scholarly journals Responsiveness of Lycopersicon pimpinellifolium to acute UV-C exposure: histo-cytochemistry of the injury and DNA damage.

2007 ◽  
Vol 54 (2) ◽  
pp. 273-280 ◽  
Author(s):  
M Iriti ◽  
S Guarnieri ◽  
F Faoro
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Positive Control ◽  
Lycopersicon Pimpinellifolium ◽  
Irradiation Cell ◽  
Leaf Tissues ◽  
In Vitro Effects ◽  
Uv C

The in vivo and in vitro effects of UV-C (254 nm) exposure (0.039 watt . m(-2) . s for 2 h) of currant tomato (Lycopersicon pimpinellifolium), indigenous to Peru and Ecuador, were assayed. H(2)O(2) deposits, dead cells and DNA damage were localized, 12/24 h after irradiation, mainly in periveinal parenchyma of the 1st and 2nd order veins of the leaves, and before the appearance of visible symptoms, which occurred 48 h after irradiation. Cell death index was of 43.5 +/- 12% in exposed leaf tissues, 24 h after treatment. In currant tomato protoplasts, the percentage of viable cells dropped 1 h after UV-C irradiation from 97.42 +/- 2.1% to 43.38 +/- 4.2%. Afterwards, the protoplast viability progressively decreased to 40.16 +/- 7.25% at 2 h, to 38.31 +/- 6.9% at 4 h, and to 36.46 +/- 1.84% at 6 h after the exposure. The genotoxic impact of UV-C radiation on protoplasts was assessed with single cell gel electrophoresis (SCGE, or comet assay). UV-C treatment greatly enhanced DNA migration, with 75.37 +/- 3.7% of DNA in the tail versus 7.88 +/- 5.5% in the case of untreated nuclei. Oxidative stress by H(2)O(2) used as a positive control, induced a similar damage on non-irradiated protoplasts, with 71.59 +/- 5.5% of DNA in the tail, whereas oxidative stress imposed on UV-C irradiated protoplasts slightly increased the DNA damage (85.13 +/- 4.1%). According to these results, SCGE of protoplasts could be an alternative to nuclei extraction directly from leaf tissues.

scholarly journals Arginine-deprivation–induced oxidative damage sterilizes Mycobacterium tuberculosis

2018 ◽  
Vol 115 (39) ◽  
pp. 9779-9784 ◽  
Author(s):  
Sangeeta Tiwari ◽  
Andries J. van Tonder ◽  
Catherine Vilchèze ◽  
Vitor Mendes ◽  
Sherine E. Thomas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Mycobacterium Tuberculosis ◽  
De Novo ◽  
Target Space ◽  
Biosynthesis Pathway ◽  
Arginine Biosynthesis ◽  
Arginine Deprivation

Reactive oxygen species (ROS)-mediated oxidative stress and DNA damage have recently been recognized as contributing to the efficacy of most bactericidal antibiotics, irrespective of their primary macromolecular targets. Inhibitors of targets involved in both combating oxidative stress as well as being required for in vivo survival may exhibit powerful synergistic action. This study demonstrates that the de novo arginine biosynthetic pathway in Mycobacterium tuberculosis (Mtb) is up-regulated in the early response to the oxidative stress-elevating agent isoniazid or vitamin C. Arginine deprivation rapidly sterilizes the Mtb de novo arginine biosynthesis pathway mutants ΔargB and ΔargF without the emergence of suppressor mutants in vitro as well as in vivo. Transcriptomic and flow cytometry studies of arginine-deprived Mtb have indicated accumulation of ROS and extensive DNA damage. Metabolomics studies following arginine deprivation have revealed that these cells experienced depletion of antioxidant thiols and accumulation of the upstream metabolite substrate of ArgB or ArgF enzymes. ΔargB and ΔargF were unable to scavenge host arginine and were quickly cleared from both immunocompetent and immunocompromised mice. In summary, our investigation revealed in vivo essentiality of the de novo arginine biosynthesis pathway for Mtb and a promising drug target space for combating tuberculosis.

scholarly journals The Rational Design and Biological Mechanisms of Nanoradiosensitizers

