scholarly journals Curcumin Improves the Renal Autophagy in Rat Experimental Membranous Nephropathy via Regulating the PI3K/AKT/mTOR and Nrf2/HO-1 Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qiu Di Tu ◽  
Juan Jin ◽  
Xiao Hu ◽  
Yan Ren ◽  
Li Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Membranous Nephropathy ◽  
Urine Volume ◽  
Underlying Mechanism ◽  
Scientific Basis ◽  
Immunofluorescence Assay ◽  
Normal Diet ◽  
Glomerular Diseases ◽  
Heymann Nephritis

Membranous nephropathy (MN, also known as membranous glomerulopathy) is one of the many glomerular diseases causing nephrotic syndrome. The literature indicates that autophagy is associated with the homeostasis of podocytes in glomeruli. Curcumin, the main active component in turmeric, has drawn attention for its effective bioactivities against chronic kidney disease. The current study was aimed at assessing the effects of curcumin and exploring the underlying mechanism that mediates autophagy in an animal model of passive Heymann nephritis (PHN) in rats. Passive Heymann nephritis (PHN) was induced in male SD rats by intraperitoneal injection of anti-Fx1A serum. The rats were divided into 3 groups: control ( n = 10 , normal diet), model group ( n = 10 , 0.5% sodium carboxymethylcellulose), and curcumin ( n = 10 , 300 mg/kg/d). The kidney function and oxidative stress indicators were measured using commercial diagnostic kits, and the histomorphology of renal tissues was observed. The number of podocytes was measured by immunohistochemistry. Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the immunofluorescence assay pointing to p62, an autophagic marker. Western blot analyzed the levels of apoptosis, autophagy, PI3K/AKT/mTOR, and Nrf2/HO-1 pathway-associated proteins. The total cholesterol (TC), triglycerides (TG), creatinine (Scr), blood urea nitrogen (BUN), urine volume, and urine albumin of PHN rats were significantly reduced by the administration of curcumin and attenuated renal histomorphological changes in model rats. Meanwhile, curcumin improved the oxidative stress response by decreasing MDA and increasing SOD, GSH, and CAT levels in the kidney of PHN rats. Furthermore, curcumin significantly ameliorated the podocyte loss, along with the fusion, and increased the autophagic vacuoles compared to the PHN control rats. In addition, curcumin downregulated the expression of Bax, Caspase-3, p62, PI3K, p-AKT, and p-mTOR proteins and upregulated the Bcl-2, beclin1, LC3, Nrf2, and HO-1 levels in this animal model. The results provide a scientific basis that curcumin could significantly alleviate the development of MN by inducing autophagy and alleviating renal oxidative stress through the PI3K/AKT/mTOR and Nrf2/HO-1 pathways.

scholarly journals Moringa oleiferaMitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chatchada Sutalangka ◽  
Jintanaporn Wattanathorn ◽  
Supaporn Muchimapura ◽  
Wipawee Thukham-mee
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Spatial Memory ◽  
Moringa Oleifera ◽  
Underlying Mechanism ◽  
Preventive Strategy ◽  
Neuron Density ◽  
Age Related ◽  
Male Wistar Rats

To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities ofMoringa oleifera, the enhancement of spatial memory and neuroprotection ofM. oleiferaleaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally givenM. oleiferaleaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest thatM. oleiferaleaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.

scholarly journals Antimetabolic Syndrome Effect of Phytosome Containing the Combined Extracts of Mulberry and Ginger in an Animal Model of Metabolic Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Nut Palachai ◽  
Jintanaporn Wattanathorn ◽  
Supaporn Muchimapura ◽  
Wipawee Thukham-mee
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Adipose Tissue ◽  
Body Weight Gain ◽  
Biological Activities ◽  
Health Benefit ◽  
Underlying Mechanism ◽  
Metabolic Parameter ◽  
Oxidative Stress Status

