Reactive Oxygen Species Generation in Human Cells by a Novel Magnetic Resonance Imaging Contrast Agent

Wang, Li; Lin, Eric W.; Johansen, Mary; Madden, Timothy; Felix, Edward; Martirosyan, Karen S.; Frank, Steven J.

doi:10.1155/2018/6362426

Cited by 3 publications

(3 citation statements)

References 25 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To further confirm whether IRTO can reflect the change of the mitochondrial ROS level in live cells, the effect of lipopolysaccharide (LPS, an ROS accelerator), N -acetyl- l -cysteine (NAC, an ROS inhibitor), and mitoquinone mesylate (MitoQ, a mitochondrial ROS scavenger) , on TO release in HeLa cells was investigated by a flow cytometry assay. As shown in Figure A, compared with the untreated cells, LPS (ROS accelerator) treatment caused an enhancement of TO fluorescence in cells, and the degree of the enhancement increased with the LPS treatment time.…”

Section: Results and Discussionmentioning

confidence: 99%

Heptamethine Cyanine-Based Molecule Release Triggered by Mitochondrial ROS

Liu,

Yan,

Liu

et al. 2023

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

Conditionally activated molecule release in live cells would provide spatiotemporal control for the study and intervention of biological processes, e.g., bioactive molecule monitoring and controlled drug release. Mitochondria are the main sites of reactive oxygen species (ROS) production in cells. Here, we report an ROS-triggered molecule release strategy in mitochondria. A molecule IRTO with dual targeting groups was designed by covalently linking IR-780 (a mitochondrial targeted heptamethine cyanine) and 4-aminobutyl-thiazole orange (NH 2 -TO, a nuclear dye). IRTO diffused into live cells and first accumulated in mitochondria. As the cyanine moiety reacted with mitochondrial ROS directly or with the help of mitochondrial cytochromes, NH 2 -TO was released, escaped from mitochondria, and finally located in the nucleus. This process could be visualized by fluorescent imaging, i.e., red fluorescence (from the cyanine moiety of IRTO) first located in mitochondria, and green fluorescence (from NH 2 -TO) appeared and gradually enhanced in the nucleus with the increase of incubation time. The addition of H 2 O 2 or lipopolysaccharide (LPS, an ROS accelerator) could accelerate the release of NH 2 -TO, whereas N-acetyl-L-cysteine (NAC, an ROS inhibitor) and mitoquinone mesylate (MitoQ, a mitochondrial ROS scavenger) could obviously decrease the release of NH 2 -TO. These results suggest that IRTO could serve as a fluorescent probe for monitoring ROS in mitochondria and that IR-780 might be a promising endogenous ROS-triggered molecule release platform.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Heptamethine Cyanine-Based Molecule Release Triggered by Mitochondrial ROS

Liu,

Yan,

Liu

et al. 2023

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

show abstract

“…Also, excessive generation of ROS may stimulate inflammatory processes [18]. Previous work has shown that complexing NAC with Co(II) seems to prevent cobalt-related toxicity in the prostate and periprostatic tissues after injection [7] and that C4 does not prompt excess ROS generation in human cancer cells or normal tongue cells [19]; nevertheless, little was known of the potential for acute or chronic systemic toxicity from C4 in vivo . Here, we showed that a single intramuscular injection of C4 at a concentration 10 times than intended for clinical use, or 100 times more than what would be released from the spontaneous rupture of 120 MRI markers in a human prostate, led to no acute or chronic systemic toxicity or inflammation, no microscopic damage to brain, spinal cord, lung, heart, liver, kidney, or spleen, and no changes in the body or organ weights or in the clinical blood analyses.…”

Section: Discussionmentioning

confidence: 99%

Toxicity Evaluation of a Novel Magnetic Resonance Imaging Marker, CoCl2-N-Acetylcysteine, in Rats

Wang

Gagea

Martirosyan

et al. 2018

Journal of Toxicology

Self Cite

View full text Add to dashboard Cite

C4 (cobalt dichloride-N-acetylcysteine [1% CoCl2:2% NAC]) is a novel magnetic resonance imaging contrast marker that facilitates visualization of implanted radioactive seeds in cancer brachytherapy. We evaluated the toxicity of C4. Rats were assigned to control (0% CoCl2:NAC), low-dose (0.1% CoCl2:2% NAC), reference-dose (C4), and high-dose (10% CoCl2:2% NAC) groups. Agent was injected into the left quadriceps femoris muscle of the rats. Endpoints were organ and body weights, hematology, and serum chemistry and histopathologic changes of tissues at 48 hours and 28 and 63 days after dosing. Student's t tests were used. No abnormalities in clinical signs, terminal body and organ weights, or hematologic and serum chemistry were noted, and no gross or histopathologic lesions of systemic tissue toxicity were found in any treatment group at any time point studied. At the site of injection, concentration-dependent acute responses were observed in all treatment groups at 48 hours after dosing and were recovered by 28 days. No myofiber degeneration or necrosis was observed at 28 or 63 days in any group. In conclusion, a single intramuscular dose of C4 produced no acute or chronic systemic toxicity or inflammation in rats, suggesting that C4 may be toxicologically safe for clinical use in cancer brachytherapy.

show abstract

“…Common metals such as copper, cobalt, mercury and zinc also induce ROS production, although an association between ROS production by these compounds and inflammasome activation remains yet to be described [45][46][47][48]. ROS and low-molecular-weight hyaluronic acid (LMWHA) involvement in both priming and activation of the NLRP3 inflammasome.…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

NLRP3 Inflammasome and Allergic Contact Dermatitis: A Connection to Demystify

et al. 2020

View full text Add to dashboard Cite

Allergic contact dermatitis is a common occupational disease that manifests as a cell-mediated hypersensitivity reaction following skin exposure to small reactive chemicals termed haptens. Haptens penetrate the stratum corneum and covalently modify proteins in the epidermis, inducing intracellular stress, which further leads to the release of damage-associated molecular patterns (DAMPs), such as uric acid, reactive oxygen species, hyaluronic acid fragments and extracellular adenosine triphosphate (ATP). These DAMPs are recognized by pattern recognition receptors (PRRs) in innate immune cells, namely dendritic cells (DCs), leading to their maturation and migration to the draining lymph nodes where they activate naïve T lymphocytes. Among all PRRs, several studies emphasize the role of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome on the allergic contact dermatitis (ACD) sensitization phase. However, skin allergens—danger signals—NLRP3 inflammasome axis is yet to be completely elucidated. Therefore, in this review, we sought to discuss the molecular mechanisms underlying DAMPs release and NLRP3 inflammasome activation triggered by skin allergens. The elucidation of these key events might help to identify novel therapeutic strategies for ACD, as well as the development of nonanimal alternative methods for the identification and potency categorization of skin sensitizers.

show abstract

Reactive Oxygen Species Generation in Human Cells by a Novel Magnetic Resonance Imaging Contrast Agent

Cited by 3 publications

References 25 publications

Heptamethine Cyanine-Based Molecule Release Triggered by Mitochondrial ROS

Heptamethine Cyanine-Based Molecule Release Triggered by Mitochondrial ROS

Toxicity Evaluation of a Novel Magnetic Resonance Imaging Marker, CoCl2-N-Acetylcysteine, in Rats

NLRP3 Inflammasome and Allergic Contact Dermatitis: A Connection to Demystify

Contact Info

Product

Resources

About