N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress

2003 ◽  
Vol 285 (4) ◽  
pp. E744-E753 ◽  
Author(s):  
C. Andrew Haber ◽  
Tony K. T. Lam ◽  
Zhiwen Yu ◽  
Neehar Gupta ◽  
Tracy Goh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
High Glucose ◽  
Muscle Protein ◽  
Fold Increase ◽  
Protein Carbonyl ◽  
Protein Carbonyl Content ◽  
High Concentrations

Exposure to high concentrations of glucose and insulin results in insulin resistance of metabolic target tissues, a characteristic feature of type 2 diabetes. High glucose has also been associated with oxidative stress, and increased levels of reactive oxygen species have been proposed to cause insulin resistance. To determine whether oxidative stress contributes to insulin resistance induced by hyperglycemia in vivo, nondiabetic rats were infused with glucose for 6 h to maintain a circulating glucose concentration of 15 mM with and without coinfusion of the antioxidant N-acetylcysteine (NAC), followed by a 2-h hyperinsulinemic-euglycemic clamp. High glucose (HG) induced a significant decrease in insulin-stimulated glucose uptake [tracer-determined disappearance rate (Rd), control 41.2 ± 1.7 vs. HG 32.4 ± 1.9 mg · kg–1 · min–1, P < 0.05], which was prevented by NAC (HG + NAC 45.9 ± 3.5 mg · kg–1 · min–1). Similar results were obtained with the antioxidant taurine. Neither NAC nor taurine alone altered Rd. HG caused a significant (5-fold) increase in soleus muscle protein carbonyl content, a marker of oxidative stress that was blocked by NAC, as well as elevated levels of malondialdehyde and 4-hydroxynonenal, markers of lipid peroxidation, which were reduced by taurine. In contrast to findings after long-term hyperglycemia, there was no membrane translocation of novel isoforms of protein kinase C in skeletal muscle after 6 h. These data support the concept that oxidative stress contributes to the pathogenesis of hyperglycemia-induced insulin resistance.

Fluoride induced oxidative stress, immune system and apoptosis in animals: a review

2016 ◽  
Vol 5 (12) ◽  
pp. 5174 ◽  
Author(s):  
Arup Giri ◽  
Vijay Kumar Bharti* ◽  
Kunzes Angmo ◽  
Sahil Kalia ◽  
Bhuvnesh Kumar
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Protein Carbonyl ◽  
Experimental Models ◽  
Cellular Systems ◽  
Human Populations ◽  
Protein Carbonyl Content ◽  
Good Reputation ◽  
High Concentrations

Halfway through the twentieth century, fluoride piqued the interest of toxicologists due to its deleterious effects due to high concentrations in animals as well as in human populations suffering from several types of disorders and in in-vivo experimental models. Until the 1990s, the toxicity of fluoride was largely ignored due to its “good reputation” for preventing caries via topical application and in dental toothpaste. However, in the last decade, interest in its undesirable effects has resurfaced due to the awareness that this element interacts with cellular systems even at low doses. In recent years, several investigations demonstrated that fluoride can induce oxidative stress and modulate intracellular redox homoeostasis; lipid peroxidation and protein carbonyl content, as well as alter gene expression and cause apoptosis. Genes modulated by fluoride include those related to the stress response, metabolic enzymes, the cell cycle, cell–cell communications and signal transduction. The primary purpose of this review is to examine recent findings on the effects of fluoride on oxidative stress, immune system and apoptosis in the animal as well as in human system.

scholarly journals Effect of N-acetyl-l-cysteine on insulin resistance caused by prolonged free fatty acid elevation

2015 ◽  
Vol 225 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Sandra Pereira ◽  
Anu Shah ◽  
I George Fantus ◽  
Jamie W Joseph ◽  
Adria Giacca
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Muscle Protein ◽  
Protein Carbonyl ◽  
Hepatic Insulin Resistance ◽  
Skeletal Muscle Protein ◽  
Protein Carbonyl Content ◽  
Peripheral Insulin Resistance ◽  
Plasma Ffa

