scholarly journals Indices of the DNA repair system in the brain of fish as a biomarker of inorganic mercury burden

2021 ◽  
Vol 32 (1) ◽  
pp. 9-16
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
R. O. Novitskyi ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Environmental Pollution ◽  
Dose Range ◽  
Inorganic Mercury ◽  
Mercury Chloride ◽  
Repair System ◽  
Fish Brain ◽  
Low Concentrations ◽  
The Brain

Mercury is a widespread heavy metal that causes a stable and prolonged environmental pollution. Low concentrations of inorganic and organic mercury compounds are found in almost all water bodies. The high level of mercury bioaccumulation is a cause of tissue-specific toxicity, including neurotoxicity. Absorbed in nervous tissue mercury can cause brain disorders both in neural and glial cells. The brain of fish is considered one of the most susceptible targets for cytotoxicity of mercury in aquatic ecosystems. Taking into account that different forms of mercury have widespread distribution and exhibit a strong neurotoxic effect, the assessment of mercury cytotoxicity in the brain of fish is relevant and extremely important. Rainbow trout Oncorhynchus mykiss was exposed to mercury chloride in the dose range of 5-20 μg/L for 60 days to study the chronic exposure of low doses. In this paper, we studied the influence of inorganic mercury on oxidative stress, DNA repair proteins – ERCC1 and PARP1 in the trout’s brain. The results obtained have shown that the chronic effect of inorganic mercury causes dose-dependent oxidative stress in the fish brain. In addition, low concentrations of mercury (10 and 20 μg/L) caused a decrease in the content of ERCC1 in the brain of fish. On the contrary, the same doses have caused an increase in PARP1 expression. That is the chronic influence of low concentrations of inorganic mercury has a negative effect in the fish brain. Observed results showed that inorganic mercury has a potential for suppressing DNA repair and, therefore, increases the instability of genome. Thus, ERCC1 and PARP1 can be considered as the sensitive biomarkers of mercury cytotoxicity in the fish brain. A further study of mercury neurotoxicity is needed to find out the hazard of mercury environmental pollution as well as a validation of biomarkers of their impact.

scholarly journals Astrocyte-Targeted Transporter-Utilizing Derivatives of Ferulic Acid Can Have Multifunctional Effects Ameliorating Inflammation and Oxidative Stress in the Brain

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ahmed Montaser ◽  
Johanna Huttunen ◽  
Sherihan Abdelhamid Ibrahim ◽  
Kristiina M. Huttunen
Keyword(s):  
Oxidative Stress ◽  
Ferulic Acid ◽  
Cellular Uptake ◽  
Parent Drug ◽  
Beneficial Effects ◽  
Multifunctional Compounds ◽  
Low Concentrations ◽  
Amyloid Accumulation ◽  
The Brain ◽  
And Oxidative Stress

Ferulic acid (FA) is a natural phenolic antioxidant, which can exert also several other beneficial effects to combat neuroinflammation and neurodegenerative diseases, such as Alzheimer’s disease. One of these properties is the inhibition of several enzymes and factors, such as β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), cyclooxygenases (COXs), lipoxygenases (LOXs), mammalian (or mechanistic) target for rapamycin (mTOR), and transcription factor NF-κB. We have previously synthesized three L-type amino acid transporter 1- (LAT1-) utilizing FA-derivatives with the aim to develop brain-targeted prodrugs of FA. In the present study, the cellular uptake and bioavailability of these FA-derivatives were evaluated in mouse primary astrocytic cell cultures together with their inhibitory effects towards BACE1, COX/LOX, mTOR, NF-κB, acetylcholinesterase (AChE), and oxidative stress. According to the results, all three FA-derivatives were taken up 200–600 times more effectively at 10 μM concentration into the astrocytes than FA, with one derivative having a high intracellular bioavailability (Kp,uu), particularly at low concentrations. Moreover, all of the derivatives were able to inhibit BACE1, COX/LOX, AChE, and oxidative stress measured as decreased cellular lipid peroxidation. Furthermore, one of the derivatives modified the total mTOR amount. Therefore, these derivatives have the potential to act as multifunctional compounds preventing β-amyloid accumulation as well as combating inflammation and reducing oxidative stress in the brain. Thus, this study shows that converting a parent drug into a transporter-utilizing derivative not only may increase its brain and cellular uptake, and bioavailability but can also broaden the spectrum of pharmacological effects elicited by the derivative.

scholarly journals Mycobacterium bovis BCG recADeletion Mutant Shows Increased Susceptibility to DNA-Damaging Agents but Wild-Type Survival in a Mouse Infection Model

