scholarly journals Pretreatment of Small-for-Size GraftsIn Vivobyγ-Aminobutyric Acid Receptor Regulation against Oxidative Stress-Induced Injury in Rat Split Orthotopic Liver Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Tomohide Hori ◽  
Shinji Uemoto ◽  
Lindsay B. Walden ◽  
Feng Chen ◽  
Ann-Marie T. Baine ◽  
...  

Background. Graft pretreatment to limit postoperative damage has the advantage of overcoming a current issue in liver transplantation (LT). The strategic potential of graft pretreatmentin vivoby a specific agonist forγ-aminobutyric acid receptor (GABAR) was investigated in the rat LT model with a small-for-size graft (SFSG).Methods. Recipient rats were divided into three groups according to donor treatments and recipient surgeries: (i) saline and laparotomy, (ii) saline and split orthotopic liver transplantation (SOLT) with 40%-SFSG, and (iii) GABAR agonist and SOLT with 40%-SFSG. Survival was evaluated. Blood and liver samples were collected 6 h after surgery. Immunohistological assessment for apoptotic induction and western blotting for 4-hydroxynonenal, ataxia-telangiectasia mutated kinase (ATM), histone H2AX, phosphatidylinositol-3 kinase (PI3K), Akt, and free radical scavenging enzymes were performed.Results. Pretreatment by GABAR showed improvement in survival, histopathological assessment, and biochemical tests. Apoptotic induction and oxidative stress were observed after SOLT with an SFSG, and this damage was limited by GABAR regulation. GABAR regulation appeared to reduce DNA damage via the ATM/H2AX pathway and to promote cell survival via the PI3K/Akt pathway.Conclusions. Pretreatmentin vivoby GABAR regulation improves graft damage after SOLT with an SFSG. This strategy may be advantageous in LT.

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 309
Author(s):  
Olukayode O. Aremu ◽  
Adebola O. Oyedeji ◽  
Opeoluwa O. Oyedeji ◽  
Benedicta N. Nkeh-Chungag ◽  
Constance R. Sewani Rusike

Oxidative stress has gained attention as one of the fundamental mechanisms responsible for the development of hypertension. The present study investigated in vitro and in vivo antioxidant effects of 70% ethanol-water (v/v) leaf and root extracts of T. officinale (TOL and TOR, respectively). Total phenolic and flavonoid content of plant extracts were assessed using Folin Ciocalteau and aluminium chloride colorimetric methods; while, 2,2-diphenyl-1-picrlhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) protocols were used to determine the free radical scavenging and total antioxidant capacities (TAC), respectively. The in vivo total antioxidant capacity and malondialdehyde acid (MDA) levels for lipid peroxidation tests were performed on organ homogenate samples from Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats treated with leaf extract, TOL (500 mg/kg/day) and TOR (500 mg/kg/day) for 21 days. Results showed that compared to TOR, TOL possessed significantly higher (p < 0.01) polyphenol (4.35 ± 0.15 compared to 1.14 ± 0.01) and flavonoid (23.17 ± 0.14 compared to 3 ± 0.05) content; free radical scavenging activity (EC50 0.37 compared to 1.34 mg/mL) and total antioxidant capacities (82.56% compared to 61.54% ABTS, and 156 ± 5.28 compared to 40 ± 0.31 FRAP) and both extracts showed no toxicity (LD50 > 5000 mg/kg). TOL and TOR significantly (p < 0.01) elevated TAC and reduced MDA levels in targets organs. In conclusion, T. officinale leaf extract possesses significant anti-oxidant effects which conferred significant in vivo antioxidant protection against free radical-mediated oxidative stress in L-NAME-induced hypertensive rats.


2015 ◽  
Vol 122 (1) ◽  
pp. 72-86 ◽  
Author(s):  
Chenfang Luo ◽  
Dongdong Yuan ◽  
Xiaoyun Li ◽  
Weifeng Yao ◽  
Gangjian Luo ◽  
...  

