Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser

Hotta, Yuji; Ieda, Naoya; Fukamoto, Ayako; Kataoka, Tomoya; Kawade, Yoshihiro; Maeda, Yasuhiro; Nakagawa, Hidehiko; Kimura, Kazunori

doi:10.4111/icu.2016.57.3.215

Cited by 10 publications

(4 citation statements)

References 21 publications

(25 reference statements)

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“…Indeed, NO–aspirin compounds have been shown to provide anti-inflammatory benefits without the formation of gastric ulcers that are caused by comparable exposure to aspirin alone [ 145 ]. Applications for light-activated NO releasers are still in their infancy, although promising work has been reported on vascular relaxation in rats [ 142 , 146 , 147 ].…”

Section: Roles For No Evolution During Infection and Prospects For Dr...mentioning

confidence: 99%

The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications

et al. 2022

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Nitric oxide was once considered to be of marginal interest to the biological sciences and medicine; however, there is now wide recognition, but not yet a comprehensive understanding, of its functions and effects. NO is a reactive, toxic free radical with numerous biological targets, especially metal ions. However, NO and its reaction products also play key roles as reductant and oxidant in biological redox processes, in signal transduction, immunity and infection, as well as other roles. Consequently, it can be sensed, metabolized and modified in biological systems. Here, we present a brief overview of the chemistry and biology of NO—in particular, its origins in geological time and in contemporary biology, its toxic consequences and its critical biological functions. Given that NO, with its intrinsic reactivity, appeared in the early Earth’s atmosphere before the evolution of complex lifeforms, we speculate that the potential for toxicity preceded biological function. To examine this hypothesis, we consider the nature of non-biological and biological targets of NO, the evolution of biological mechanisms for NO detoxification, and how living organisms generate this multifunctional gas.

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Section: Roles For No Evolution During Infection and Prospects For Dr...mentioning

confidence: 99%

The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications

et al. 2022

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“…As another example, we also succeeded in photomanipulating vasodilation of the rat penile corpus cavernosum (see ref. 28). Therefore, NOBL 1 is expected to be a valuable research tool, as well as a candidate therapeutic drug for various circulatory system diseases.…”

Section: A Blue Light Controllable No Releaser Noblmentioning

confidence: 99%

Development of Photoredox-reaction-driven NO-releasing Reagents and Application for Photomanipulation of Vasodilation

Ieda¹,

Nakagawa

2020

J. Synth. Org. Chem. Jpn.

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Nitric oxide (NO) is a signaling molecule that mediates vasodilation, neurotransmission, and immune response. Due to its instability in biological environments, NO releasing small molecular compounds have been developed for biological experiments and also as therapeutic reagents for vascular diseases. Although photocontrollable NO releasers are very useful chemical tools because of their precise operability in response to light irradiation, their biological applications have been limited, mainly because they require UV light irradiation or contain metal ions with the potential to cause cytotoxicity. In order to overcome these problems, our group has developed visible light responsive NO releasers based on photoreodox reaction. These compounds are composed of two moieties, an NO releasing moiety and a light harvesting antenna moiety. After photoirradiation, photoinduced electron transfer from the NO releasing moiety to the antenna takes place, followed by NO release. Based on this system, we developed a blue light controllable NO releaser and a yellowish green light controllable one, which are applicable for cellular and ex vivo experiments. This account focuses on recent developments in photoredox driven NO releasers and their applications for spatiotemporally controlled NO release in cells and ex vivo.

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“…To solve these problems, we focused on light-reactive NO releasers that could temporally and spatially regulate NO release, thereby controlling the beginning and the end of drug effects and preventing systemic side effects. We have previously reported the use of blue light-reactive NO releaser and yellowish-green light-reactive NO releasers [ 9 10 11 ]. However, it may be difficult to regulate erectile response because these lights have low tissue permeability.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a Red-Light Controllable Nitric Oxide Releaser for Neurogenic Erectile Dysfunction: A Study Using a Rat Model of Cavernous Nerve Injury

Mori

Hotta

Ieda

et al. 2023

World J Mens Health

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Purpose Neurogenic erectile dysfunction (ED) is a common side effect of radical prostatectomy (RP) because of cavernous nerve damage. In these patients, the production of nitric oxide (NO), which is important for erection, is decreased in the corpus cavernosum. Therefore, NO donors are useful for post-RP ED. However, short half-life and systemic side effects are problems of NO application in ED therapy. To avert these problems, we developed a red-light controllable NO releaser, NORD-1. This study aimed to investigate the effect of NORD-1 and red-light irradiation on neurogenic ED using a rat model of bilateral cavernous nerve injury (BCNI). Materials and Methods BCNI and sham operations were conducted on 8-week-old rats. After 4 weeks, erectile function was evaluated using changes in intracavernous pressure (ICP) during electrostimulation of the cavernous nerve. ICP was measured under three conditions; without NORD-1 and red-light irradiation, with NORD-1 and without red-light irradiation, and with NORD-1 and red-light irradiation. SiR650 which absorbs red-light but does not release NO was used for the negative control. After the experiment, localization of NORD-1 was observed using a microscope. Results Erectile function in a BCNI rat model was significantly decreased compared to sham-operated rats (p<0.05). After injecting NORD-1 into the penis, erectile function did not change without red-light irradiation. However, the combination of NORD-1 and red-light irradiation significantly improved erectile function (p<0.05) without affecting systemic arterial pressure. In contrast, when SiR650 was used, erectile function did not change in all three conditions. NORD-1 was detected only in the corpus cavernosum and not in the urethra and dorsal vein. Conclusions NORD-1 combined with red-light irradiation is effective for ED induced by cavernous nerve injury. This treatment may have low risks of hypotension and urinary incontinence, and it can replace the current treatment for post-RP ED.

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Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser

Cited by 10 publications

References 21 publications

The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications

The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications

Development of Photoredox-reaction-driven NO-releasing Reagents and Application for Photomanipulation of Vasodilation

Efficacy of a Red-Light Controllable Nitric Oxide Releaser for Neurogenic Erectile Dysfunction: A Study Using a Rat Model of Cavernous Nerve Injury

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