2001 ◽  
Vol 69 (6) ◽  
pp. 3562-3568 ◽  
Author(s):  
Peter Sander ◽  
K. G. Papavinasasundaram ◽  
Thomas Dick ◽  
Evangelos Stavropoulos ◽  
Kerstin Ellrott ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Mycobacterium Bovis ◽  
Defense Mechanisms ◽  
Reactive Oxygen ◽  
Infection Model ◽  
Repair System ◽  
Mouse Infection Model ◽  
Dna Damaging Agents ◽  
Increased Susceptibility

ABSTRACT Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxifies reactive oxygen species, and DNA repair systems, which repair damage resulting from oxidative stress. To (i) determine the relative importance of the DNA repair system when oxidative stress is encountered by theMycobacterium tuberculosis complex during infection of the host and to (ii) provide improved mycobacterial hosts as live carriers to express foreign antigens, the recA locus was inactivated by allelic exchange in Mycobacterium bovisBCG. The recA mutants are sensitive to DNA-damaging agents and show increased susceptibility to metronidazole, the first lead compound active against the dormant M. tuberculosis complex. Surprisingly, the recAgenotype does not affect the in vitro dormancy response, nor does the defect in the DNA repair system lead to attenuation as determined in a mouse infection model. The recA mutants will be a valuable tool for further development of BCG as an antigen delivery system to express foreign antigens and as a source of a genetically stable vaccine against tuberculosis.

scholarly journals Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

2007 ◽  
Vol 98 (6) ◽  
pp. 1116-1119 ◽  
Author(s):  
Jens Lykkesfeldt ◽  
Gilberto Perez Trueba ◽  
Henrik E. Poulsen ◽  
Stephan Christen
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Vitamin C ◽  
Lipid Oxidation ◽  
Protein Oxidation ◽  
Guinea Pigs ◽  
Vitamin C Deficiency ◽  
Markers Of Oxidative Stress ◽  
Selective Preservation ◽  
The Brain

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0·001), tocopherols (P < 0·001) and glutathione (P < 0·001), and a decrease in superoxide dismutase activity (P = 0·005) in the liver, while protein oxidation was significantly increased (P = 0·011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0·001), but in contrast to the liver, ascorbate oxidation (P = 0·034), lipid oxidation (P < 0·001), DNA oxidation (P = 0·13) and DNA incision repair (P = 0·014) were all increased, while protein oxidation decreased (P = 0·003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage by upregulating the DNA repair system

2012 ◽  
Vol 28 (6) ◽  
pp. 421-433 ◽  
Author(s):  
Ki Cheon Kim ◽  
In Kyung Lee ◽  
Kyoung Ah Kang ◽  
Hye Sun Kim ◽  
Sam Sik Kang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Repair System

scholarly journals Toxicity of mercury on the brain: ability of extract of Pistacia atlantica regulated effect

2020 ◽  
Vol 10 (4-s) ◽  
pp. 17-24
Author(s):  
Benahmed Fatiha ◽  
Hayet Fatima Zohra Belhouari ◽  
Radjaa Bounoura ◽  
Elazhari Mehrab ◽  
Omar Kharoubi
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Neuroprotective Effect ◽  
Wistar Rat ◽  
Antioxidant Defense System ◽  
Control Group ◽  
Mercury Chloride ◽  
Male Adult ◽  
Pistacia Atlantica ◽  
The Brain

Objective: The purpose of this study was to evaluate the neuroprotective effect of 150 mg / kg extract of the plant Pistacia atlantica against mercury-induced oxidative stress Methods: Hg was administered intraperitoneally (2,5 mg/kg body weight, one time a week), and P. atlantica and were given orally by gavage at a daily dose (150 mg/kg body weight) to rats for 32 days. 24 male adult Albinos Wistar rats were divided into four groups: group 1 Control, group 2 (HgCl2) group 3 (Hg + P. atlantica) and group 4 (P. atlantica). Paramatrical tests of oxidative stress and histological sections of the cerebral parenchyma. Results: Our results showed that the intraperitoneal injection of mercury chloride HgCl2 causes deleterious effects in the brain resulting in: a failure of redox status by disrupting the antioxidant defense system by a significant decrease in the activity of catalase glutathione peroxidase, glutathione-s-transferase and superoxide dismutase acetylcholinesterase and increase of the activity of the enzyme lactate dehydrogenase. The levels of lipid peroxidation markers were high in TBARS intoxicated rats with protein oxidation increased in the brain intoxicated by. The continuous use of mercury is also at the origin, in brain tissue However, supplementation of P. atlantica extract with mercury-treated rats attenuated some of the harmful and toxic effects of this metal. This clearly demonstrates the protective roles of this plant Keywords: mercury, Pistacia atlantica, Wistar rat, brain, antioxidant, neurotoxicity.

Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries

2008 ◽  
Vol 295 (3) ◽  
pp. H1033-H1043 ◽  
Author(s):  
G. A. Wiggers ◽  
F. M. Peçanha ◽  
A. M. Briones ◽  
J. V. Pérez-Girón ◽  
M. Miguel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Chronic Exposure ◽  
Total Antioxidant Status ◽  
Oxidase Inhibitor ◽  
Mercury Chloride ◽  
Blood Levels ◽  
Resistance Arteries ◽  
Low Concentrations ◽  
Underlying Mechanisms

Increased cardiovascular risk after mercury exposure has been described, but the underlying mechanisms are not well explored. We analyzed the effects of chronic exposure to low mercury concentrations on endothelium-dependent responses in aorta and mesenteric resistance arteries (MRA). Wistar rats were treated with mercury chloride (1st dose 4.6 μg/kg, subsequent dose 0.07 μg·kg−1·day−1im, 30 days) or vehicle. Blood levels at the end of treatment were 7.97 ± 0.59 ng/ml. Mercury treatment: 1) did not affect systolic blood pressure; 2) increased phenylephrine-induced vasoconstriction; 3) reduced acetylcholine-induced vasodilatation; and 4) reduced in aorta and abolished in MRA the increased phenylephrine responses induced by either endothelium removal or the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 μM). Superoxide dismutase (SOD, 150 U/ml) and the NADPH oxidase inhibitor apocynin (0.3 mM) decreased the phenylephrine-induced contraction in aorta more in mercury-treated rats than controls. In MRA, SOD did not affect phenylephrine responses; however, when coincubated with l-NAME, the l-NAME effect on phenylephrine response was restored in mercury-treated rats. Both apocynin and SOD restored the impaired acetylcholine-induced vasodilatation in vessels from treated rats. Endothelial NOS expression did not change in aorta but was increased in MRA from mercury-treated rats. Vascular O2−production, plasmatic malondialdehyde levels, and total antioxidant status increased with the mercury treatment. In conclusion, chronic exposure to low concentrations of mercury promotes endothelial dysfunction as a result of the decreased NO bioavailability induced by increases in oxidative stress. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.

scholarly journals Molecular mechanisms of aluminium ions neurotoxicity in brain cells of fish from various pelagic areas

2017 ◽  
Vol 8 (3) ◽  
pp. 461-466 ◽  
Author(s):  
E. V. Sukharenko ◽  
I. V. Samoylova ◽  
V. S. Nedzvetsky
Keyword(s):  
Oxidative Stress ◽  
Molecular Weight ◽  
Intermediate Filaments ◽  
Aluminum Chloride ◽  
Molecular Mechanisms ◽  
Lepomis Macrochirus ◽  
Fish Brain ◽  
Mature Adult ◽  
Aluminum Ions ◽  
The Brain

Neurotoxic effects of aluminum chloride in higher than usual environment concentration (10 mg/L) were studied in brains of fishes from various pelagic areas, especially in sunfish (Lepomis macrochirus Rafinesque, 1819), roach (Rutilus rutilus Linnaeus, 1758), crucian carp (Carasius carasius Linnaeus, 1758), goby (Neogobius fluviatilis Pallas, 1811). The intensity of oxidative stress and the content of both cytoskeleton protein GFAP and cytosol Ca-binding protein S100β were determined. The differences in oxidative stress data were observed in the liver and brain of fish during 45 days of treatment with aluminum chloride. The data indicated that in the modeling of aluminum intoxication in mature adult fishes the level of oxidative stress was noticeably higher in the brain than in the liver. This index was lower by1.5–2.0 times on average in the liver cells than in the brain. The obtained data evidently demonstrate high sensitivity to aluminum ions in neural tissue cells of fish from various pelagic areas. Chronic intoxication with aluminum ions induced intense astrogliosis in the fish brain. Astrogliosis was determined as result of overexpression of both cytoskeleton and cytosole markers of astrocytes – GFAP and protein S100β (on 75–112% and 67–105% accordingly). Moreover, it was shown that the neurotixic effect of aluminum ions is closely related to metabolism of astroglial intermediate filaments. The results of western blotting showed a considerable increase in the content of the lysis protein products of GFAP with a range of molecular weight from 40–49 kDa. A similar metabolic disturbance was determined for the upregulation protein S100β expression and particularly in the increase in the content of polypeptide fragments of this protein with molecular weight 24–37 kDa. Thus, the obtained results allow one to presume that aluminum ions activate in the fish brain intracellular proteases which have a capacity to destroy the proteins of intermediate filaments. The data presented display the pronounced neurotoxic effect of mobile forms of aluminum on both expression level and the metabolism of molecular markers of astrocytes GFAP and protein S100β. Aluminum ions induce integrated changes, the more important of which are a significant increase in final LPO products, an increase in antioxidant enzyme activity, a reactivation of glial cells in the brain. Integrated determination of the content and polypeptide fragments of specific astrocyte proteins in fishes brains coupled with oxidative stress data may be used as valid biomarkers of toxic pollutant effects in aquatic environments.