Abstract Background: Postliver transplantation acute kidney injury (AKI) severely affects patient survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion induced enhancement of connexin32 (Cx32) gap junction plays a critical role in mediating postliver transplantation AKI and that pretreatment/precondition with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. Methods: Male Sprague–Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx32 inhibitor, 2-aminoethoxydiphenyl borate or propofol (50 mg/kg) (n = 8 per group). Also, kidney tubular epithelial (NRK-52E) cells were subjected to hypoxia–reoxygenation and the function of Cx32 was manipulated by three distinct mechanisms: cell culture in different density; pretreatment with Cx32 inhibitors or enhancer; Cx32 gene knock-down (n = 4 to 5). Results: AOLT resulted in significant increases of renal Cx32 protein expression and gap junction, which were coincident with increases in oxidative stress and impairment in renal function and tissue injury as compared to sham group. Similarly, hypoxia–reoxygenation resulted in significant cellular injury manifested as reduced cell growth and increased lactate dehydrogenase release, which was significantly attenuated by Cx32 gene knock-down but exacerbated by Cx32 enhancement. Propofol inhibited Cx32 function and attenuated post-AOLT AKI. In NRK-52E cells, propofol reduced posthypoxic reactive oxygen species production and attenuated cellular injury, and the cellular protective effects of propofol were reinforced by Cx32 inhibition but cancelled by Cx32 enhancement. Conclusion: Cx32 plays a critical role in AOLT-induced AKI and that inhibition of Cx32 function may represent a new and major mechanism whereby propofol reduces oxidative stress and subsequently attenuates post-AOLT AKI.


2021 ◽  
Author(s):  
Arnold N. Onyango

Unhealthy diets, such as those high in saturated fat and sugar accelerate the development of non-communicable diseases. The metabolic syndrome is a conglomeration of disorders such as abdominal obesity, hypertension, impaired glucose regulation and dyslipidemia, which increases the risk for diabetes and cardiovascular disease. The prevalence of the metabolic syndrome is increasing globally, and dietary interventions may help to reverse this trend. A good understanding of its pathophysiological mechanisms is needed for the proper design of such interventions. This chapter discusses how lipid peroxidation is associated with the development of this syndrome, mainly through the formation of bioactive aldehydes, such as 4-hydroxy-2-nonenal, malondialdehyde, acrolein and glyoxal, which modify biomolecules to induce cellular dysfunction, including the enhancement of oxidative stress and inflammatory signaling. It gives a current understanding of the mechanisms of formation of these aldehydes and how dietary components such as saturated fatty acids promote oxidative stress, leading to lipid oxidation. It also outlines mechanisms, apart from free radical scavenging and singlet oxygen quenching, by which various dietary constituents prevent oxidative stress and lipid oxidation in vivo.


2017 ◽  
Author(s):  
Nicola J. Drummond ◽  
Nick O. Davies ◽  
Janet E. Lovett ◽  
Mark R. Miller ◽  
Graeme Cook ◽  
...  

AbstractExcessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.


Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1565 ◽  
Author(s):  
Turin-Moleavin ◽  
Fifere ◽  
Lungoci ◽  
Rosca ◽  
Coroaba ◽  
...  