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 504 ◽  
Author(s):  
Hainan Sun ◽  
Xiaoling Wang ◽  
Shumei Zhai
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Damage ◽  
Rational Design ◽  
Design Strategies ◽  
Biological Mechanisms ◽  
Normal Tissues ◽  
Current State

Radiotherapy (RT) has been widely used for cancer treatment. However, the intrinsic drawbacks of RT, such as radiotoxicity in normal tissues and tumor radioresistance, promoted the development of radiosensitizers. To date, various kinds of nanoparticles have been found to act as radiosensitizers in cancer radiotherapy. This review focuses on the current state of nanoradiosensitizers, especially the related biological mechanisms, and the key design strategies for generating nanoradiosensitizers. The regulation of oxidative stress, DNA damage, the cell cycle, autophagy and apoptosis by nanoradiosensitizers in vitro and in vivo is highlighted, which may guide the rational design of therapeutics for tumor radiosensitization.

DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in blood and brain of rats subjected to a model of hyperphenylalaninemia

2013 ◽  
Vol 91 (5) ◽  
pp. 319-324 ◽  
Author(s):  
Kellen R. Simon ◽  
Rosane M. dos Santos ◽  
Giselli Scaini ◽  
Daniela D. Leffa ◽  
Adriani P. Damiani ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cerebral Cortex ◽  
Phenylalanine Hydroxylase ◽  
Neurological Dysfunction ◽  
Control Group ◽  
Acute Administration ◽  
Dna Migration ◽  
In Vitro Effects

Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering that high levels of Phe are associated with neurological dysfunction and that the mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main objective of this study was to investigate the in vivo and in vitro effects of Phe on DNA damage, as determined by the alkaline comet assay. The results showed that, compared to control group, the levels of DNA migration were significantly greater after acute administration of Phe, p-chlorophenylalanine (p-Cl-Phe, an inhibitor of PAH), or a combination thereof in cerebral cortex and blood, indicating DNA damage. These treatments also provoked increase of carbonyl content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium, we observed an increase in the frequency and index of DNA damage in the cerebral cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex and blood of rats receiving Phe, suggesting that this mechanism could be, at least in part, responsible for the neurological dysfunction in PKU patients.

scholarly journals DDB2, an Essential Mediator of Premature Senescence

2010 ◽  
Vol 30 (11) ◽  
pp. 2681-2692 ◽  
Author(s):  
Nilotpal Roy ◽  
Tanya Stoyanova ◽  
Carmen Dominguez-Brauer ◽  
Hyun Jung Park ◽  
Srilata Bagchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Excision Repair ◽  
Culture Shock ◽  
Premature Senescence ◽  
Antioxidant Genes ◽  
Repair Protein ◽  
High Level

ABSTRACT Reactive oxygen species (ROS) is critical for premature senescence, a process significant in tumor suppression and cancer therapy. Here, we reveal a novel function of the nucleotide excision repair protein DDB2 in the accumulation of ROS in a manner that is essential for premature senescence. DDB2-deficient cells fail to undergo premature senescence induced by culture shock, exogenous oxidative stress, oncogenic stress, or DNA damage. These cells do not accumulate ROS following DNA damage. The lack of ROS accumulation in DDB2 deficiency results from high-level expression of the antioxidant genes in vitro and in vivo. DDB2 represses antioxidant genes by recruiting Cul4A and Suv39h and by increasing histone-H3K9 trimethylation. Moreover, expression of DDB2 also is induced by ROS. Together, our results show that, upon oxidative stress, DDB2 functions in a positive feedback loop by repressing the antioxidant genes to cause persistent accumulation of ROS and induce premature senescence.

scholarly journals Dual Roles of Helicobacter pylori NapA in Inducing and Combating Oxidative Stress

2006 ◽  
Vol 74 (12) ◽  
pp. 6839-6846 ◽  
Author(s):  
Ge Wang ◽  
Yang Hong ◽  
Adriana Olczak ◽  
Susan E. Maier ◽  
Robert J. Maier
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Wild Type Mouse ◽  
Wild Type ◽  
Oxygen Intermediates ◽  
Physiological Analysis ◽  
H Pylori

