scholarly journals Development of a caffeic acid–phthalimide hybrid compound for NADPH oxidase inhibition

RSC Advances ◽  
2021 ◽  
Vol 11 (29) ◽  
pp. 17880-17890
Author(s):  
Willian Henrique dos Santos ◽  
Maurício Ikeda Yoguim ◽  
Regina Gomes Daré ◽  
Luiz Carlos da Silva-Filho ◽  
Sueli Oliveira Silva Lautenschlager ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Caffeic Acid ◽  
Oxidase Inhibitor ◽  
Hybrid Compound ◽  
Nadph Oxidase Inhibitor ◽  
Oxidase Inhibition ◽  
Nadph Oxidase Inhibition

The incorporation of the phthalimide moiety into caffeic acid was decisive for its effectiveness as an NADPH oxidase inhibitor.

The effect of cadaverine on redox homeostasis of wheat seedling roots and their resistance to damage heating

2021 ◽  
pp. 116-137
Author(s):  
Alexandr I. Kokorev ◽  
◽  
Yuriy E. Kolupaev ◽  
Maxim A. Shkliarevskyi ◽  
Anna A. Lugovaya ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Antioxidant Enzymes ◽  
Nadph Oxidase ◽  
Diamine Oxidase ◽  
Oxidase Inhibitor ◽  
Guaiacol Peroxidase ◽  
Sod Activity ◽  
Wheat Seedlings ◽  
Nadph Oxidase Inhibitor ◽  
Survival Of Seedlings

Polyamines are plant metabolites involved in many processes under physiologically normal and stressful conditions. Cadaverine is one of the least studied plant polyamines. The relationship between its physiological effects and the formation of signaling mediators, in particular, reactive oxygen species (ROS), has hardly been specially studied. The aim of this work was to study the possible protective effect of cadaverine on wheat (Triticum aestivum L.) seedlings under heat stress and its relationship with the formation and detoxification of ROS by antioxidant enzymes. Etiolated seedlings of soft winter wheat variety Doskonala were used in the work. We treated three-day-old seedlings with cadaverine at concentrations ranging from 0.05 to 2.5 mM by adding it to the root incubation medium. In some variants of the experiment, we treated seedlings with a hydrogen peroxide scavenger dimethylthiourea (DMTU - 150 μM), a diamine oxidase inhibitor aminogunidine (1 mM) or an inhibitor NADPH oxidase imidazole (10 μM), as well as the indicated inhibitors in combination with cadaverine. The hydrogen peroxide content and the activity of antioxidant enzymes were determined in the roots of seedlings a certain time after treatment with the studied compounds. One day after the treatment of seedlings with cadaverine, ROS antagonists, and a combination of effectors, the seedlings were subjected to damaging heating in a water thermostat (10 min at 45 °C). 24 h after heating, we assessed the content of the products of lipid peroxidation (LPO) in the roots and, after 3 days, the survival of seedlings. Incubation in the presence of cadaverine increased the resistance of seedlings to damaging heat (See Fig. 1). The highest relative number of surviving seedlings was observed in the variant with 1 mM cadaverine treatment. Under the effect of cadaverine, the content of hydrogen peroxide in the roots increased (See Fig. 2). We observed a noticeable effect 1-4 h after the start of treatment, with a maximum after 2 h. Treatment of seedlings with a scavenger of hydrogen peroxide DMTU removed the manifestation of the effect of an increase in the content of H2 O2 in the roots caused by the action of cadaverine (See Fig. 3). This effect was also completely eliminated by the diamine oxidase inhibitor aminoguanidine and was almost unchanged in the presence of the NADPH oxidase inhibitor imidazole. The effect of heat stress on seedlings caused an increase in the content of the LPO products in them. Treatment with cadaverine markedly reduced this manifestation of oxidative stress. The antioxidant DMTU and the diamine oxidase inhibitor aminoguanidine largely neutralized the protective effect of cadaverine (See Fig. 4a). At the same time, the NADPH oxidase inhibitor imidazole had almost no effect on the manifestation of the effect of cadaverine on the LPO products content in roots. Under the influence of DMTU and aminoguanidine, but not imidazole, the positive effect of cadaverine on the survival of seedlings after damaging heating was also leveled out (See Fig. 4b). The treatment of seedlings with cadaverine caused a change in the activity of antioxidant enzymes in the roots (superoxide dismutase - SOD, catalase, and guaiacol peroxidase) (See Fig. 5). DMTU and aminoguanidine neutralized the effect of cadaverine-induced increase in the activity of catalase and guaiacol peroxidase, but had almost no effect on the increase in SOD activity in roots induced by this diamine (See Fig. 6). The NADPH oxidase inhibitor imidazole did not significantly affect the manifestation of the effect of increasing the activity of antioxidant enzymes when seedlings are treated with cadaverine. We can conclude that one of the signaling mediators involved in the regulation activity of catalase and guaiacol peroxidase and in the induction of heat resistance of wheat seedlings by exogenous cadaverine is hydrogen peroxide, which is formed during the oxidation of cadaverine by diamine oxidase. At the same time, the modification of SOD activity in the roots of wheat seedlings with cadaverine, apparently, can occur without the participation of ROS.

