In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

Asghar, Muhammad Nadeem; Emani, Rohini; Alam, Catharina; Helenius, Terhi O.; Grönroos, Tove J.; Sareila, Outi; U-Din, Mueez; Holmdahl, Rikard; Hänninen, Arno; Toivola, Diana M.

doi:10.1097/mib.0000000000000118

Cited by 27 publications

(24 citation statements)

References 62 publications

(108 reference statements)

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“…This is in accordance with previous studies where L-012 is used to image ROS during various conditions of acute inflammation. 15,17 Interestingly, the signal strength generated by L-012 in models of arthritis and skin inflammation is lower than the signal we observe in a healthy ileum. However, it resembles the amount of signal in models of colonic inflammation.…”

Section: Discussioncontrasting

confidence: 74%

“…To address temporal and spatial in vivo ROS production, we exploited the luminescent probe L-012 as an imaging marker for ROS. [15][16][17][18] We observed a strong L-012-mediated signal in ileum that we believe is the result of epithelial cell secretion of superoxide and NO, with a resultant peroxynitrite formation. This is supported by the following: firstly, L-012 is recognized to act extracellularly, and with a high specificity and sensitivity to peroxynitrite.…”

Section: Discussionmentioning

confidence: 69%

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iNOS- and NOX1-dependent ROS production maintains bacterial homeostasis in the ileum of mice

et al. 2018

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The intestinal epithelial cells constitute the first line of defense against gut microbes, which includes secretion of various antimicrobial substances. Reactive oxygen species (ROS) are well characterized as part of the innate phagocytic immunity; however, a role in controlling microorganisms in the gut lumen is less clear. Here, we show a role for nitric oxide synthase (iNOS)- and NOX1-produced ROS in maintaining homeostasis of the gut microbiota. In vivo imaging revealed distinctly high levels of ROS in the ileum of normal healthy mice, regulated in accordance with the amount of gut bacteria. The ROS level was dependent on the nitric oxide and superoxide producers iNOS and NOX1, respectively, suggesting peroxynitrite as the effector molecule. In the ileum of iNOS- and NOX1-deficient mice, the bacterial load is increased and the composition is more cecum like. Our data suggest a unique role of ileum in maintaining homeostasis of gut microbes through production of ROS with potential importance for preventing reflux from the large intestine, bacterial overgrowth, and translocation.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 69%

iNOS- and NOX1-dependent ROS production maintains bacterial homeostasis in the ileum of mice

et al. 2018

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“…Similarly, Asghar et al . () demonstrated increased ROS [superoxide (

O_{2}^{-}

) radical, hydroxyl (OH • ) radical, hydrogen peroxide (H 2 O 2 )] and RNS (NO and peroxynitrite) production in AA‐induced inflamed colonic mucosa. Furthermore, in a study by Iseri et al .…”

Section: Discussionmentioning

confidence: 99%

“…During acute inflammation, neutrophils and macrophages migrate from the blood vessels, enter the inflamed mucosa and submucosa of the large intestine, and lead to excessive production of oxygen free radicals (Suematsu et al 1987;Shiratova et al 1989;Al-Rejaie et al 2013). Similarly, Asghar et al (2014)…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential ofMyrtus communisSubsp.communisExtract Against Acetic ACID-Induced Colonic Inflammation in Rats

Şen

Yüksel

Bulut

et al. 2016

Journal of Food Biochemistry

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The aim of this study was to evaluate the effect of ethanol extract from leaves of Myrtus communis subsp. communis (MC) on acetic acid (AA)‐induced ulcerative colitis in rats. On the fourth day of colitis induction, all rats were decapitated. Colitis was assessed by macroscopic and microscopic scores and by measuring malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol, lucigenin, nitric oxid and peroxynitrite chemiluminescence (CL). Colitis caused significant increases in the colonic MDA levels, MPO activity, CL values, macroscopic and microscopic damage scores along with significant decrease in tissue GSH level. However, treatment with MC extract reversed all these biochemical indices, as well as histopathological alterations induced by AA with the protective effects being similar to that of sulphasalazine treatment. The study showed that MC extract could alleviate colitis in rats and can be considered an alternative therapeutic approach for management of inflammatory bowel diseases (IBD). Practical Applications Myrtus communis subsp. communis leaves are used as antihypertensive, antitussive, antiemetic, diuretic, antidiarrheic, cardiotonic, antidiabetic and anti‐inflammatory agents in folk medicine. This study revealed that the ethanol extract of the plant possesses significant anti‐inflammatory activity, confirming its traditional use.

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“…With respect to drug delivery to inflammatory bowel diseases such as ulcerative colitis, novel material‐based rectal formulations have shown successful facilitation of mucosal healing by using drugs in hydrogels to target the inflamed colonic mucosa or thermo‐sensitive polymer platforms in murine models of colitis. Development and use of in vivo diagnostic imaging modalities is essential to follow effects of drugs and disease progression over time, for example, for intestinal inflammation by optical imaging and PET or optical imaging of cancer growth . A crucial challenge in utilizing nanodiagnostics if the nanoparticles carry the diagnostic probe is particle integrity (e.g., that the label remain attached to the particle during imaging).…”

Section: Model Systems To Decipher Mechanisms Of Disease For Drug Scmentioning

confidence: 99%

Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems

Sahlgren

Meinander

Zhang

et al. 2017

Adv Healthcare Materials

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Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic resistance. Development within several areas of research ranging from computational sciences, material sciences, bioengineering to biomedical sciences and bioimaging is needed to realize innovative drug development and diagnostic (DDD) approaches. Here, an overview of recent progresses within key areas that can provide customizable solutions to improve processes and the approaches taken within DDD is provided. Due to the broadness of the area, unfortunately all relevant aspects such as pharmacokinetics of bioactive molecules and delivery systems cannot be covered. Tailored approaches within (i) bioinformatics and computer‐aided drug design, (ii) nanotechnology, (iii) novel materials and technologies for drug delivery and diagnostic systems, and (iv) disease models to predict safety and efficacy of medicines under development are focused on. Current developments and challenges ahead are discussed. The broad scope reflects the multidisciplinary nature of the field of DDD and aims to highlight the convergence of biological, pharmaceutical, and medical disciplines needed to meet the societal challenges of the 21st century.

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In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

Abstract: In vivo imaging using L-012 is a useful, simple, and cost-effective tool to study the level and longitudinal progression of genetic and possibly chemical murine colitis.

Cited by 27 publications

References 62 publications

iNOS- and NOX1-dependent ROS production maintains bacterial homeostasis in the ileum of mice

iNOS- and NOX1-dependent ROS production maintains bacterial homeostasis in the ileum of mice

Therapeutic Potential ofMyrtus communisSubsp.communisExtract Against Acetic ACID-Induced Colonic Inflammation in Rats

Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems

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