Developing a hybrid mesoscale model to predict the impact of oxidative stress damage to individual microtubules on overall cytoskeletal mechanics

Author(s):  
H. Zhao ◽  
B. Sokhansanj
2020 ◽  
Vol 10 (5) ◽  
pp. 578-586
Author(s):  
Areeg M. Abdelrazek ◽  
Shimaa A. Haredy

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.


2021 ◽  
Author(s):  
Shi-Wei Li ◽  
Ming-Hui Chang ◽  
Wen-Jun Zhao ◽  
He-Lian Li ◽  
Hong-Jie Sun ◽  
...  

Abstract 2,6-dichlorobenzoquinone (2,6-DCBQ) is an emerging disinfection byproduct frequently detected in drinking water. Previous studies have indicated that 2,6-DCBQ causes oxidative stress damage in some live systems, but this has yet to be tested in vivo in mammals. In the present study, adult mice were exposed to 2,6-DCBQ for 30 d via gavage at 0 ~ 100 mg kg− 1 with the responses of antioxidant enzymes (superoxide dismutase [SOD] and catalase [CAT]), key oxidative stress response genes (Heme oxygenase-1 [HO-1], NADPH quinone oxidoreductase 1 [NQO1] and glutamate-L-cysteine ligase catalytic subunit [GCLC]) in the Nrf2-keap1 pathway, and lipid peroxidation (malonaldehyde, MDA) as an indicator of oxidative damage being measured. Our results indicated that 2,6-DCBQ decreased the activities of SOD and CAT, repressed transcription of key genes in the Nrf2-keap1 pathway, and caused measurable oxidative damage. These results reveal the impact of 2,6-DCBQ in a model mammalian system and are key to understanding the potential impacts of 2,6-DCBQ in humans.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0259100
Author(s):  
Siyi Zhao ◽  
Yanqiao Zhu ◽  
Wenwen Liu ◽  
Xiaoshan Wang ◽  
Han Wang ◽  
...  

Excess copper (Cu) in soil due to industrial and agricultural practices can result in reduced plant growth. Excess Cu resulted in severely retarded root growth with severe discoloration of Alfalfa (Medicago sativa) and Medicago truncatula. Growth in the presence of hydrogen peroxide resulted in similar symptoms that could be partially recovered by the addition of the reductant ascorbic acid revealing damage was likely due to oxidative stress. The addition of proanthocyanidins (PAs) in the presence of Cu prevented much of the damage, including plant growth and restoration of lignin synthesis which was inhibited in the presence of excess Cu. Transcriptome analyses of the impact of excess Cu and the amelioration after PAs treatment revealed that changes were enriched in functions associated with the cell wall and extracellular processes, indicating that inhibition of cell wall synthesis was likely the reason for retarded growth. Excess Cu appeared to induce a strong defense response, along with alterations in the expression of a number of genes encoding transcription factors, notably related to ethylene signaling. The addition of PAs greatly reduced this response, and also induced novel genes that likely help ameliorate the effects of excess Cu. These included induction of genes involved in the last step of ascorbic acid biosynthesis and of enzymes involved in cell wall synthesis. Combined, these results show that excess Cu causes severe oxidative stress damage and inhibition of cell wall synthesis, which can be relieved by the addition of PAs.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Nai-Chia Fan ◽  
Chih-Min Tsai ◽  
Chien-Ning Hsu ◽  
Li-Tung Huang ◽  
You-Lin Tain

Asymmetric dimethylarginine (ADMA) reduces nitric oxide (NO), thus causing hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH), which can be inhibited by oxidative stress. N-Acetylcysteine (NAC), an antioxidant, can facilitate glutathione (GSH) synthesis. We aimed to determine whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in spontaneously hypertensive rats (SHR). Rats aged 4 weeks were assigned into 3 groups (n=8/group): control Wistar Kyoto rats (WKY), SHR, and SHR receiving 2% NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal superoxide production was higher in SHR than in WKY, whereas NAC therapy prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The observed antihypertensive effects of NAC in young SHR might be due to restoration of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our findings highlight the impact of NAC on the development of hypertension by regulating ADMA-DDAH pathway.


2021 ◽  
Vol 1 ◽  
pp. 2
Author(s):  
Bernard W Downs ◽  
Samudra P. Banik ◽  
Manashi Bagchi ◽  
Bruce S. Morrison ◽  
Steve W. Kushner ◽  
...  

