scholarly journals Can Diabetes I and Early Blindness Be Prevented Using a Tylenol Combination Which Inhibits Oxidative and Nitrosative Stress?

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Knox Van Dyke ◽  
Erica Ghareeb ◽  
Robert Hoeldtke ◽  
Mark Van Dyke ◽  
Chris Van Dyke ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Beta Cell ◽  
Nitrosative Stress ◽  
Pancreatic Beta Cell ◽  
Blood Glucose Control ◽  
Scientific Basis ◽  
Oxidative And Nitrosative Stress ◽  
Insulin Synthesis ◽  
Dinitrogen Tetraoxide

Since oxidative/nitrosative stress cause diabetes, can we prevent this chemistry generating the disease? Streptozotocin causes diabetes by entering the pancreatic beta cell generating excessive nitric oxide which reacts with oxygen creating a toxin possibly peroxynitrite, dinitrogen trioxide, dinitrogen tetraoxide and so forth. The toxic compounds damage the DNA causing beta cell death. This prevents insulin synthesis, storage and release. By using antioxidant substances that destroy the nitric-oxide-based toxins (e.g., carboxy-PTIO (oxidizes nitric oxide), polyphenolic-quercetin and monophenolic acetaminophen (Tylenol)) which are oxidation and nitration targets can the diabetes I causing toxins in animals be destroyed? Will this tri-drug combination completely prevent the deleterious effects of diabetes namely poor blood glucose control and blindness from cataracts for the entire length of the experiment (one year). These disease reversal experiments were accomplished in rats where the streptozotocin-diabetic effects were completely thwarted. In vitro experiments were accomplished to provide the scientific basis for the experimental results in animals.

scholarly journals Hepatoprotective Effect of the Ethanol Extract of Illicium henryi against Acute Liver Injury in Mice Induced by Lipopolysaccharide

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 446 ◽  
Author(s):  
Islam ◽  
Yu ◽  
Miao ◽  
Liu ◽  
He ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Nitrosative Stress ◽  
Acute Liver Injury ◽  
Ethanol Extract ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Oxidative And Nitrosative Stress ◽  
Stress Burden

The root bark of Illicium henryi has been used in traditional Chinese medicine to treat lumbar muscle strain and rheumatic pain. Its ethanol extract (EEIH) has been previously reported to attenuate lipopolysaccharide (LPS)-induced acute kidney injury in mice. The present study aimed to evaluate the in vitro antioxidant activities and in vivo protective effects of EEIH against LPS-induced acute liver injury (ALI) in mice as well as explore its molecular mechanisms. The mice were injected intraperitoneally (i.p.) with EEIH at the doses of 1.25, 2.5, and 5.0 mg/kg every day for 5 days. One hour after the last administration, the mice were administered i.p. with LPS (8 mg/kg). After fasting for 12 h, blood and liver tissues were collected to histopathological observation, biochemical assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analyses. EEIH possessed 2,2-diphenyl-1-picrylhydrazil (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiozoline-6-sulfonic acid) disodium salt (ABTS) radical scavenging activities and ferric-reducing antioxidant capacity in vitro. The histopathological examination, serum biochemical analysis, and liver myeloperoxidase (MPO) activity showed that EEIH pretreatment alleviated LPS-induced liver injury in mice. EEIH significantly dose-dependently decreased the mRNA and protein expression levels of inflammatory factors TNF-α, IL-1β, IL-6, and COX-2 in liver tissue of LPS-induced ALI mice via downregulating the mRNA and protein expressions of toll-like receptor 4 (TLR4) and inhibiting the phosphorylation of nuclear factor-κB (NF-κB) p65. Furthermore, EEIH markedly ameliorated liver oxidative and nitrosative stress burden in LPS-treated mice through reducing the content of thiobarbituric acid reactive substances (TBARS), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) levels, restoring the decreased superoxide dismutase (SOD) and reduced glutathione (GSH) levels, and up-regulating nuclear factor erythroid 2 related factor 2 (Nrf2). These results demonstrate that EEIH has protective effects against ALI in mice via alleviating inflammatory response, oxidative and nitrosative stress burden through activating the Nrf2 and suppressing the TLR4/NF-κB signaling pathways. The hepatoprotective activity of EEIH might be attributed to the flavonoid compounds such as catechin (1), 3′,4′,7-trihydroxyflavone (2), and taxifolin (7) that most possibly act synergistically.

scholarly journals What Is the Metabolic Amplification of Insulin Secretion and Is It (Still) Relevant?