Due to the antimetabolic syndrome effect of mulberry and ginger together with the advantages of the synergistic effect and phytosome encapsulation technique, we hypothesized that phytosome containing the combined extracts of mulberry and ginger (PMG) should be able to manage MetS. PMG was developed and assessed the phenolic content and biological activities associated with the pathophysiology of MetS. The antimetabolic syndrome effect and the possible underlying mechanisms in the animal model of MetS were also assessed. Male Wistar rats induced MetS by subjecting to a 16-week high-carbohydrate high-fat diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg/kg for 21 days. They were determined metabolic parameter changes in serum, histomorphology changes of adipose tissue, the inflammatory cytokines such as IL-6 and TNF-α, oxidative stress status, PPAR-γ, and HDAC3 in adipose tissue. Our in vitro data showed that PMG increased phenolic contents and biological activities. PMG significantly improved MetS parameters including body weight gain, lipid profiles, plasma glucose, HOMA-IR, and ACE. In addition, the density and size of adipocyte, adiposity index, and weights of adipose tissues were also improved. Moreover, the decrease in TNF-α and IL-6, oxidative stress status, and HDAC3 expression together with the increase in PPAR-γ expression in adipose tissue was also observed. These data suggest that PMG exhibit antimetabolic syndrome and the possible underlying mechanism may be associated partly with the modulation effect on HDAC3, PPAR-γ, and adipose tissue. In addition, PMG also improves oxidative stress and inflammation in MetS. Therefore, PMG can be served as the potential supplement to manage MetS. However, a clinical trial study is essential to confirm this health benefit.

Nonalcoholic Fatty Liver Disease and Vitamin E - A Promising Relationship?

2019 ◽  
Vol 70 (1) ◽  
pp. 78-83
Author(s):  
Alexandra Totan ◽  
Daniela Gabriela Balan ◽  
Daniela Miricescu ◽  
Radu Radulescu ◽  
Iulia Ioana Stanescu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Therapeutic Potential ◽  
Plga Nanoparticles ◽  
Diet Group ◽  
Normal Diet ◽  
Oxidative Stress Biomarkers ◽  
Promising Alternative ◽  
Nonalcoholic Fatty Liver ◽  
High Caloric Diet

Oxidative stress (OS) plays an important role in NAFLD molecular mechanism. Nanoencapsulation represents a novel strategy to enhance therapeutic potential of conventional drugs. Our study analyses the encapsulated vitamin E effect on lipid metabolism and oxidative stress biomarkers in NAFLD rats. Animals were divided into 3 groups : G1 - the normal diet group; G2- the high caloric diet group ; G3 - high-caloric diet group receiving PLGA-vit E, 50 mg / kg. Serum advanced human oxidative protein (AOPP), total antioxidant capacity (TAC) and vitamin E were analysed using ELISA technique. Our results showed significant increase of G2 GPT, ALP, GGT, TG, glucose, TC and AOPP, versus G1 ( P [ 0.05) and a significant decrease of G2 serum TAC and vitamin E versus G1 results ( p = 0.01 and 0.01). Vitamin E nanoparticles (G3) caused a significant increase of TAC and significant decrease of serum AOPP, versus G2 (p [ 0.01). Results showed a significant reduction of GPT, GGT, ALP, TG and total cholesterol ( p [0.05) in G3 versus G2. PLGA nanoparticles should be considered an attractive and promising alternative to improve the bioavailability and biological activity of vitaminE.

scholarly journals Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomonori Hara ◽  
Manabu Toyoshima ◽  
Yasuko Hisano ◽  
Shabeesh Balan ◽  
Yoshimi Iwayama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Caspase 3 ◽  
Intervention Strategy ◽  
Underlying Mechanism ◽  
Carbonyl Stress ◽  
Gene Encoding ◽  
Induced Pluripotent