Background. Cerium oxide nanoparticles present the mimetic activity of superoxide dismutase, being able to inactivate the excess of reactive oxygen species (ROS) correlated with a large number of pathologies, such as stents restenosis and the occurrence of genetic mutations that can cause cancer. This study presents the synthesis and biological characterisation of nanoconjugates based on nanoparticles of iron oxide interconnected with cerium oxide conjugates. Methods. The synthesis of magnetite-nanoceria nanoconjugates has been done in several stages, where the key to the process is the coating of nanoparticles with polyethyleneimine and its chemical activation-reticulation with glutaraldehyde. The nanoconjugates are characterised by several techniques, and the antioxidant activity was evaluated in vitro and in vivo. Results. Iron oxide nanoparticles interconnected with cerium oxide nanoparticles were obtained, having an average diameter of 8 nm. Nanoconjugates prove to possess superparamagnetic properties and the saturation magnetisation varies with the addition of diamagnetic components in the system, remaining within the limits of biomedical applications. In vitro free-radical scavenging properties of nanoceria are improved after the coating of nanoparticles with polyethylenimine and conjugation with magnetite nanoparticles. In vivo studies reveal increased antioxidant activity in all organs and fluids collected from mice, which demonstrates the ability of the nanoconjugates to reduce oxidative stress. Conclusion. Nanoconjugates possess magnetic properties, being able to scavenge free radicals, reducing the oxidative stress. The combination of the two properties mentioned above makes them excellent candidates for theranostic applications.


Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1435 ◽  
Author(s):  
Stella Maria Andrade Gomes Barreto ◽  
Cesar Orlando Muñoz Cadavid ◽  
Rafael Amir de Oliveira Moura ◽  
Giovanna Melo Martins Silva ◽  
Samara Vitória Ferreira de Araújo ◽  
...  

Agave sisalana agro-industrial residue has considerable potential against damage associated with oxidative stress and skin aging. This study aims to demonstrate, in vitro and in vivo, the potential of Agave sisalana agro-industrial residue as a safe and effective alternative for the prevention of damage caused by oxidative stress and aging. The antioxidant activity was evaluated in vitro (total antioxidant capacity, reducing power, DPPH radical scavenging, metal chelating (Fe2+ and Cu2+), and hydroxyl radical scavenging) and in vivo using the Caenorhabditis elegans organism model. The extract showed in vitro antioxidant activity in all tests performed. Tests with C. elegans showed that the extract was able to reduce the intracellular levels of reactive oxygen species (ROS) and increase the survival rate of worms. A downregulation of gst-4::GFP expression suggests a direct action against free radicals. Agave sisalana agro-industrial residue extract (AsRE) can therefore be considered as a source of antioxidant biomolecules, and the use of this agro-industrial residue in a new production process can lead to sustainability and socioeconomic development.


Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1106
Author(s):  
Natasha Rios Leite ◽  
Laura Costa Alves de Araújo ◽  
Paola dos Santos da Rocha ◽  
Danielle Araujo Agarrayua ◽  
Daiana Silva Ávila ◽  
...  

Fruits are sources of bioactive compounds that are responsible for several biological activities. Therefore, this study aimed to identify the chemical composition of the pulp of the Brazilian Savanna fruit Dipteryx alata; evaluate its toxic effects, influence on the life expectancy of the nematode Caenorhabditis elegans, and its antioxidant activities in vitro and in vivo; and describe the mechanisms involved. The chemical compounds identified include phenols, terpenes, fatty acid derivatives, vitamins, and a carboxylic acid. The in vitro antioxidant activity was demonstrated by radical scavenging methods. in vivo, the D. alata fruit pulp was not toxic and promoted resistance to oxidative stress in nematodes exposed to a chemical oxidizing agent. Furthermore, it promoted an increased life expectancy in wild-type nematodes and increased the expression of superoxide dismutase and the nuclear translocation of DAF-16. These results suggest that the beneficial effects identified are related to these two genes, which are involved in the regulation of metabolic activities, the control of oxidative stress, and the lifespan of C. elegans. These beneficial effects, which may be related to its chemical constituents, demonstrate its potential use as a functional and/or nutraceutical food.