Circulating free fatty acids (FFAs) are elevated in obesity and cause insulin resistance. The objective of the current study was to determine whether the antioxidantN-acetyl-l-cysteine (NAC) prevented hepatic and peripheral insulin resistance caused by prolonged elevation of plasma FFAs. Chronically cannulated Wistar rats received saline (SAL), Intralipid plus heparin (IH), IH plus NAC, or NAC i.v. infusion for 48 h. Insulin sensitivity was determined using the hyperinsulinemic–euglycemic clamp with tritiated glucose tracer. IH induced hepatic and peripheral insulin resistance (P<0.05). NAC co-infusion did not prevent insulin resistance in the liver, although it was able to prevent peripheral insulin resistance. Prolonged IH infusion did not appear to induce oxidative stress in the liver because hepatic content of protein carbonyl, malondialdehyde, and reduced to oxidized glutathione ratio did not differ across treatment groups. In alignment with our insulin sensitivity results, IH augmented skeletal muscle protein carbonyl content and this was prevented by NAC co-infusion. Taken together, our results indicate that oxidative stress mediates peripheral, but not hepatic, insulin resistance resulting from prolonged plasma FFA elevation. Thus, in states of chronic plasma FFA elevation, such as obesity, antioxidants may protect against peripheral but not hepatic insulin resistance.

scholarly journals Neuroprotective Effect of Dioscin on the Aging Brain

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1247 ◽  
Author(s):  
Yan Qi ◽  
Ruomiao Li ◽  
Lina Xu ◽  
Lianhong Yin ◽  
Youwei Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Brain Aging ◽  
Neuroprotective Effect ◽  
Protein Carbonyl ◽  
Learning Ability ◽  
Aging Brain ◽  
Protein Carbonyl Content

Our previous works have shown that dioscin, a natural product, has various pharmacological activities, however, its role in brain aging has not been reported. In the present study, in vitro H2O2-treated PC12 cells and in vivo d-galactose-induced aging rat models were used to evaluate the neuroprotective effect of dioscin on brain aging. The results showed that dioscin increased cell viability and protected PC12 cells against oxidative stress through decreasing reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels. In vivo, dioscin markedly improved the spatial learning ability and memory of aging rats, reduced the protein carbonyl content and aging cell numbers, restored the levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and nitric oxide synthase (NOS) in brain tissue, and reversed the histopathological structure changes of nerve cells. Mechanism studies showed that dioscin markedly adjusted the MAPK and Nrf2/ARE signalling pathways to decrease oxidative stress. Additionally, dioscin also significantly decreased inflammation by inhibiting the mRNA or protein levels of TNF-α, IL-1β, IL-6, CYP2E1 and HMGB1. Taken together, these results indicate that dioscin showed neuroprotective effect against brain aging via decreasing oxidative stress and inflammation, which should be developed as an efficient candidate in clinical to treat brain aging in the future.

scholarly journals DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells

2022 ◽  
Vol 12 ◽  
Author(s):  
Xuguang Zhang ◽  
Yuxin Zhang ◽  
Mingyan Zhou ◽  
Yiqiang Xie ◽  
Xiujuan Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
High Glucose ◽  
Hepg2 Cells ◽  
Fasting Blood Glucose ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Alpinia Officinarum

(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.

Alteration in the oxidative status of Drosophila melanogaster Meigen (Diptera: Drosophilidae) fed with a diet containing Centaurea depressa M. Bieb. (Asteraceae)

2020 ◽  
Vol 70 (2) ◽  
pp. 227-237
Author(s):  
Eda Güneş
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Total Protein ◽  
Protein Carbonyl ◽  
Control Group ◽  
Carbonyl Content ◽  
Protein Carbonyl Content ◽  
Freeze Dried ◽  
Dried Extract

