of simulated microgravity on formation of the pigment apparatus in etiolated barley seedlings

The effect of horizontal clinorotation on the dynamics of the accumulation of the main photosynthetic pigments in the greening of 6-day-old etiolated barley seedlings has been studied. The content of protochlorophillide, the direct precursor of chlorophyll a, in clinorotated seedlings in the dark was 9–20% lower than in the control group. After exposure of barley seedlings to light for 12 h under clinorotation, chlorophyll accumulation lagged behind the control by 45% and reached the control value after 48–72 h. The total content of carotenoids increased many fold during greening; at the first stage the carotenoid level in clinorotated seedlings was less than in the control. The synthesis rates of δ-aminolevulinic acid and δ-aminolevulinate dehydratase activity in clinorotated seedlings were slower than in the control after 24 h of greening and after 72 h of greening reaching the control values. The activity of Mg-protoporphyrin IX chelatase catalyzing the incorporation of Mg ions in the structure of chlorophyll a, did not change when exposed to clinorotation. The results we obtained show inhibition of the initial stages of chlorophyll biosynthesis in the conditions of simulated microgravity. The light, to a certain extent, decreases the negative effect of microgravity on the formation of the photosynthetic apparatus in plants.

Antioxidant compound (E)-2-benzylidene-4-phenyl-1,3-diselenole protects rats against thioacetamide-induced acute hepatotoxicity.

The aim of this study was to investigate whether (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD) protects against hepatotoxicity induced by thioacetamide (TAA). On the first day of treatment, male adult Wistar rats received BPD (10 or 50 mg·kg-1). On the second day, the rats received a single intraperitoneal injection of TAA (400 mg·kg-1). Twenty-four hours after TAA administration, biochemical determinations and liver histological analysis were carried out. BPD (50 mg·kg-1) reduced plasma aspartate and alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities increased by TAA exposure. Treatment with BPD was effective against increased lipid peroxidation levels and attenuated a decrease in hepatic reduced glutathione and ascorbic acid levels as well as an inhibition of glutathione peroxidase activity caused by TAA exposure. The higher dose of BPD protected against the inhibition of hepatic δ-aminolevulinic dehydratase activity induced by TAA. Finally, histopathological examination of the liver showed that BPD markedly ameliorated TAA-induced hepatic injury. In conclusion, BPD protected against hepatotoxicity and oxidative stress caused by TAA exposure in rats.

Antidepressant-like effect of a new selenium-containing compound is accompanied by a reduction of neuroinflammation and oxidative stress in lipopolysaccharide-challenged mice.

Organoselenium compounds and indoles have gained attention due to their wide range of pharmacological properties. Depression is a recurrent and disabling psychiatric illness and current evidences support that oxidative stress and neuroinflammation are mechanisms underlying the pathophysiology of this psychiatric condition. Here, we evaluated the effect of 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI) in lipopolysaccharide (LPS)-induced depressive-like behaviour, neuroinflammation and oxidative stress in male mice. CMI pre-treatment (20 and 50 mg/kg, intragastrically) significantly attenuated LPS (0.83 mg/kg, intraperitoneally)-induced depressive-like behaviour in mice by reducing the immobility time in the tail suspension test (TST) and forced swimming test (FST). CMI pre-treatment ameliorated LPS-induced neuroinflammation by reducing the levels of interleukin (IL)-1β, IL-4 and IL-6 in the hippocampus and prefrontal cortex, as well as markers of oxidative damage. Additionally, we investigated the toxicological effects of CMI (200 mg/kg, i.g.) in the liver, kidney and brain through determination of the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), δ-aminolevulinate dehydratase (δ-ALA-D) and creatinine levels. These biomarkers were not modified, indicating the possible absence of neuro-, hepato- and nephrotoxic effects. Our results suggest that CMI could be a therapeutic approach for the treatment of depression and other neuropsychiatric disorders associated with inflammation and oxidative stress.