Oxidative stress and DNA damage–DNA repair system in vascular smooth muscle cells in artery and vein grafts

2006 ◽  
Vol 1 (1) ◽  
pp. 59-72 ◽  
Author(s):  
S.H. McLaren ◽  
D. Gao ◽  
L. Chen ◽  
R. Lin ◽  
J.R. Eshleman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Repair System ◽  
Vein Grafts

scholarly journals Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Vipin Rawat ◽  
Giulia Bortolussi ◽  
Silvia Gazzin ◽  
Claudio Tiribelli ◽  
Andrés F. Muro
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Strand Break ◽  
Adaptive Responses ◽  
Repair Pathways ◽  
Bilirubin Toxicity ◽  
The Brain

Unconjugated bilirubin is considered a potent antioxidant when present at moderate levels. However, at high concentrations, it produces severe neurological damage and death associated with kernicterus due to oxidative stress and other mechanisms. While it is widely recognized that oxidative stress by different toxic insults results in severe damage to cellular macromolecules, especially to DNA, no data are available either on DNA damage in the brain triggered by hyperbilirubinemia during the neonatal period or on the activation of DNA repair mechanisms. Here, using a mouse model of neonatal hyperbilirubinemia, we demonstrated that DNA damage occurs in vivo in the cerebellum, the brain region most affected by bilirubin toxicity. We studied the mechanisms associated with potential toxic action of bilirubin on DNA in in vitro models, which showed significant increases in DNA damage when neuronal and nonneuronal cells were treated with 140 nM of free bilirubin (Bf), as determined by γH2AX Western blot and immunofluorescence analyses. Cotreatment of cells with N-acetyl-cysteine, a potent oxidative-stress inhibitor, prevented DNA damage by bilirubin, supporting the concept that DNA damage was caused by bilirubin-induced oxidative stress. Bilirubin treatment also activated the main DNA repair pathways through homologous recombination (HR) and nonhomologous end joining (NHEJ), which may be adaptive responses to repair bilirubin-induced DNA damage. Since DNA damage may be another important factor contributing to neuronal death and bilirubin encephalopathy, these results contribute to the understanding of the mechanisms associated with bilirubin toxicity and may be of relevance in neonates affected with severe hyperbilirubinemia.

scholarly journals Chronic Variable Stress Is Responsible for Lipid and DNA Oxidative Disorders and Activation of Oxidative Stress Response Genes in the Brain of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mariola Herbet ◽  
Agnieszka Korga ◽  
Monika Gawrońska-Grzywacz ◽  
Magdalena Izdebska ◽  
Iwona Piątkowska-Chmiel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Indirect Evidence ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Ros Generation ◽  
Repair System ◽  
Stress Response Genes ◽  
Chronic Variable Stress ◽  
The Brain

Chronic environmental stress is associated with reactive oxygen species (ROS) overproduction and the pathogenesis of depression. The purpose of this study was to evaluate biochemical and molecular changes associated with ROS generation in the brains of rats submitted to chronic variable stress. Male Wistar rats (50–55 days old, weighing 200–250 g) were divided in two groups (n=10): control and stressed. Rats in the stressed group were exposed to stress conditions for 40 days. The animals were decapitated and the brain samples were collected. In prefrontal cortex, we measured the following biochemical parameters: lipid peroxidation and concentration of glutathione—GSH, GSSG, GSH/GSSG ratio, glutathione peroxidase, and glutathione reductase activities. In the hippocampus marker of DNA, oxidative damage and expression of DNA-repairing genes (Ogg1,MsrA) and gene-encoding antioxidative transcriptional factor (Nrf2) were determined. The results demonstrate indirect evidence of ROS overproduction and presence of oxidative stress. They also reveal disruption of oxidative defense systems (decreased GR activity, diminished GSH/GSSG ratio, and decreasedNrf2expression) and activation of the oxidative DNA repair system (increasedOgg1andMsrAexpression). Together, the presented data suggest that independent activation of oxidative stress response genes occurs in chronic variable stress conditions.

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