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Journal ArticleDOI: 10.1080/13813455.2019.1620288

Metformin protects red blood cells against rotenone induced oxidative stress and cytotoxicity.

04 Mar 2021-Archives of Physiology and Biochemistry (Arch Physiol Biochem)-Vol. 127, Iss: 2, pp 102-111
Abstract: The anti-diabetic medicine metformin has been reported as an anti-ageing drug candidate as it mimics the benefits of caloric restriction and reduces ageing-related oxidative stress in various exper...

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Topics: Oxidative stress (53%), Metformin (52%), Rotenone (51%)

7 results found

Open accessJournal ArticleDOI: 10.1016/J.REDOX.2020.101517
25 May 2020-Redox biology
Abstract: Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin is still not fully understood. This review provides an overview of the existing literature concerning the beneficial mitochondrial and vascular effects of metformin, which it exerts by diminishing oxidative stress and reducing leukocyte-endothelium interactions. Specifically, we describe the molecular mechanisms involved in metformin's effect on gluconeogenesis, its capacity to interfere with major metabolic pathways (AMPK and mTORC1), its action on mitochondria and its antioxidant effects. We also discuss potential targets for therapeutic intervention based on these molecular actions.

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Topics: Metformin (54%), Type 2 diabetes (51%)

29 Citations

Open accessJournal ArticleDOI: 10.3389/FNMOL.2020.00084
Abstract: Parkinson's disease (PD) is a neurodegenerative disease that affects substantia nigra dopamine neurons. Many studies have documented the role of oxidative stress and angiogenesis in the pathogenesis of PD. Metformin (MTF) is an antidiabetic medication and AMP-activated protein kinase (AMPK) regulator that has shown antioxidant and antiangiogenic properties in many disorders. The aim of this study is to investigate the neuroprotective effect of MTF in a mouse model of rotenone-prompted PD with a highlight on its influence on the AMPK/forkhead box transcription factor O3 (FOXO3) pathway and striatal angiogenesis. In the running study, PD was induced in mice using repeated doses of rotenone and concomitantly treated with MTF 100 or 200 mg/kg/day for 18 days. Rotarod and pole tests were used to examine the animals' motor functionality. After that, animals were sacrificed, and brains were isolated and processed for immunohistochemical investigations or biochemical analyses. Oxidant stress and angiogenic markers were measured, including reduced glutathione, malondialdehyde, the nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1, thioredoxin, AMPK, FOXO3, and vascular endothelial growth factor (VEGF). Results indicated that MTF improved animals' motor function, improved striatal glutathione, Nrf2, hemoxygenase-1, and thioredoxin. Furthermore, MTF upregulated AMPK-FOXO3 proteins and reduced VEGF and cleaved caspase 3. MTF also increased the number of tyrosine hydroxylase (TH)-stained neurons in the substantia nigra neurons and in striatal neuronal terminals. This study is the first to highlight that the neuroprotective role of MTF is mediated through activation of AMPK-FOXO3 signaling and inhibition of the proangiogenic factor, VEGF. Further studies are warranted to confirm this mechanism in other models of PD and neurodegenerative diseases.

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Topics: AMPK (60%), Neuroprotection (54%), Substantia nigra (53%) ... read more

16 Citations

Open accessJournal ArticleDOI: 10.3390/BIOMEDICINES9010003
22 Dec 2020-Biomedicines
Abstract: Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin's efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin's beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis.

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Topics: Metformin (57%), Endothelial dysfunction (55%), Type 2 diabetes (53%) ... read more

12 Citations

Journal ArticleDOI: 10.1080/01480545.2019.1658769
Abstract: Acetaminophen or N-acetyl-p-amino-phenol (APAP) is a drug which is available over-the-counter for fever and pain. Its overdosing causes oxidative stress and subsequent acute liver damage. In the pr...

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Topics: Acetaminophen (57%), Toxicity (53%), Oxidative stress (51%)

6 Citations

Journal ArticleDOI: 10.5530/IJPI.2021.1.20
Abstract: Background: Rotenone is one of the most widely used pesticides in agriculture and may affect public health through the food chain. A possible mechanism of rotenone toxicity is oxidative stress. This study, the supportive effect of crocin (a substance derived from saffron) as an antioxidant on the renal toxicity of rotenone in an experimental animal model was investigated. Methods: First, male rats were divided into 4 groups (6 in each group) and received saline, crocin, rotenone and rotenone-crocin combination intraperitoneally for 10 days, respectively. Blood and kidney tissue samples were then isolated and biochemical factors including creatinine, nitrogen blood urea (BUN), sodium, potassium, Malondialdehyde and catalase were measured. The kidneys were examined histopathologically with a light microscope. Results: The results showed that rotenone caused damage to kidney tissue, which was observed in the form of vacuole degeneration, hyperemia and influx of inflammatory cells. Crocin has also been shown to reduce the severity of rotenone-induced kidney damage. Also results showed that biochemical changes were not statistically significant between the groups. Conclusions: The crocin has protective influence on histopathological changes in rat᾽s kidney following rotenone administration.