Abstract The aim of the this study was to evaluate the effects of fresh, dried and freeze-dried Centaurea depressa M. Bieb. (Asteraceae) on the oxidant and antioxidant status of the model organism D. melanogaster Meigen (Diptera: Drosophilidae) experimentally. The study was carried out from 2016 to 2019, and plant leaf extracts (0-50 mg/l) were added to insect standard artificial diets. The total protein, protein carbonyl content and glutathione-S-transferase, superoxide dismutase and catalase activities were quantified at the insect’s third larval stage. Our data showed that protein carbonyl content varied from 2.70 nmol/mg protein in the control group to 59.11 nmol/mg protein in the group fed with fresh leaf extract signifying induction of oxidative stress. All extracts increased the levels of all antioxidant enzymes and decreased the amounts of total protein. Meanwhile, the group fed with the freeze-dried extract showed no significant difference in the levels of total protein and protein carbonyl content except at the 50 mg/l concentration of the extract. Moreover, this group had superoxide dismutase and catalase activities 4 to 5 times higher than in the control group. In conclusion, induction of oxidative stress indicates that the fresh form of C. depressa leaves may have potential as a natural pesticide, whereas induction of endogenous antioxidant enzymes by the freeze-dried extract suggest its potential as an antioxidant.

Abstract 424: Vascular Smooth Muscle Cell Expression of S100a12 in Vivo Induces Enhanced Oxidative Stress & Vascular Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marion Hofmann Bowman ◽  
Jeannine Wilk ◽  
Gene Kim ◽  
Yanmin Zhang ◽  
Jalees Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Oxidative Dna Damage ◽  
Fold Increase ◽  
Brdu Incorporation ◽  
Elastic Fibers ◽  
Nuclear Staining

S100A12 is a small calcium binding protein that is a signal transduction ligand of the receptor for advance glycation endproducts (RAGE). S100A12, like RAGE, is expressed in the vessel wall of atherosclerotic vasculature, particularly in smooth muscle cells (SMC). While RAGE has been extensively implicated in inflammatory states such as atherosclerosis, the role of S100A12 is less clear. We tested the hypothesis that expression of human S100A12 directly exacerbates vascular inflammation. Several lines of Bl6/J transgenic mice (tg) expressing human S100A12 in SMC under control of the SM22a promoter were generated. Primary aortic SMC from tg and wild type (wt) littermates were isolated and analyzed for (i) proliferation using MTS/Formazan Assay and BrdU incorporation, (ii) oxidative stress using using flow cytometry with MitoSOX antibody, oxidative DNA damage using immunofluorescence microscopy with anti-8-oxo-dG antibody, and NF-kB activation measured by EMSA and (iii) cytokine expression measured by IL-6 ELISA. Furthermore, the aortas from tg and wt mice were examined. Results: Tg but not wt SMC expressed S100A12 protein. Tg SMC had a significant 1.9 to 2.7 fold increase in conversion of MTS into Formazan at 24–96 hours likely reflective of increased metabolic activity since BrdU incorporation into DNA was less in tg compared to wt SMC (4% vs 21% positive BrdU nuclei, p <0.05). Tg SMC showed significantly higher levels of mitochondrial generated ROS, nuclear staining for oxidative DNA damage which was not detected in the nuclei of wt SMC’s, and a 2.5 fold increase in NFkB activity. IL-6 production at baseline was higher in tg SMC’s (615 vs 213 pg/ml, p< 0.05) and increased dramatically after LPS treatment (10 ng/ml) in tg SMC’s (2130 vs 415 pg/ml). Histologic examination of the thoracic aorta at 10 weeks of age revealed increased collagen deposition in the aortic media with fragmentation and disarray of elastic fibers. In vivo ultrasound revealed a progressive dilation of the aortic arch from age 10 weeks to 16 weeks of age (1.27 to 1.60 mm, p<0.05) in tg but not in wt littermate mice (1.30 to 1.33 mm, p=0.1). These data reveal the novel finding that targeted expression of human S100A12 in SMC modulates oxidative stress, inflammation and vascular remodeling.

scholarly journals Protein carbonyls and protein thiols in rheumatoid arthritis

2018 ◽  
Vol 6 (5) ◽  
pp. 1738 ◽  
Author(s):  
Pullaiah P. ◽  
Suchitra M. M. ◽  
Siddhartha Kumar B.
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Protein Modification ◽  
Antioxidant Properties ◽  
Protein Carbonyl ◽  
Protein Carbonyls ◽  
Carbonyl Content ◽  
Protein Thiol ◽  
Protein Carbonyl Content ◽  
Protein Thiols