An increase in anaerobic (oxygen-deprived) pathogenesis significantly increases the generation of reactive oxygen species (ROS) inflicting damage on cell membranes and intracellular constituents. Generation of ROS and concomitant inflammatory response is the two hallmarks of cellular damage caused by cellular injury or invasion by pathogens. Oxygen deprivation, as opposed to oxygen deficiency, is a major contributor to oxidative stress and damage, cytokine production, and inflammation. When our cells are unable to efficiently and effectively utilize the oxygen to facilitate aerobic glycolysis and other cellular metabolic events, the oxygen instead oxidizes cell membranes, lipids, neurons, cross-links proteins, damages DNA, and initiates inflammation among other consequences. These anaerobic events are hallmarks of chronic degenerative diseases (CDD). Excessive demands to curtail oxidative damage can overburden endogenous antioxidative capabilities. A key treatment strategy to tackle the adverse effects of inflammation involves the augmentation of the structural integrity and functional competence of cellular materials, reducing the impact and consequences of tissue insult; the generation of ROS; and the cascade of subsequent pathological disorders. Moreover, restoration of cellular aerobic metabolic events, such as aerobic glycolysis and oxidative respiration, is an equally important collateral goal. A healthy diet and supplementation, providing an abundance of exogenous sources of antioxidants and a host of phytochemical dietary components, becomes even more important to restore aerobic metabolism; augment and assist in improving cellular structural integrity, and thereby reducing oxidative stress, damage, and inflammatory sequela. VMP35 MNC, a research-affirmed Prodosomed nutraceutical technology-based phytonutrient formulation, enriched in structurally diverse bioflavonoids, polyphenols, and phenolic saccharides, etc., have been shown to boost cellular structural integrity and physiological functions, and restore aerobic metabolic competence including for athletic performance as well as for general well-being. This review provides a strategic approach for the design of a novel Prodosomed VMP35 Multinutrient/phytoceutical complex and to evaluate its ability to reverse anaerobic pathologies, including inflammation, and restore healthy cellular aerobic glycolysis.


Life Sciences ◽  
2021 ◽  
Vol 264 ◽  
pp. 118653 ◽  
Author(s):  
Bianza Moise Bakadia ◽  
Biaou Oscar Ode Boni ◽  
Abeer Ahmed Qaed Ahmed ◽  
Guang Yang

2020 ◽  
Vol 19 (5) ◽  
pp. 336
Author(s):  
Luiza Minato Sagrillo ◽  
Viviane Nogueira De Zorzi ◽  
Luiz Fernando Freire Royes ◽  
Michele Rechia Fighera ◽  
Beatriz Da Silva Rosa Bonadiman ◽  
...  

Physical exercise has been shown to be an important modulator of the antioxidant system and neuroprotective in several diseases and treatments that affect the central nervous system. In this sense, the present study aimed to evaluate the effect of physical exercise in dynamic balance, motor coordination, exploratory locomotor activity and in the oxidative and immunological balance of rats treated with vincristine (VCR). For that, 40 adult rats were divided into two groups: exercise group (6 weeks of swimming, 1h/day, 5 days/week, with overload of 5% of body weight) and sedentary group. After training, rats were treated with 0.5 mg/kg of vincristine sulfate for two weeks or with the same dose of 0.9% NaCl. The behavioral tests were conducted 1 and 7 days after each dose of VCR. On day 15 we carried out the biochemical analyzes of the cerebellum. The physical exercise was able to protect against the loss of dynamic balance and motor coordination and, had effect per se in the exploratory locomotor activity, and neutralize oxidative stress, damage DNA and immune damage caused by VCR up to 15 days after the end of the training protocol. In conclusion, we observed that previous physical training protects of the damage motor induced by vincristine.Key-words: exercise, oxidative stress, neuroprotection, cerebellum.


2017 ◽  
Vol 68 (6) ◽  
pp. 1381-1383
Author(s):  
Allia Sindilar ◽  
Carmen Lacramioara Zamfir ◽  
Eusebiu Viorel Sindilar ◽  
Alin Constantin Pinzariu ◽  
Eduard Crauciuc ◽  
...  

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.


2020 ◽  
Vol 19 (6) ◽  
pp. 466-477
Author(s):  
Saïd Boujraf ◽  
Rachida Belaïch ◽  
Abdelkhalek Housni ◽  
Badreeddine Alami ◽  
Tariq Skalli ◽  
...  

Objective: The aim of this paper is to demonstrate the impact of hemodialysis (HD) using synthetic Helixone membrane on brain functional control reorganization and plasticity in the cortical area generated while Oxidative Stress (OS) would be the main impacting agent. Methods: Indeed, 9 chronic HD patients underwent identical brain BOLD-fMRI assessment using the motor paradigm immediately before and after the same HD sessions. To assess the oxidative stress, the same patients underwent biological-assessment, including Malondialdehyde (MDA) and Total- Antioxidant-Activity (TAOA) reported in earlier papers. Results: BOLD-fMRI maps of motor areas obtained from HD-patients before and after HD sessions revealed a significant enhancement of activation volume of the studied motor cortex after HD reflecting brain plasticity. Results were correlated with OS assessed by the measurement of MDA and TAOA; this correlation was close to 1. Conclusion: Indeed, HD enhances the inflammatory state of brain tissues reflected by the increased OS. The functional brain reaction demonstrated a functional activity reorganization to overcome the inflammatory state and OS enhanced by HD process. This functional activity reorganization reveals brain plasticity induced by OS originated by HD.


2012 ◽  
Vol 6 (2) ◽  
pp. 120-123 ◽  
Author(s):  
Oliver Gamondi ◽  
Sebastian Chapela ◽  
Ines Nievas ◽  
Isabel Burgos ◽  
Manuel Alonso ◽  
...  

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