2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Amanda C. Okolie ◽  
Oluwafemi E. Kale ◽  
Odutola Osilesi

AbstractRecent studies have shown that Type 2 diabetes (T2D) in rats can result through a synergy that links obesity to insulin resistance and β-cell dysfunction. The present study achieved T2D via high fructose (20%w/v, p.o.), streptozotocin single dose (40 mg/kg, i.p.) (HFSTZ) in rats. Also, chemoprotective potential of butanol fraction of Buchholzia coriacea (BFBC) was demonstrated. Control normal and diabetic untreated (HFSTZ-induced T2D) rats received CM-cellulose (1 mg/kg, p.o.). Diabetic rats received intragastric BFBC (20, 200, 400 mg/kg), glibenclamide (0.07 mg/kg), and BFBC (200 mg/kg) plus glibenclamide treatments, respectively. 2,2-Diphenyl-1-picrylhydrazyl, nitric oxide radical, hydroxyl radical scavenging activities, and α-amylase inhibition were assessed. After 2 weeks of treatments, blood glucose levels, lipid profiles, renal and liver function, serum insulin as well as in vivo oxidative stress biomarkers were assessed. BFBC shows highest antioxidants and α-amylase inhibitory activities in vitro. HFSTZ-induced T2D produced hyperglycemia (P<0.05–0.001; F = 5.26–26.47), serum hyperinsulinemia (six-folds) plus elevated lipid peroxidation levels. Similarly, there were altered lipid profiles, liver and renal biomarker enzymes plus weight loss. BFBC administration alone or in combination with glibenclamide reversed T2D symptomatologies in treated animals, and improved body weights against control diabetic rats. In vivo antioxidant activities also improved while histological sections in treated rats show reduced tissue damage in pancreas, kidneys, liver, and heart, respectively. Oleic, stearic, 2-methyl-pyrrolidine-2-carboxylic, and n-hexadecanoic acids were present in BFBC in large quantities given GC-MS analysis. Overall, data from the present study suggest chemoprotective potentials of BFBC against HFSTZ-induced T2D rats.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
TM Archana ◽  
K Soumya ◽  
Jesna James ◽  
Sudheesh Sudhakaran

Abstract Background Hyperglycemia is the hallmark of diabetes, and the associated oxidative stress is a major concern that invites an array of diabetic complications. The traditional practices of medicare are of great, current interest due to the high cost and side effects of conventional diabetic medications. The present in vitro study focuses on evaluating the potential of various A. occidentale root extracts for their antihyperglycemic and antioxidant potentials. Materials and methods The four different solvent extracts petroleum ether (PEAO), chloroform (CHAO), ethyl acetate (EAAO), and 80 % methanol (80 % MAO) of A. occidentale roots were evaluated for their total phenolic, flavonoid, and antioxidant capacity. Using MIN6 pancreatic β-cells, the cytotoxicity of the extracts was evaluated by MTT assay and the antidiabetic potential by quantifying the insulin levels by ELISA at a higher concentration of glucose. The effect of 80 % MAO on INS gene expression was determined by qRT PCR analysis. Results Among the four different solvent extracts of A. occidentale roots, 80 % MAO showed the highest concentration of phenolics (437.33 ± 0.03 µg GAE/mg), CHAO to be a rich source of flavonoids (46.04 ± 0.1 µg QE/mg) and with the highest total antioxidant capacity (1865.33 ± 0.09 µg AAE/ mg). Evaluation of the free radical scavenging and reducing properties of the extracts indicated 80 % MAO to exhibit the highest activity. The MTT assay revealed the least cytotoxicity of all four extracts. 80 % MAO enhanced INS up-regulation as well as insulin secretion even under high glucose concentration (27mM). Conclusions The present study demonstrated that the A. occidentale root extracts have effective antihyperglycemic and antioxidative properties, together with the potential of normalizing the insulin secretory system of β-cells. Above mentioned properties have to be studied further by identifying the active principles of A. occidentale root extracts and in vivo effects. The prospect of the present study is identifying drug leads for better management of diabetes from the A. occidentale root extracts. Graphical abstract


ChemPlusChem ◽  
2014 ◽  
Vol 79 (8) ◽  
pp. 1083-1088 ◽  
Author(s):  
Uschi M. Graham ◽  
Michael T. Tseng ◽  
Jacek B. Jasinski ◽  
Robert A. Yokel ◽  
Jason M. Unrine ◽  
...  

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