Background: Oxidative stress (OS) has an important role in the pathogenesis and progression of rheumatoid arthritis (RA). OS causes protein modification, thereby impairing the biological functions of the protein. This study was conducted to assess the oxidatively modified protein as protein carbonyl content and the antioxidant status as protein thiols, and to study the association between protein carbonyls and protein thiols in RA.Methods: Newly diagnosed RA patients who were not taking any disease modifying anti-rheumatic drugs were included into the study group (n=45) along with age and sex matched healthy controls (n=45). Serum protein carbonyl content and protein thiols were estimated.Results: Elevated protein carbonyl content and decreased protein thiol levels (p<0.001) were observed in RA. A significant negative correlation was observed between protein carbonyl content and protein thiol levels (p<0.001).Conclusions: Oxidative stress in RA is evidenced by enhanced protein oxidation and decreased antioxidant protein thiol levels. Decreased protein thiols may also reflect protein modifications leading to compromise in the antioxidant properties. This oxidant and antioxidant imbalance needs to be addressed by therapeutic interventions to prevent disease progression.

scholarly journals Studies of the long-term regulation of hepatic pyruvate dehydrogenase kinase

1998 ◽  
Vol 329 (1) ◽  
pp. 89-94 ◽  
Author(s):  
C. Mary SUGDEN ◽  
G. D. Lee FRYER ◽  
A. Karen ORFALI ◽  
A. David PRIESTMAN ◽  
Elaine DONALD ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Pyruvate Dehydrogenase ◽  
Unsaturated Fatty Acids ◽  
Fold Increase ◽  
Membrane Lipid ◽  
Dietary Lipid ◽  
Pyruvate Dehydrogenase Kinase ◽  
Plasma Insulin Concentration

The administration of a low-carbohydrate/high-saturated-fat (LC/HF) diet for 28 days or starvation for 48 h both increased pyruvate dehydrogenase kinase (PDHK) activity in extracts of rat hepatic mitochondria, by approx. 2.1-fold and 3.5-fold respectively. ELISAs of extracts of hepatic mitochondria, conducted over a range of pyruvate dehydrogenase (PDH) activities, revealed that mitochondrial immunoreactive PDHKII (the major PDHK isoform in rat liver) was significantly increased by approx. 1.4-fold after 28 days of LC/HF feeding and by approx. 2-fold after 48 h of starvation. The effect of LC/HF feeding to increase hepatic PDHK activity was retained through hepatocyte preparation, but was decreased on 21 h culture with insulin (100μ-i.u./ml). A sustained (24 h) 2-4-fold elevation in plasma insulin concentration in vivo (achieved by insulin infusion via an osmotic pump) suppressed the effect of LC/HF feeding so that hepatic PDHK activities did not differ significantly from those of (insulin-infused) control rats. The increase in hepatic PDHK activity evoked by 28 days of LC/HF feeding was prevented and reversed (within 24 h) by the replacement of 7% of the dietary lipid with long-chain ω-3 fatty acids. Analysis of hepatic membrane lipid revealed a 1.9-fold increase in the ratio of total polyunsaturated ω-3 fatty acids to total mono-unsaturated fatty acids. The results indicate that the increased hepatic PDHK activities observed in livers of LC/HF-fed or 48 h-starved rats are associated with long-term actions to increase hepatic PDHKII concentrations. The long-term regulation of hepatic PDHK by LC/HF feeding might be achieved through an impaired action of insulin to suppress PDHK activity. In addition, the fatty acid composition of the diet, rather than the fat content, is a key influence.