ABSTRACT Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

scholarly journals Targeting Oxidative Stress with Antioxidant Duotherapy After Experimental Traumatic Brain Injury

2021 ◽  
Vol 22 (19) ◽  
pp. 10555
Author(s):  
Jenni Kyyriäinen ◽  
Natallie Kajevu ◽  
Ivette Bañuelos ◽  
Leonardo Lara ◽  
Anssi Lipponen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Positive Control ◽  
Cortical Lesion ◽  
Favorable Effect ◽  
Neuronal Viability ◽  
Severe Tbi ◽  
Improved Performance ◽  
In Vivo Effects

We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug N-acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and validated the results in a lateral fluid-percussion model of TBI in rats. As in vitro measures, we assessed neuronal viability by microtubule-associated-protein 2 immunostaining, neuroinflammation by monitoring tumor necrosis factor (TNF) levels, and neurotoxicity by measuring nitrite levels. In vitro, duotherapy with NAC and SFN reduced nitrite levels to 40% (p < 0.001) and neuroinflammation to –29% (p < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (p < 0.001). The effect of NAC was negligible, however, compared with SFN. In vivo, antioxidant duotherapy slightly improved performance in the beam walking test. Interestingly, duotherapy treatment decreased the plasma interleukin-6 and TNF levels in sham-operated controls (p < 0.05). After TBI, no treatment effect on HMGB1 or plasma cytokine levels was detected. Also, no treatment effects on the composite neuroscore or cortical lesion area were detected. The robust favorable effect of duotherapy on neuroprotection, neuroinflammation, and oxidative stress in neuron-BV2 microglial co-cultures translated to modest favorable in vivo effects in a severe TBI model.

Bisphenol A analogues bisphenol B, bisphenol F, and bisphenol S induce oxidative stress, disrupt daily sperm production, and damage DNA in rat spermatozoa: a comparative in vitro and in vivo study

2019 ◽  
Vol 35 (4) ◽  
pp. 294-303 ◽  
Author(s):  
Asad Ullah ◽  
Madeeha Pirzada ◽  
Sarwat Jahan ◽  
Hizb Ullah ◽  
Muhammad Jamil Khan
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Bisphenol A ◽  
Estrogenic Activity ◽  
Bisphenol S ◽  
Endocrine Disrupting Chemical ◽  
Sperm Dna Damage ◽  
Bisphenol F

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report the mechanisms by which BPA and three of its analogues bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) cause generation of reactive oxygen species (ROS), sperm DNA damage, and oxidative stress in both in vivo and in vitro rat models. Sperm were incubated with different concentrations (1, 10, and 100 µg/L) of BPA and its analogues BPB, BPF, and BPS for 2 h. BPA and its analogues were observed to increase DNA fragmentation, formation of ROS, and affected levels of superoxide dismutase at higher concentration groups. In an in vivo experiment, rats were exposed to different concentrations (5, 25, and 50 mg/kg/day) of BPA, BPB, BPF, and BPS for 28 days. In the higher dose (50 mg/kg/day) treated groups of BPA and its analogues BPB, BPF, and BPS, DNA damage was observed while the motility of sperm was not affected.

CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo through oxidative stress-induced DNA damage and cell apoptosis

2017 ◽  
Vol 79 (6) ◽  
pp. 1129-1140 ◽  
Author(s):  
Yen-Yun Wang ◽  
Yuk-Kwan Chen ◽  
Stephen Chu-Sung Hu ◽  
Ya-Ling Hsu ◽  
Chun-Hao Tsai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cells

Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats

2016 ◽  
Vol 38 (2) ◽  
pp. 150-162 ◽  
Author(s):  
Bhupesh Patel ◽  
Saroj Kumar Das ◽  
Manorama Patri
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Brain Development ◽  
Early Adolescence ◽  
Hippocampal Neurons ◽  
Oxidative Dna Damage ◽  
Specific Effect ◽  
Adolescence Period

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 µg/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2′-deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 μg/kg, when compared to naïve and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats.

Sign in / Sign up

Export Citation Format

Share Document