scholarly journals Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

2015 ◽  
Vol 35 (3) ◽  
pp. 1241-1251 ◽  
Author(s):  
Haider Raza ◽  
Annie John ◽  
Frank Christopher Howarth
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Rat Liver ◽  
Redox Homeostasis ◽  
Glutathione Metabolism ◽  
Rat Tissues ◽  
No Production ◽  
Altered Expression ◽  
Zdf Rat ◽  
Zdf Rats

Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA) rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS) production in the ZDF rat brain compared to the liver, while nitric oxide (NO) production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA) control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

scholarly journals Investigations into the Role of Metabolism in the Inflammatory Response of BV2 Microglial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 109
Author(s):  
Pamela Maher
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Enzyme Inhibitors ◽  
Carbon Sources ◽  
Microglial Cells ◽  
No Production ◽  
Low Grade ◽  
Potent Inducer ◽  
Lps Activation ◽  
Bv2 Microglial Cells

Although the hallmarks of Alzheimer’s disease (AD) are amyloid beta plaques and neurofibrillary tangles, there is growing evidence that neuroinflammation, mitochondrial dysfunction and oxidative stress play important roles in disease development and progression. A major risk factor for the development of AD is diabetes, which is also characterized by oxidative stress and mitochondrial dysfunction along with chronic, low-grade inflammation. Increasing evidence indicates that in immune cells, the induction of a pro-inflammatory phenotype is associated with a shift from oxidative phosphorylation (OXPHOS) to glycolysis. However, whether hyperglycemia also contributes to this shift is not clear. Several different approaches including culturing BV2 microglial cells in different carbon sources, using enzyme inhibitors and knocking down key pathway elements were used in conjunction with bacterial lipopolysaccharide (LPS) activation to address this question. The results indicate that while high glucose favors NO production, pro-inflammatory cytokine production is highest in the presence of carbon sources that drive OXPHOS. In addition, among the carbon sources that drive OXPHOS, glutamine is a very potent inducer of IL6 production. This effect is dampened in the presence of glucose. Together, these results may provide new prospects for the therapeutic manipulation of neuroinflammation in the context of diabetes and AD.

scholarly journals Virulence of Streptococcus pneumoniae: PsaA Mutants Are Hypersensitive to Oxidative Stress

2002 ◽  
Vol 70 (3) ◽  
pp. 1635-1639 ◽  
Author(s):  
Hsing-Ju Tseng ◽  
Alastair G. McEwan ◽  
James C. Paton ◽  
Michael P. Jennings
Keyword(s):  
Oxidative Stress ◽  
Streptococcus Pneumoniae ◽  
Stress Response ◽  
Nadh Oxidase ◽  
Redox Homeostasis ◽  
Oxidative Stress Response ◽  
Wild Type ◽  
Regulation Of Expression ◽  
Altered Expression ◽  
Transport Complex

ABSTRACT psaA encodes a 37-kDa pneumococcal lipoprotein which is part of an ABC Mn(II) transport complex. Streptococcus pneumoniae D39 psaA mutants have previously been shown to be significantly less virulent than wild-type D39, but the mechanism underlying the attenuation has not been resolved. In this study, we have shown that psaA and psaD mutants are highly sensitive to oxidative stress, i.e., to superoxide and hydrogen peroxide, which might explain why they are less virulent than the wild-type strain. Our investigations revealed altered expression of the key oxidative-stress response enzymes superoxide dismutase and NADH oxidase in psaA and psaD mutants, suggesting that PsaA and PsaD may play important roles in the regulation of expression of oxidative-stress response enzymes and intracellular redox homeostasis.

scholarly journals Alterations in Energy Metabolism, Mitochondrial Function and Redox Homeostasis in GK Diabetic Rat Tissues Treated with Aspirin

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 104
Author(s):  
Annie John ◽  
Layla Amiri ◽  
Jasmin Shafarin ◽  
Saeed Tariq ◽  
Ernest Adeghate ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Redox Homeostasis ◽  
Diabetic Rats ◽  
Endocrine Function ◽  
Diabetic Rat ◽  
Rat Tissues ◽  
Gk Rats ◽  
And Oxidative Stress

Our recent studies have demonstrated that aspirin treatment prevents inflammatory and oxidative stress-induced alterations in mitochondrial function, improves glucose tolerance and pancreatic endocrine function and preserves tissue-specific glutathione (GSH)-dependent redox homeostasis in Goto-Kakizaki (GK) diabetic rats. In the current study, we have investigated the mechanism of action of aspirin in maintaining mitochondrial bioenergetics and redox metabolism in the liver and kidneys of GK rats. Aspirin reduced the production of reactive oxygen species (ROS) and oxidative stress-induced changes in GSH metabolism. Aspirin treatment also improved mitochondrial respiratory function and energy metabolism, in addition to regulating the expression of cell signaling proteins that were altered in diabetic animals. Ultrastructural electron microscopy studies revealed decreased accumulation of glycogen in the liver of aspirin-treated diabetic rats. Hypertrophic podocytes with irregular fusion of foot processes in the renal glomerulus and detached microvilli, condensed nuclei and degenerated mitochondria observed in the proximal convoluted tubules of GK rats were partially restored by aspirin. These results provide additional evidence to support our previous observation of moderation of diabetic complications by aspirin treatment in GK rats and may have implications for cautious use of aspirin in the therapeutic management of diabetes.