Effect of GSH and niacin combination on protein oxidation, ER stress, glycation and aggregation in HLE cells under high glucose condition

2021 ◽  
Vol 2 (1) ◽  
pp. 1-5
Author(s):  
Nina Handayani ◽  
◽  
Hidayat Sujuti ◽  
Achmad Rudijanto ◽  
◽  
...  
Keyword(s):  
Er Stress ◽  
High Glucose ◽  
Active Role ◽  
Protein Carbonyl ◽  
Human Lens ◽  
Control Group ◽  
High Dose ◽  
Protein Carbonyl Content ◽  
Glucose Levels ◽  
High Glucose Condition

AIM: To evaluate the effects of reduced glutathione (GSH) and niacin combination on protein oxidative stress, endoplasmic reticulum (ER) stress, glycation, and aggregation of the αβ crystalline in human lens epithelial (HLE) cells treated with high glucose levels. METHODS: HLE cells were cultured and exposed to 25 mmol/L glucose to promote high glucose conditions. Groups of cells were co-treated with three different combinations of dosages: 10 μmol/L GSH+25 μmol/L niacin (P1), 30 μmol/L GSH+25 μmol/L niacin (P2), and 100 μmol/L GSH+25 μmol/L niacin (P3). After 72h incubation, protein carbonyl content (PCC) and glucose reactive protein (GRP78) content were assessed using ELISA examinations. After two-week incubation, advanced glycation end products (AGEs) were also assessed and the expression of αβ crystalline was measured using Western blot examination. RESULTS: PCC and GRP78 levels in the co-treated groups were not significantly reduced compared to control (P>0.05). In contrast, there was a significant decrease of the AGEs levels in all groups co-treated with GSH and niacin when compared with the control group (P<0.05). In addition, the αβ crystalline expression increased after high dose glucose administration, but decreased in all groups co-treated with GSH and combinations of GSH and niacin. CONCLUSION: Combinations of GSH and niacin inhibit the aggregation of proteins and prevent glycation in hyperglycemic HLE cells. This study shows that this combination may play an active role in preventing diabetic cataract mainly from the AGEs pathway.

Abstract TP94: Mesenchymal Stromal Cells Behave Differently When Exposed to Medications Commonly Prescribed to Stroke Patients

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Nikunj Satani ◽  
Bing Yang ◽  
Duyen M Nghiem ◽  
Xiaopei Xi ◽  
Adrian P Gee ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
High Glucose ◽  
Fold Increase ◽  
Stroke Recovery ◽  
Stroke Patients ◽  
Healthy Humans ◽  
Tnf Α ◽  
High Concentrations ◽  
And Function

Background: As a promising investigational therapy for stroke recovery, mesenchymal stromal cells (MSCs) are in various stages of clinical trials. MSCs may promote recovery through cytokine release and immunomodulation. Stroke patients typically are treated with antiplatelets and medications for hypertension and hyperlipidemia. We explored the effect of commonly prescribed drugs at physiological concentrations on MSCs. Methods: Clinical grade bone marrow MSCs from healthy donor at passage 2 were thawed and re-suspended in serum free media. Monocytes (Mo) were isolated from peripheral blood of healthy humans. MSCs and Mo were cultured alone as well as in co-culture and exposed to simvastatin, atenolol, losartan, captopril, or aspirin. They were also exposed to high glucose (upto 40mM) to simulate hyperglycemia. At 24 hours of incubation, media was collected and TNF-α concentration was measured, as an index of immunomodulation of Mo by MSCs. Cell viability was also measured (using MTT assay and flow cytometry). Results: There were significant effects of all drugs on viability of MSCs but with no impact on Mo. More importantly, Losartan (dose independent), Simvastatin and Atenolol (dose-dependent) reduced the viability of MSCs even at the pharmacologically relevant concentrations (Fig 1). High glucose had no effect on viability of MSCs or Mo. TNF-α secretion from co-culture of MSCs and Mo at 24 hours showed differences at very high doses of aspirin (2-fold increase), atenolol (0.5 fold decrease), and glucose (0.5 fold decrease) (data not shown). However, these high concentrations are unlikely to be achieved pharmacologically in plasma of patients treated with these drugs. Conclusion: Exposure of MSCs to clinically relevant drugs can alter their viability and function. Our results suggest that stroke trials involving use of intravenous MSCs should consider the differential impact of commonly prescribed medications on MSCs function.

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