reactive carbonyl
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2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jan Spaas ◽  
Wouter M. A. Franssen ◽  
Charly Keytsman ◽  
Laura Blancquaert ◽  
Tim Vanmierlo ◽  
...  

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation. Methods The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes). Results Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (β-alanyl-l-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were ~ twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects. Conclusions Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS.


2021 ◽  
Vol 12 ◽  
Author(s):  
Md. Sanaullah Biswas ◽  
Jun’ichi Mano

Oxidation of membrane lipids by reactive oxygen species (ROS) or O2/lipoxygenase leads to the formation of various bioactive compounds collectively called oxylipins. Reactive carbonyl species (RCS) are a group of oxylipins that have the α,β-unsaturated carbonyl structure, including acrolein and 4-hydroxy-(E)-2-nonenal. RCS provides a missing link between ROS stimuli and cellular responses in plants via their electrophilic modification of proteins. The physiological significance of RCS in plants has been established based on the observations that the RCS-scavenging enzymes that are overexpressed in plants or the RCS-scavenging chemicals added to plants suppress the plants’ responses to ROS, i.e., photoinhibition, aluminum-induced root damage, programmed cell death (PCD), senescence, abscisic acid-induced stomata closure, and auxin-induced lateral root formation. The functions of RCS are thus a key to ROS- and redox-signaling in plants. The chemical species involved in distinct RCS signaling/damaging phenomena were recently revealed, based on comprehensive carbonyl determinations. This review presents an overview of the current status of research regarding RCS signaling functions in plants and discusses present challenges for gaining a more complete understanding of the signaling mechanisms.


Author(s):  
N André Sasaki ◽  
Pascal Sonnet

Instead of a conventional ‘one-drug-one-target approach’, this article presents a novel multi-target approach with a concept of trapping simultaneously as many detrimental factors as possible involved in the progression of Parkinson's disease. These factors include reactive carbonyl species, reactive oxygen species, Fe3+/Cu2+ and ortho-quinones ( o-quinone), in particular. Different from the known multi-target strategies for Parkinson's disease, it is a sort of ‘vacuum cleaning’ strategy. The new agent consists of reactive carbonyl species scavenging moiety and reactive oxygen species scavenging and metal chelating moiety linked by a spacer. Provided that the capacity of scavenging o-quinones is demonstrated, this type of agent can further broaden its potential therapeutic profile. In order to support this new hypothetical approach, a number of simple in vitro experiments are proposed.


2021 ◽  
Vol 22 (18) ◽  
pp. 10026
Author(s):  
Katarzyna Bednarska ◽  
Izabela Fecka

Reactive carbonyl species (RCS) such as methylglyoxal (MGO) or glyoxal (GO) are the main precursors of the formation of advanced glycation end products (AGEs). AGEs are a major factor in the development of vascular complications in diabetes. Vasoprotectives (VPs) exhibit a wide range of activities beneficial to cardiovascular health. The present study aimed to investigate selected VPs and their structural analogs for their ability to trap MGO/GO, inhibit AGE formation, and evaluate their antioxidant potential. Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) and diode-array detector (UHPLC-DAD) was used to investigate direct trapping capacity and kinetics of quenching MGO/GO, respectively. Fluorimetric and colorimetric measurements were used to evaluate antiglycation and antioxidant action. All tested substances showed antiglycative effects, but hesperetin was the most effective in RCS scavenging. We demonstrated that rutin, diosmetin, hesperidin, and hesperetin could trap both MGO and GO by forming adducts, whose structures we proposed. MGO-derived AGE formation was inhibited the most by hesperetin, and GO-derived AGEs by diosmetin. High reducing and antiradical activity was confirmed for quercetin, rutin, hesperetin, and calcium dobesilate. Therefore, in addition to other therapeutic applications, some VPs could be potential candidates as antiglycative agents to prevent AGE-related complications of diabetes.


2021 ◽  
Vol 22 (16) ◽  
pp. 9043
Author(s):  
Kanae Mure ◽  
Susumu Tomono ◽  
Minae Mure ◽  
Mano Horinaka ◽  
Michihiro Mutoh ◽  
...  

Cigarette smoking and alcohol consumption are major risk factors for lifestyle-related diseases. Although it has been reported that the combination of these habits worsens risks, the underlying mechanism remains elusive. Reactive carbonyl species (RCS) cause chemical modifications of biological molecules, leading to alterations in cellular signaling pathways, and total RCS levels have been used as a lipid peroxidation marker linked to lifestyle-related diseases. In this study, at least 41 types of RCS were identified in the lipophilic fraction of plasma samples from 40 subjects using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Higher levels of 10 alkanals, 5 trans-2-alkenals, 1 cis-4-alkenal, and 3 alkadienals were detected in the smoking/drinking group (N = 10) as compared to those with either habit (N = 10 each) or without both habits (N = 10) in the analysis of covariances adjusted for age and BMI. The levels of 3 alkanals, 1 trans-2-alkenal, 1 alkadienal, and 1 4-hydroxy-2-alkenal in the smoking/drinking group were significantly higher than those in the no-smoking/drinking and no-smoking/no-drinking groups. These results strongly indicate that the combination of cigarette smoking and alcohol drinking synergistically increases the level and variety of RCS in the circulating blood, and may further jeopardize cellular function.


2021 ◽  
Vol 343 ◽  
pp. 128478
Author(s):  
Francisco J. Hidalgo ◽  
Cristina M. Lavado-Tena ◽  
Rosario Zamora
Keyword(s):  

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 690
Author(s):  
Giancarlo Aldini ◽  
Alessandra A. Altomare

The Special issue is composed of 13 contributions: 9 research papers and 4 reviews [...]


2021 ◽  
pp. 129403
Author(s):  
Koichi Sugimoto ◽  
Yasumasa Matsuoka ◽  
Kyoko Sakai ◽  
Norika Fujiya ◽  
Hiroyuki Fujii ◽  
...  

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