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 355
Author(s):  
Ingo Rustenbeck ◽  
Torben Schulze ◽  
Mai Morsi ◽  
Mohammed Alshafei ◽  
Uwe Panten
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Adenine Nucleotides ◽  
Pancreatic Beta Cell ◽  
Secretory Response ◽  
Mitochondrial Activity ◽  
Insulin Synthesis ◽  
Sequence Of Events ◽  
Insulin Granules

The pancreatic beta-cell transduces the availability of nutrients into the secretion of insulin. While this process is extensively modified by hormones and neurotransmitters, it is the availability of nutrients, above all glucose, which sets the process of insulin synthesis and secretion in motion. The central role of the mitochondria in this process was identified decades ago, but how changes in mitochondrial activity are coupled to the exocytosis of insulin granules is still incompletely understood. The identification of ATP-sensitive K+-channels provided the link between the level of adenine nucleotides and the electrical activity of the beta cell, but the depolarization-induced Ca2+-influx into the beta cells, although necessary for stimulated secretion, is not sufficient to generate the secretion pattern as produced by glucose and other nutrient secretagogues. The metabolic amplification of insulin secretion is thus the sequence of events that enables the secretory response to a nutrient secretagogue to exceed the secretory response to a purely depolarizing stimulus and is thus of prime importance. Since the cataplerotic export of mitochondrial metabolites is involved in this signaling, an orienting overview on the topic of nutrient secretagogues beyond glucose is included. Their judicious use may help to define better the nature of the signals and their mechanism of action.

scholarly journals A Possible Novel Anti-Inflammatory Mechanism for the Pharmacological Prolyl Hydroxylase Inhibitor 3,4-Dihydroxybenzoate: Implications for Use as a Therapeutic for Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Shankar J. Chinta ◽  
Subramanian Rajagopalan ◽  
Abirami Ganesan ◽  
Julie K. Andersen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microglial Activation ◽  
Nitrosative Stress ◽  
Neurodegenerative Disorder ◽  
Oxidative And Nitrosative Stress ◽  
Prolyl Hydroxylases ◽  
Age Related

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized in part by the preferential loss of nigrostriatal dopaminergic neurons. Although the precise etiology of PD is unknown, accumulating evidence suggests that PD involves microglial activation that exerts neurotoxic effects through production of proinflammatory cytokines and increased oxidative and nitrosative stress. Thus, controlling microglial activation has been suggested as a therapeutic target for combating PD. Previously we demonstrated that pharmacological inhibition of a class of enzymes known as prolyl hydroxylases via 3,4-dihydroxybenzoate administration protected against MPTP-induced neurotoxicity, however the exact mechanisms involved were not elucidated. Here we show that this may be due to DHB’s ability to inhibit microglial activation. DHB significantly attenuated LPS-mediated induction of nitric oxide synthase and pro-inflammatory cytokines in murine BV2 microglial cellsin vitroin conjunction with reduced ROS production and activation of NFκB and MAPK pathways possibly due to up-regulation of HO-1 levels. HO-1 inhibition partially abrogates LPS-mediated NFκB activity and subsequent NO induction.In vivo, DHB pre-treatment suppresses microglial activation elicited by MPTP treatment. Our results suggest that DHB’s neuroprotective properties could be due to its ability to dampen induction of microglial activation via induction of HO-1.

scholarly journals Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase

Gut ◽  
1999 ◽  
Vol 45 (2) ◽  
pp. 199-209 ◽  
Author(s):  
B Zingarelli ◽  
C Szabó ◽  
A L Salzman
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Experimental Colitis ◽  
Neutrophil Infiltration ◽  
Intercellular Adhesion Molecule ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Oxidative And Nitrosative Stress ◽  
Intense Staining ◽  
Genetic Ablation

BACKGROUNDOxidative and nitrosative stress have been implicated in the pathogenesis of inflammatory bowel diseases.AIMSTo study the role of nitric oxide (NO) derived from inducible NO synthase (iNOS) in an experimental model of murine enterocolitis.METHODSTrinitrobenzene sulphonic acid (TNBS) was instilled per rectum to induce a lethal colitis in iNOS deficient mice and in wild type controls. The distal colon was evaluated for histological evidence of inflammation, iNOS expression and activity, tyrosine nitration and malondialdehyde formation (as indexes of nitrosative and oxidative stress), myeloperoxidase activity (as index of neutrophil infiltration), and tissue localisation of intercellular adhesion molecule 1 (ICAM-1).RESULTSTNBS administration induced a high mortality and weight loss associated with a severe colonic mucosal erosion and ulceration, increased myeloperoxidase activity, increased concentrations of malondialdehyde, and an intense staining for nitrotyrosine and ICAM-1 in wild type mice. Genetic ablation of iNOS gene conferred to mice a significant resistance to TNBS induced lethality and colonic damage, and notably reduced nitrotyrosine formation and concentrations of malondialdehyde; it did not, however, affect neutrophil infiltration and intestinal ICAM-1 expression in the injured tissue.CONCLUSIONData show that activation of iNOS is required for nitrosative and oxidative damage in experimental colitis.

Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats

2007 ◽  
Vol 293 (5) ◽  
pp. F1691-F1698 ◽  
Author(s):  
Cristino Cruz ◽  
Ricardo Correa-Rotter ◽  
Dolores Javier Sánchez-González ◽  
Rogelio Hernández-Pando ◽  
Perla D. Maldonado ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Renal Damage ◽  
Nitrosative Stress ◽  
Antioxidant Properties ◽  
Oxidative And Nitrosative Stress ◽  
Nitric Oxide Synthase 3 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Progressive renal damage and hypertension are associated with oxidative and nitrosative stress. On the other hand, S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract (AG), has antioxidant properties. The effects of SAC and AG on blood pressure, renal damage, and oxidative and nitrosative stress were studied in five-sixths nephrectomized rats treated with SAC (200 mg/kg ip) and AG (1.2 ml/kg ip) every other day for 30 days. Proteinuria and serum creatinine and blood urea nitrogen concentrations were measured on days 0, 5, 10, 15, and 30, and systolic blood pressure was recorded on days 0, 15, and 30. The degree of glomerulosclerosis and tubulointerstitial damage, the immunostaining for inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), and the subunits of NADPH oxidase p22phox and gp91phox, and the activity of SOD were determined on day 30. SAC and AG reduced hypertension, renal damage, and the abundance of inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), p22phox, and gp91phox and increased SOD activity. Our data suggest that the antihypertensive and renoprotective effects of SAC and AG are associated with their antioxidant properties and that they may be used to ameliorate hypertension and delay the progression of renal damage.

scholarly journals Roles of Nitric Oxide and Prostaglandins in the Sustained Antihypertensive Effects of Acanthospermum hispidum DC. on Ovariectomized Rats with Renovascular Hypertension

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Rhanany Alan Calloi Palozi ◽  
Maysa Isernhagen Schaedler ◽  
Cleide Adriane Signor Tirloni ◽  
Aniely Oliveira Silva ◽  
Francislaine Aparecida dos Reis Lívero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renovascular Hypertension ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Folk Medicine ◽  
Thiobarbituric Acid ◽  
Ovariectomized Rats ◽  
Oxidative And Nitrosative Stress ◽  
Antihypertensive Response

Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery. Enalapril (15 mg/kg) and hydrochlorothiazide (25 mg/kg) were used as standard drugs. Diuretic activity was evaluated on days 1, 7, 14, 21, and 28. Systolic, diastolic, and mean blood pressure and heart rate were recorded. Serum creatinine, urea, thiobarbituric acid reactive substances, nitrosamine, nitrite, aldosterone, vasopressin levels, and ACE activity were measured. The vascular reactivity and the role of nitric oxide (NO) and prostaglandins (PG) in the vasodilator response of ESAH on the mesenteric vascular bed (MVB) were also investigated. ESAH treatment induced an important saluretic and antihypertensive response, therefore recovering vascular reactivity in 2K1C plus OVT-rats. This effect was associated with a reduction of oxidative and nitrosative stress with a possible increase in the NO bioavailability. Additionally, a NO and PG-dependent vasodilator effect was observed on the MEV.

scholarly journals Differential regulation of metabolism by nitric oxide andS-nitrosothiols in endothelial cells

2011 ◽  
Vol 301 (3) ◽  
pp. H803-H812 ◽  
Author(s):  
Anne R. Diers ◽  
Katarzyna A. Broniowska ◽  
Victor M. Darley-Usmar ◽  
Neil Hogg
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Nitrosative Stress ◽  
Surrogate Marker ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor

S-nitrosation of thiols in key proteins in cell signaling pathways is thought to be an important contributor to nitric oxide (NO)-dependent control of vascular (patho)physiology. Multiple metabolic enzymes are targets of both NO and S-nitrosation, including those involved in glycolysis and oxidative phosphorylation. Thus it is important to understand how these metabolic pathways are integrated by NO-dependent mechanisms. Here, we compared the effects of NO and S-nitrosation on both glycolysis and oxidative phosphorylation in bovine aortic endothelial cells using extracellular flux technology to determine common and unique points of regulation. The compound S-nitroso-l-cysteine (l-CysNO) was used to initiate intracellular S-nitrosation since it is transported into cells and results in stable S-nitrosation in vitro. Its effects were compared with the NO donor DetaNONOate (DetaNO). DetaNO treatment caused only a decrease in the reserve respiratory capacity; however, l-CysNO impaired both this parameter and basal respiration in a concentration-dependent manner. In addition, DetaNO stimulated extracellular acidification rate (ECAR), a surrogate marker of glycolysis, whereas l-CysNO stimulated ECAR at low concentrations and inhibited it at higher concentrations. Moreover, a temporal relationship between NO- and S-nitrosation-mediated effects on metabolism was identified, whereby NO caused a rapid impairment in mitochondrial function, which was eventually overwhelmed by S-nitrosation-dependent processes. Taken together, these results suggest that severe pharmacological nitrosative stress may differentially regulate metabolic pathways through both intracellular S-nitrosation and NO-dependent mechanisms. Moreover, these data provide insight into the role of NO and related compounds in vascular (patho)physiology.

Nitric oxide and neuronal and pancreatic beta cell death

Toxicology ◽  
2000 ◽  
Vol 153 (1-3) ◽  
pp. 143-156 ◽  
Author(s):  
E Adeghate ◽  
S.H Parvez
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Beta Cell Death
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