Efficient Nitric Oxide Scavenging by Urea‐Functionalized Push‐Pull Chromophore Modulates NO‐Mediated Diseases

Roy, Himadri Shekar; Neethu, K M; Rajput, Swati; Sadhukhan, Sreyanko; Gowri, Vijayendran; Dar, Arif Hassan; Monga, M.; Salaria, Navita; Guha, Rajdeep; Chattopadhyay, Naibedya; Jayamurugan, Govindasamy; Ghosh, Deepa

doi:10.1002/chem.202301748

Cited by 3 publications

(2 citation statements)

References 82 publications

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“…The effects of urea on NO production have been widely observed both in vitro and in vivo; urea and NO metabolic cycles, indeed, are strongly intertwined, as they share substrates, enzymes, and transporters, including argininosuccinic acid synthase and argininosuccinic acid lyase [55,56]. Indeed, clinical studies in subjects affected by congenital urea cycle enzyme defects, which pathologically accumulate urea in the body, showed reducing circulating NO levels [57]. However, very scant literature exists concerning the effect of high urea concentration on nitric oxide synthase expression.…”

Section: Discussionmentioning

confidence: 99%

Exposure of Zebrafish Embryos to Urea Affects NOS1 Gene Expression in Neuronal Cells

Cacialli,

Ricci,

Frabetti

et al. 2024

Environments

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Nitrogen-based fertilizers represent the most common fertilization tools, particularly used in crop food agriculture, despite the low cost-efficiency and the high negative environmental impact. At present, there is still inadequate information available about the effects of urea on human health; nevertheless, previous studies in animals observed that high urea concentration exposure can damage different tissues, including the brain. In several vertebrates, a crucial factor involved in neuronal cell formation is represented by the gas molecule, nitric oxide (NO), derived from the conversion of arginine to citrulline through the enzymatic activity of nitric oxide synthases (NOS). In zebrafish, three different isoforms of the NOS gene are known: nos1, nos2a, and nos2b. In the present study we show that nos1 represents the unique isoform with a stable high expression in the brain and spinal cord during all the embryonic stages of zebrafish development. Then, by using a specific transgenic zebrafish line, Tg(HuC:GFP), to mark neuronal cells, we observed nos1 to be specifically expressed in neurons. Interestingly, we observed that urea exposure at sub-lethal doses affected cell proliferation and the number of nos1-expressing cells, inducing apoptosis. Consistently, brain NO levels were observed to be reduced in urea-treated animals compared to untreated ones. This finding represents the first evidence that urea exposure affects the expression of a key gene involved in neuronal cell formation during embryonic development.

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Section: Discussionmentioning

confidence: 99%

Exposure of Zebrafish Embryos to Urea Affects NOS1 Gene Expression in Neuronal Cells

Cacialli,

Ricci,

Frabetti

et al. 2024

Environments

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“…Push–pull conjugated small molecules are one of the most promising classes of organic semiconducting materials. Varying different structural parameters, such as the type of electron donor and electron acceptor units or their quantity and sequence within the molecule, allows fine-tuning both the spectral and other set of properties. − Push–pull chromophores have been widely used in biological and medical applications for the modulation of NO-mediated diseases, PDT, − and bioimaging. , One of the most promising electron donor blocks is triphenylamine, ,,, which has been used to obtain biocompatible organic materials. − Recently, we reported on push–pull molecules based on triphenylamine with both photovoltage and photocurrent photoresponses in biological electrolyte solution comparable to those of the human eye cones and rods. , …”

Section: Introductionmentioning

confidence: 99%

Nanoparticles of Push–Pull Triphenylamine-Based Molecules for Light-Controlled Stimulation of Neuronal Activity

Luponosov,

Solodukhin,

Aseyev

et al. 2024

ACS Biomater. Sci. Eng.

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Organic semiconductor materials with a unique set of properties are very attractive for interfacing biological objects and can be used for noninvasive therapy or detection of biological signals. Here, we describe the synthesis and investigation of a novel series of organic push−pull conjugated molecules with the starshaped architecture, consisting of triphenylamine as a branching electron donor core linked through the thiophene π-spacer to electron-withdrawing alkyl-dicyanovinyl groups. The molecules could form stable aqueous dispersions of nanoparticles (NPs) without the addition of any surfactants or amphiphilic polymer matrixes with the average size distribution varying from 40 to 120 nm and absorption spectra very similar to those of human eye retina pigments such as rods and green cones. Variation of the terminal alkyl chain length of the molecules forming NPs from 1 to 12 carbon atoms was found to be an efficient tool to modulate their lipophilic and biological properties. Possibilities of using the NPs as light nanoactuators in biological systems or as artificial pigments for therapy of degenerative retinal diseases were studied both on the model planar bilayer lipid membranes and on the rat cortical neurons. In the planar bilayer system, the photodynamic activity of these NPs led to photoinactivation of ion channels formed by pentadecapeptide gramicidin A. Treatment of rat cortical neurons with the NPs caused depolarization of cell membranes upon light irradiation, which could also be due to the photodynamic activity of the NPs. The results of the work gave more insight into the mechanisms of light-controlled stimulation of neuronal activity and for the first time showed that fine-tuning of the lipophilic affinity of NPs based on organic conjugated molecules is of high importance for creating a bioelectronic interface for biomedical applications.

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On-demand release of a selective MMP-13 blocker from an enzyme-responsive injectable hydrogel protects cartilage from degenerative progression in osteoarthritis

Roy,

Murugesan,

Kulkarni

et al. 2024

J. Mater. Chem. B

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Efficient Nitric Oxide Scavenging by Urea‐Functionalized Push‐Pull Chromophore Modulates NO‐Mediated Diseases

Cited by 3 publications

References 82 publications

Exposure of Zebrafish Embryos to Urea Affects NOS1 Gene Expression in Neuronal Cells

Exposure of Zebrafish Embryos to Urea Affects NOS1 Gene Expression in Neuronal Cells

Nanoparticles of Push–Pull Triphenylamine-Based Molecules for Light-Controlled Stimulation of Neuronal Activity

On-demand release of a selective MMP-13 blocker from an enzyme-responsive injectable hydrogel protects cartilage from degenerative progression in osteoarthritis

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