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Topics: Crocin (58%), Rotenone (54%), Kidney (51%) ... read more

1 Citations


78 results found

Open accessJournal Article
Abstract: Since 1922 when Wu proposed the use of the Folin phenol reagent for the measurement of proteins, a number of modified analytical procedures utilizing this reagent have been reported for the determination of proteins in serum, in antigen-antibody precipitates, and in insulin. Although the reagent would seem to be recommended by its great sensitivity and the simplicity of procedure possible with its use, it has not found great favor for general biochemical purposes. In the belief that this reagent, nevertheless, has considerable merit for certain application, but that its peculiarities and limitations need to be understood for its fullest exploitation, it has been studied with regard to effects of variations in pH, time of reaction, and concentration of reactants, permissible levels of reagents commonly used in handling proteins, and interfering substances. Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.

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Topics: Reagent (61%), Sulfhydryl reagent (61%), Folin–Ciocalteu reagent (61%) ... read more

285,427 Citations

Open accessJournal ArticleDOI: 10.1016/S0021-9258(18)84756-1
Cyrus H. Fiske1, Y. Subbarow1Institutions (1)
Topics: Phosphorus (55%)

17,827 Citations

Journal ArticleDOI: 10.1006/ABIO.1996.0292
Abstract: A simple, automated test measuring the ferric reducing ability of plasma, the FRAP assay, is presented as a novel method for assessing "antioxidant power." Ferric to ferrous ion reduction at low pH causes a colored ferrous-tripyridyltriazine complex to form. FRAP values are obtained by comparing the absorbance change at 593 nm in test reaction mixtures with those containing ferrous ions in known concentration. Absorbance changes are linear over a wide concentration range with antioxidant mixtures, including plasma, and with solutions containing one antioxidant in purified form. There is no apparent interaction between antioxidants. Measured stoichiometric factors of Trolox, alpha-tocopherol, ascorbic acid, and uric acid are all 2.0; that of bilirubin is 4.0. Activity of albumin is very low. Within- and between-run CVs are <1.0 and <3.0%, respectively, at 100-1000 micromol/liter. FRAP values of fresh plasma of healthy Chinese adults: 612-1634 micromol/liter (mean, 1017; SD, 206; n = 141). The FRAP assay is inexpensive, reagents are simple to prepare, results are highly reproducible, and the procedure is straightforward and speedy. The FRAP assay offers a putative index of antioxidant, or reducing, potential of biological fluids within the technological reach of every laboratory and researcher interested in oxidative stress and its effects.

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14,843 Citations

Book ChapterDOI: 10.1016/0076-6879(90)86141-H
Abstract: Publisher Summary This chapter discusses methods to determine carbonyl content in oxidatively modified proteins. The methods described are (1) reduction of the carbonyl group to an alcohol with tritiated borohydride; (2) reaction of the carbonyl group with 2,4-dinitrophenylhydrazine to form the 2,4-dinitrophenylhydrazone; (3) reaction of the carbonyl with fluorescein thiosemicarbazide to form the thiosemicarbazone; and (4) reaction of the carbonyl group with fluorescein amine to form a Schiff base followed by reduction to the secondary amine with cyanoborohydride. Van Poelje and Snell have also quantitated protein-bound pyruvoyl groups through formation of a Schiff base with p-aminobenzoic acid followed by reduction with cyanoborohydride. Although a systematic investigation has not appeared, this method should also be useful in detecting other protein-bound carbonyl groups. Carbonyl content of proteins is expressed as moles carbonyl/mole subunit for purified proteins of known molecular weight. For extracts, the results may be given as nanomoles carbonyl/milligram protein. For a protein having a molecular weight of 50,000, a carbonyl content of 1 mol carbonyl/mol protein corresponds to 20 nmol carbonyl/mg proteins.

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Topics: Protein Carbonyl Content (78%), Protein Carbonylation (55%), Schiff base (52%) ... read more

5,074 Citations

Open accessJournal ArticleDOI: 10.1172/JCI13505
Gaochao Zhou1, Robert W. Myers1, Ying Li1, Yuli Chen1  +10 moreInstitutions (1)
Abstract: Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.

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Topics: AMPK (78%), AMP-activated protein kinase (60%), Glucose uptake (57%) ... read more

4,744 Citations