AbstractCarbonyl stress, a specific form of oxidative stress, is reported to be involved in the pathophysiology of schizophrenia; however, little is known regarding the underlying mechanism. Here, we found that disruption of GLO1, the gene encoding a major catabolic enzyme scavenging the carbonyl group, increases vulnerability to external carbonyl stress, leading to abnormal phenotypes in human induced pluripotent stem cells (hiPSCs). The viability of GLO1 knockout (KO)-hiPSCs decreased and activity of caspase-3 was increased upon addition of methylglyoxal (MGO), a reactive carbonyl compound. In the GLO1 KO-hiPSC-derived neurons, MGO administration impaired neurite extension and cell migration. Further, accumulation of methylglyoxal-derived hydroimidazolone (MG-H1; a derivative of MGO)-modified proteins was detected in isolated mitochondria. Mitochondrial dysfunction, including diminished membrane potential and dampened respiratory function, was observed in the GLO1 KO-hiPSCs and derived neurons after addition of MGO and hence might be the mechanism underlying the effects of carbonyl stress. The susceptibility to MGO was partially rescued by the administration of pyridoxamine, a carbonyl scavenger. Our observations can be used for designing an intervention strategy for diseases, particularly those induced by enhanced carbonyl stress or oxidative stress.

scholarly journals SHR/NCrl rats as a model of ADHD can be discriminated from controls based on their brain, blood, or urine metabolomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Camille Dupuy ◽  
Pierre Castelnau ◽  
Sylvie Mavel ◽  
Antoine Lefevre ◽  
Lydie Nadal-Desbarats ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Attention Deficit Hyperactivity Disorder ◽  
Animal Model ◽  
Metabolic Pathways ◽  
Neurodevelopmental Disorder ◽  
Hyperactivity Disorder ◽  
Pathophysiological Condition ◽  
The Brain ◽  
And Oxidative Stress ◽  
Peripheral Samples

AbstractAttention-Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. The neurobiological mechanisms underlying ADHD are still poorly understood, and its diagnosis remains difficult due to its heterogeneity. Metabolomics is a recent strategy for the holistic exploration of metabolism and is well suited for investigating the pathophysiology of diseases and finding molecular biomarkers. A few clinical metabolomic studies have been performed on peripheral samples from ADHD patients but are limited by their access to the brain. Here, we investigated the brain, blood, and urine metabolomes of SHR/NCrl vs WKY/NHsd rats to better understand the neurobiology and to find potential peripheral biomarkers underlying the ADHD-like phenotype of this animal model. We showed that SHR/NCrl rats can be differentiated from controls based on their brain, blood, and urine metabolomes. In the brain, SHR/NCrl rats displayed modifications in metabolic pathways related to energy metabolism and oxidative stress further supporting their importance in the pathophysiology of ADHD bringing news arguments in favor of the Neuroenergetic theory of ADHD. Besides, the peripheral metabolome of SHR/NCrl rats also shared more than half of these differences further supporting the importance of looking at multiple matrices to characterize a pathophysiological condition of an individual. This also stresses out the importance of investigating the peripheral energy and oxidative stress metabolic pathways in the search of biomarkers of ADHD.

Myrtenol complexed with β‐cyclodextrin ameliorates behavioral deficits and reduces oxidative stress in the reserpine‐induced animal model of parkinsonism

2021 ◽  
Author(s):  
Suellen Silva‐Martins ◽  
Jose Ivo Araújo Beserra‐Filho ◽  
Amanda Maria‐Macêdo ◽  
Ana Cláudia Custódio‐Silva ◽  
Beatriz Soares‐Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Behavioral Deficits

scholarly journals Oxidative Stress and Cognitive Alterations Induced by Cancer Chemotherapy Drugs: A Scoping Review

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1116
Author(s):  
Omar Cauli
Keyword(s):  
Oxidative Stress ◽  
Cancer Patients ◽  
Repeated Administration ◽  
Caffeic Acid Phenethyl Ester ◽  
Scientific Basis ◽  
Clinical Settings ◽  
Chemotherapy Drugs ◽  
Scientific Attention ◽  
The Brain ◽  
Cognitive Alterations

