Reduction of nitrosative stress by methane: Neuroprotection through xanthine oxidoreductase inhibition in a rat model of mesenteric ischemia-reperfusion

Poles, Marietta Zita; Bódi, Nikolett; Bagyánszki, Mária; Fekete, Éva; Mészáros, András; Varga, Gabriella; Szücs, S; Nászai, Anna; Kiss, Liliána; Kozlov, Andrey V.; Boros, Mihály; Kaszaki, József

doi:10.1016/j.freeradbiomed.2018.03.024

Cited by 14 publications

(16 citation statements)

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“…Further in vitro and in vivo experimental data established that CH 4 exposure can influence the activity of xanthine oxidoreductase (XOR) as well (Boros et al, 2012; Poles et al, 2018). XOR is a major enzymatic source of reperfusion-induced superoxide formation, and catalyze the reduction of nitrite to nitric oxide (NO) under hypoxic conditions in a pH-, nitrite-, and O 2 -dependent manner.…”

Section: Anti-inflammatory and Anti-apoptotic Effects During Ischemiamentioning

confidence: 99%

Methane Production and Bioactivity-A Link to Oxido-Reductive Stress

Boros

Keppler

2019

Front. Physiol.

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Biological methane formation is associated with anoxic environments and the activity of anaerobic prokaryotes (Archaea). However, recent studies have confirmed methane release from eukaryotes, including plants, fungi, and animals, even in the absence of microbes and in the presence of oxygen. Furthermore, it was found that aerobic methane emission in plants is stimulated by a variety of environmental stress factors, leading to reactive oxygen species (ROS) generation. Further research presented evidence that molecules with sulfur and nitrogen bonded methyl groups such as methionine or choline are carbon precursors of aerobic methane formation. Once generated, methane is widely considered to be physiologically inert in eukaryotes, but several studies have found association between mammalian methanogenesis and gastrointestinal (GI) motility changes. In addition, a number of recent reports demonstrated anti-inflammatory potential for exogenous methane-based approaches in model anoxia-reoxygenation experiments. It has also been convincingly demonstrated that methane can influence the downstream effectors of transiently increased ROS levels, including mitochondria-related pro-apoptotic pathways during ischemia-reperfusion (IR) conditions. Besides, exogenous methane can modify the outcome of gasotransmitter-mediated events in plants, and it appears that similar mechanism might be active in mammals as well. This review summarizes the relevant literature on methane-producing processes in eukaryotes, and the available results that underscore its bioactivity. The current evidences suggest that methane liberation and biological effectiveness are both linked to cellular redox regulation. The data collectively imply that exogenous methane influences the regulatory mechanisms and signaling pathways involved in oxidative and nitrosative stress responses, which suggests a modulator role for methane in hypoxia-linked pathologies.

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Section: Anti-inflammatory and Anti-apoptotic Effects During Ischemiamentioning

confidence: 99%

Methane Production and Bioactivity-A Link to Oxido-Reductive Stress

Boros

Keppler

2019

Front. Physiol.

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“…Xanthine oxidase (XO; EC 1.17.3.2) has been considered as significantly potent drug target for the cure and management of pathological conditions prevailing due to high levels of uric acid in the blood stream. [10–17]. Considering the above fact, by inhibiting XO selectively could be better treatment plan for disorders caused by XO directly or indirectly including gout, inflammatory disease, oxidative damage and cancer [3, 18, 19].…”

Section: Introductionmentioning

confidence: 99%

In silico design and synthesis of targeted rutin derivatives as xanthine oxidase inhibitors

2019

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Background Xanthine oxidase is an important enzyme of purine catabolism pathway and has been associated directly in pathogenesis of gout and indirectly in many pathological conditions like cancer, diabetes and metabolic syndrome. In this research rutin, a bioactive flavonoid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase. Objective To develop new xanthine oxidase inhibitors from natural constituents along with antioxidant potential. Method In this report, we designed and synthesized rutin derivatives hybridized with hydrazines to form hydrazides and natural acids to form ester linkage with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. Results The enzyme kinetic studies performed on rutin derivatives showed a potential inhibitory effect on XO ability in competitive manner with IC 50 value ranging from 04.708 to 19.377 µM and RU3a 3 was revealed as most active derivative. Molecular simulation revealed that new rutin derivatives interacted with the amino acid residues PHE798, GLN1194, ARG912, GLN 767, ALA1078 and MET1038 positioned inside the binding site of XO. Results of antioxidant activity revealed that all the derivatives showed very good antioxidant potential. Conclusion Taking advantage of molecular docking, this hybridization of two natural constituent could lead to desirable xanthine oxidase inhibitors with improved activity. Electronic supplementary material The online version of this article (10.1186/s13065-019-0585-8) contains supplementary material, which is available to authorized users.

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“…The later attenuates the excessive production of ROS and preserves mitochondrial function. Moreover, recent publication of the same group shows that CH 4 is able to influence the levels of NO, particular via regulatory effect on the nitrite reductase activity ( 1 ).…”

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confidence: 99%