Skin organ culture as a model to study oxidative stress, inflammation and structural alterations associated with UVB‐induced photodamage

Portugal-Cohen, Meital; Soroka, Yoram; Frušić-Zlotkin, Marina; Verkhovsky, Lilian; Brégégère, François; Neuman, Rami; Kohen, Ron; Milner, Yoram

doi:10.1111/j.1600-0625.2011.01317.x

Cited by 45 publications

(39 citation statements)

References 82 publications

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“…An organ culture model may reflect the biological effects of UV light and reproduces coordinated features of skin responses. Hence, it is expected to mimic living skin when subjected to various challenges, something that cell cultures cannot always perform [88]. It was interesting to observe that the activation of HO-1 in the whole skin was similar to the activation observed in the cells in culture.…”

Section: Discussionmentioning

confidence: 66%

Can nitroxides evoke the Keap1–Nrf2–ARE pathway in skin?

Greenwald

Anzi²,

Sasson³

et al. 2014

Free Radical Biology and Medicine

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Section: Discussionmentioning

confidence: 66%

Can nitroxides evoke the Keap1–Nrf2–ARE pathway in skin?

Greenwald

Anzi²,

Sasson³

et al. 2014

Free Radical Biology and Medicine

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“…We and others have reported that nitrite can serve as a source of NO through XOR in models of vascular injury and pulmonary hypertension (23,24). XOR has been detected in skin, where it is involved in ROS production in response to lipopolysaccharide (LPS) (25) and ultraviolet irradiation (26). Thus, we hypothesize that XOR participates in normal wound healing through ROS/RNS and NO production.…”

Section: Xanthine Oxidoreductase Function Contributes To Normal Woundmentioning

confidence: 82%

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing

Madigan

McEnaney

Shukla

et al. 2015

Mol Med

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Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H 2 O 2 , 0.15%) or allopurinol (30 μg) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H 2 O 2 and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H 2 O 2 restored wound healing in tungsten-fed mice. In vitro, nitrite and H 2 O 2 both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production.

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“…Following treatments, the epidermis was separated, as described before [18]. Briefly, the skin explants were incubated for 1 min in PBS at 56°C, after which the epidermis was physically detached from the dermis using forceps and scalpel.…”

Section: Methodsmentioning

confidence: 99%

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

Kahremany

Babaev

Gvirtz

et al. 2019

Skin Pharmacol Physiol

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Background/Aims: The Nrf2 signaling pathway plays a pivotal role in neutralizing excess reactive oxygen species formation and therefore enhancing the endogenous cellular protection mechanism. Thus, activating this pathway may provide therapeutic options against oxidative stress-related disorders. We have recently applied a computer-aided drug design approach to the design and synthesis of novel Nrf2 enhancers. The current study was aimed at investigating the potential beneficial impact of (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) in skin oxidative damage models. Methods: SK-119, tested initially in PC-12 cells, attenuated oxidative stress-induced cytotoxicity concomitantly with Nrf2 activation. The potential impact of this compound was evaluated in skin-based disease models both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Results: The data clearly showed the marked anti-inflammatory and photoprotection properties of the compound; SK-119-treated cells or tissues displayed a reduction in cytokine secretion induced by lipopolysaccharides (LPS) in a manner comparable with dexamethasone. In addition, topical application of SK-119 was able to block UVB-induced oxidative stress and attenuated caspase-mediated apoptosis, DNA adduct formation, and the concomitant cellular damage. Conclusion: These results indicate that SK-119 is an Nrf2 activator that can be used as a prototype molecule for the development of novel treatments of dermatological disorders related to oxidative stress.

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Skin organ culture as a model to study oxidative stress, inflammation and structural alterations associated with UVB‐induced photodamage

Abstract: Skin organ culture proved to be an integrated model appropriate for in vitro analysis of UVB biologic effects and their correlations, and for the study of non-invasive diagnostic methods in cellular and molecular terms.

Cited by 45 publications

References 82 publications

Can nitroxides evoke the Keap1–Nrf2–ARE pathway in skin?

Can nitroxides evoke the Keap1–Nrf2–ARE pathway in skin?

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

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