Cognitive impairment is one of the most deleterious effects of chemotherapy treatment in cancer patients, and this problem sometimes remains even after chemotherapy ends. Common classes of chemotherapy-based regimens such as anthracyclines, taxanes, and platinum derivatives can induce both oxidative stress in the blood and in the brain, and these effects can be reproduced in neuronal and glia cell cultures. In rodent models, both the acute and repeated administration of doxorubicin or adriamycin (anthracyclines) or cisplatin impairs cognitive functions, as shown by their diminished performance in different learning and memory behavioural tasks. Administration of compounds with strong antioxidant effects such as N-acetylcysteine, gamma-glutamyl cysteine ethyl ester, polydatin, caffeic acid phenethyl ester, and 2-mercaptoethane sulfonate sodium (MESNA) counteract both oxidative stress and cognitive alterations induced by chemotherapeutic drugs. These antioxidant molecules provide the scientific basis to design clinical trials in patients with the aim of reducing the oxidative stress and cognitive alterations, among other probable central nervous system changes, elicited by chemotherapy in cancer patients. In particular, N-acetylcysteine and MESNA are currently used in clinical settings and are therefore attracting scientific attention.

scholarly journals Podocyte injury: the role of proteinuria, urinary plasminogen, and oxidative stress

2016 ◽  
Vol 311 (6) ◽  
pp. F1308-F1317 ◽  
Author(s):  
Leopoldo Raij ◽  
Runxia Tian ◽  
Jenny S. Wong ◽  
John C. He ◽  
Kirk N. Campbell
Keyword(s):  
Oxidative Stress ◽  
Glomerular Filtration ◽  
Biologically Active ◽  
Current Evidence ◽  
Glomerular Sclerosis ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Filtration Barrier ◽  
Focal Segmental Glomerular Sclerosis

Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA). In vivo inhibition of uPA mitigates Plg activation and development of FSGS in several proteinuric models of renal disease including 5/6 nephrectomy. Here, we show that Plg is markedly increased in the urine in two murine models of proteinuric kidney disease associated with podocyte injury: Tg26 HIV-associated nephropathy and the Cd2ap −/− model of FSGS. We show that human podocytes express uPA and three Plg receptors: uPAR, tPA, and Plg-RKT. We demonstrate that Plg treatment of podocytes specifically upregulates NADPH oxidase isoforms NOX2/NOX4 and increases production of mitochondrial-dependent superoxide anion (O2−) that promotes endothelin-1 synthesis. Plg via O2− also promotes expression of the B scavenger receptor CD36 and subsequent increased intracellular cholesterol uptake resulting in podocyte apoptosis. Taken together, our findings suggest that following disruption of the glomerular filtration barrier at the onset of proteinuric disease, podocytes are exposed to Plg resulting in further injury mediated by oxidative stress. We suggest that chronic exposure to Plg could serve as a “second hit” in glomerular disease and that Plg is potentially an attractive target for therapeutic intervention.

PARP inhibition ameliorates nephropathy in an animal model of type 2 diabetes: focus on oxidative stress, inflammation, and fibrosis

2017 ◽  
Vol 390 (6) ◽  
pp. 621-631 ◽  
Author(s):  
Esraa M. Zakaria ◽  
Nabila N. El-Maraghy ◽  
Ahmed F. Ahmed ◽  
Abdelmonim A. Ali ◽  
Hany M. El-Bassossy
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Animal Model ◽  
Parp Inhibition

scholarly journals Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

2010 ◽  
Vol 299 (4) ◽  
pp. R1082-R1090 ◽  
Author(s):  
Jill K. Morris ◽  
Gregory L. Bomhoff ◽  
John A. Stanford ◽  
Paige C. Geiger
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Locomotor Activity ◽  
Substantia Nigra ◽  
High Fat Diet ◽  
Model Assessment ◽  
High Fat

Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.

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