scholarly journals Elucidation of Molecular Mechanisms of Streptozotocin-Induced Oxidative Stress, Apoptosis, and Mitochondrial Dysfunction in Rin-5F Pancreatic β-Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Arwa M. T. Al Nahdi ◽  
Annie John ◽  
Haider Raza
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Dependent Manner ◽  
Respiratory Enzymes ◽  
Altered Expression ◽  
Pancreatic Cancer Cells

Streptozotocin is a pancreatic beta-cell-specific cytotoxin and is widely used to induce experimental type 1 diabetes in rodent models. The precise molecular mechanism of STZ cytotoxicity is however not clear. Studies have suggested that STZ is preferably absorbed by insulin-secreting β-cells and induces cytotoxicity by producing reactive oxygen species/reactive nitrogen species (ROS/RNS). In the present study, we have investigated the mechanism of cytotoxicity of STZ in insulin-secreting pancreatic cancer cells (Rin-5F) at different doses and time intervals. Cell viability, apoptosis, oxidative stress, and mitochondrial bioenergetics were studied. Our results showed that STZ induces alterations in glutathione homeostasis and inhibited the activities of the respiratory enzymes, resulting in inhibition of ATP synthesis. Apoptosis was observed in a dose- and time-dependent manner. Western blot analysis has also confirmed altered expression of oxidative stress markers (e.g., NOS and Nrf2), cell signaling kinases, apoptotic protein-like caspase-3, PARP, and mitochondrial specific proteins. These results suggest that STZ-induced cytotoxicity in pancreatic cells is mediated by an increase in oxidative stress, alterations in cellular metabolism, and mitochondrial dysfunction. This study may be significant in better understanding the mechanism of STZ-induced β-cell toxicity/resistance and the etiology of type 1 diabetes induction.

scholarly journals Oxidative Stress in DNA Repeat Expansion Disorders: A Focus on NRF2 Signaling Involvement

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 702 ◽  
Author(s):  
Piergiorgio La Rosa ◽  
Sara Petrillo ◽  
Enrico Silvio Bertini ◽  
Fiorella Piemonte
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Protein Expression ◽  
Mitochondrial Dysfunction ◽  
Redox Homeostasis ◽  
Regulatory Region ◽  
Antioxidant Response ◽  
Repeat Expansion ◽  
Common Features ◽  
Dna Repeat

DNA repeat expansion disorders are a group of neuromuscular and neurodegenerative diseases that arise from the inheritance of long tracts of nucleotide repetitions, located in the regulatory region, introns, or inside the coding sequence of a gene. Although loss of protein expression and/or the gain of function of its transcribed mRNA or translated product represent the major pathogenic effect of these pathologies, mitochondrial dysfunction and imbalance in redox homeostasis are reported as common features in these disorders, deeply affecting their severity and progression. In this review, we examine the role that the redox imbalance plays in the pathological mechanisms of DNA expansion disorders and the recent advances on antioxidant treatments, particularly focusing on the expression and the activity of the transcription factor NRF2, the main cellular regulator of the antioxidant response.

scholarly journals Exploring marine resources against neurological disorders– the neuroprotective and anti-inflammatory potential of the brown seaweed Bifurcaria bifurcata

2021 ◽  
Author(s):  
Joana Silva ◽  
Celso Alves ◽  
Patricia Susano ◽  
Alice Martins ◽  
Susete Pinteus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Caspase 3 ◽  
Tissue Injury ◽  
Radical Scavenging ◽  
Brown Seaweed ◽  
No Production ◽  
Antioxidant Power ◽  
Bifurcaria Bifurcata ◽  
Anti Inflammatory

Abstract Oxidative stress is strongly involved in the pathogenesis of neurodegenerative diseases, like Parkinson´s disease (PD). Particularly, an excess of reactive oxygen species (ROS) released by the cells promotes an oxidative stress condition, which is a main cause of tissue injury leading to nervous system dysfunction. In this work, the antioxidant, neuroprotective and anti-inflammatory activities of different fractions from Bifurcaria bifurcata are presented and related with their chemical profile. The antioxidant capacity was evaluated by the Folin-Ciocalteu method, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Neuroprotective capacity was evaluated to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells, and their anti-inflammatory effects on RAW 264.7 macrophages. Regarding results, ethyl acetate fractions (100 µg/mL) exhibited significant antioxidant and neuroprotective activities in the in vitro models assayed. Furthermore, two of the most polar fractions obtained with methanol and water, also evidenced a significant neuroprotective potential. B. bifurcata fractions treatment decreased ROS production, mitochondrial dysfunction, and Caspase-3 activity. Regarding the anti-inflammatory potential, five fractions (100 µg/mL) inhibited nitric oxide (NO) production and reduced the interleukin – 6 (IL-6) and tumor necrosis factor (TNF-α) levels. Mannitol, identified as the major component of the most bioactive fraction, protected SH-SY5Y cells against the 6-OHDA neurotoxicity mediating ROS generation mitigation, mitochondrial dysfunction, and DNA damage, together with the Caspase-3 activity inhibition. Results suggest that B. bifurcata is a relevant source of neuroprotective agents, with particular interest for preventive therapeutics.

In vivo evidence that bezafibrate prevents oxidative stress and mitochondrial dysfunction caused by 3-methylglutaric acid in rat liver

Biochimie ◽  
2020 ◽  
Vol 171-172 ◽  
pp. 187-196
Author(s):  
Nevton Teixeira da Rosa-Junior ◽  
Belisa Parmeggiani ◽  
Nícolas Manzke Glänzel ◽  
Leonardo de Moura Alvorcem ◽  
Marina Rocha Frusciante ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Rat Liver
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