The NADPH oxidase inhibitor apocynin induces nitric oxide synthesis via oxidative stress

2008 ◽  
Vol 228 (3) ◽  
pp. 277-285 ◽  
Author(s):  
Chiara Riganti ◽  
Costanzo Costamagna ◽  
Sophie Doublier ◽  
Erica Miraglia ◽  
Manuela Polimeni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Oxidase Inhibitor ◽  
Nitric Oxide Synthesis ◽  
Nadph Oxidase Inhibitor

Towards specific NADPH oxidase inhibition by small synthetic peptides

2012 ◽  
Vol 69 (14) ◽  
pp. 2307-2314 ◽  
Author(s):  
Jamel El-Benna ◽  
Pham My-Chan Dang ◽  
Axel Périanin
Keyword(s):  
Nadph Oxidase ◽  
Synthetic Peptides ◽  
Oxidase Inhibition ◽  
Nadph Oxidase Inhibition

scholarly journals NADPH oxidase inhibitor inhibits methylglyoxal‐induced podocyte apoptosis (LB729)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Young Sook Kim ◽  
Dong Ho Jung ◽  
Bo‐Jeong Pyun ◽  
So‐Jin Choi Choi ◽  
Jin Sook Kim Kim
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Inhibitor ◽  
Nadph Oxidase Inhibitor

Abstract 38: Reactive Oxygen Species Contribute To Aneurysmal Rupture in Mice

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kenji Shimada ◽  
Yoshiteru Tada ◽  
Kosuke Wada ◽  
Mari Kudo ◽  
Shoko Murakami ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Xanthine Oxidase ◽  
Intracranial Aneurysms ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Gelatinase Activity ◽  
Xanthine Oxidase Inhibitor ◽  
Aneurysmal Rupture ◽  
Nadph Oxidase Inhibitor ◽  
Superoxide Scavenger

Background and Purpose: Inflammation and apoptosis are recognized as key factors for aneurysmal rupture. Reactive oxygen species (ROS) mediates both inflammation and apoptosis in vascular walls. Therefore, we hypothesized that ROS produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture. Recently we have demonstrated the feasibility of using a mouse model of intracranial aneurysms to test pharmacological therapies for the prevention of aneurysmal rupture. We tested the hypothesis by using this newly established mouse model. Methods: Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle (n=27), a superoxide scavenger (tempol; n=13), a xanthine oxidase inhibitor (oxypurinol; n=15), and a NADPH oxidase inhibitor (apocynin; n=16). Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. Dihydroethidium staining and in situ zymography were performed to detect superoxide production and gelatinase activity, respectively. Results: A superoxide scavenger (tempol) significantly reduced rupture rate (vehicle vs. tempol: 74% vs. 27%, P < 0.05) (Figure1). It reduced superoxide production and gelatinase activity in aneurysmal walls (Figure2). Furthermore, the xanthine oxidase inhibitor (oxypurinol), and the NADPH oxidase inhibitor (apocynin) reduced the rupture rate (vehicle vs. oxypurinol: 74% vs. 30%, P< 0.05, vehicle vs. apocynin: 74% vs. 33%, P < 0.05). Conclusion: Our results indicate that superoxide produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture, by activating matrix metalloproteinases.

Possible usefulness of apocynin, an NADPH oxidase inhibitor, for nitrate tolerance: prevention of NO donor-induced endothelial cell abnormalities

2007 ◽  
Vol 293 (1) ◽  
pp. H790-H797 ◽  
Author(s):  
Akiko Fukatsu ◽  
Toshio Hayashi ◽  
Asaka Miyazaki-Akita ◽  
Hisako Matsui-Hirai ◽  
Yukie Furutate ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Nadph Oxidase ◽  
Oxidase Inhibitor ◽  
Nitrate Tolerance ◽  
Tolerance Development ◽  
No Donor ◽  
Nadph Oxidase Inhibitor ◽  
Free Interval

The long-term benefits of nitroglycerin therapy are limited by tolerance development. Understanding the precise nature of mechanisms underlying nitroglycerin-induced endothelial cell dysfunction may provide new strategies to prevent tolerance development. In this line, we tested interventions to prevent endothelial dysfunction in the setting of nitrate tolerance. When bovine aortic endothelial cells (BAECs) were continuously treated with nitric oxide (NO) donors, including nitroglycerin, over 2–3 days, basal production of nitrite and nitrate (NOx) was diminished. The diminished basal NOx levels were mitigated by intermittent treatment allowing an 8-h daily nitrate-free interval during the 2- to 3-day treatment period. Addition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin restored the basal levels of NOx that were decreased by continuous nitroglycerin treatment of BAECs. Apocynin caused significant improvement of increased mRNA and protein levels of endothelial nitric oxide synthase (eNOS) in BAECs given nitroglycerin continuously over the treatment period. Apocynin also reduced endothelial production of reactive oxygen species (ROS) after continuous nitroglycerin treatment. These results showed an essential similarity to the effects of a nitrate-free interval. Application of the NOS inhibitor Nω-nitro- l-arginine methyl ester caused a recovery effect on basal NOx and eNOS expression but was without effect on ROS levels in continuously NO donor-treated BAECs. In conclusion, the present study characterized abnormal features and functions of endothelial cells following continuous NO donor application. We suggest that inhibition of NADPH oxidase, by preventing NO donor-induced endothelial dysfunction, may represent a potential therapeutic strategy that confers protection from nitrate tolerance development.

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