Animal models of skin disease for drug discovery

Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; Melo, Wanessa Cma de; Huang, Ying‐Ying; Yin, Rui; Chandran, Rakkiyappan; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore T.; Hamblin, Michael R.

doi:10.1517/17460441.2013.761202

Cited by 98 publications

(79 citation statements)

References 175 publications

(237 reference statements)

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“…In addition to the recruitment of FADD, the Fas-induced apoptosis pathway can also be mediated by a receptor-interacting protein (RIP), RIP associated ICH/CED-3-homologous protein with a death domain, and procaspase-2 [13]. Fas-mediated apoptosis of keratinocytes has multiple functions and has been implicated in various conditions such as allergic contact dermatitis, wound healing, lupus erythematosus, toxic epidermal necrolysis, and the formation of sunburn cells by UV radiation [14]. Recent studies have demonstrated Fas expression associated with apoptotic keratinocytes in aging human epidermis [15].…”

Section: Resultsmentioning

confidence: 99%

Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent System

Park

Oh²,

Kim³

et al. 2017

Pharmacology

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Previously, we have shown that extracellular basic pH plays a significant role in both the direct and indirect regulation of cellular processes in a wound; this in turn affects the wound-healing process. Several studies have demonstrated the importance of apoptosis modulation in the wound-healing process, especially in removing inflammatory cells and in inhibiting scar formation. However, the effects of extracellular basic pH on wound healing-related skin damage are yet to be examined. Therefore, we investigated the induction of accelerated apoptosis by extracellular basic pH in skin. Apoptosis-related protein levels were measured using an array kit, target protein expression levels were detected by immunostaining, lactate dehydrogenase was analyzed spectrophotometrically, and Annexin V levels were measured by fluorescence staining. Basic pH (8.40) strongly upregulated extrinsic apoptosis proteins (Fas, high temperature requirement A, and p21) and slightly upregulated intrinsic apoptosis proteins (cytochrome c, B-cell lymphoma 2 [Bcl-2], Bcl-2-associated death promoter, and Bcl-2-like protein 4) in a 3D human skin equivalent system. Moreover, basic pH (8.40) induced heat shock protein (HSP) 60 and 70. In addition, basic pH-exposed Fas- and HSP60-knockdown cells showed significantly decreased levels of apoptosis. Taken together, these results indicate that extracellular basic pH increases early-stage apoptosis through Fas/FasL via modulation of HSP60 and HSP70.

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Section: Resultsmentioning

confidence: 99%

Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent System

Park

Oh²,

Kim³

et al. 2017

Pharmacology

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“…; Avci et al . ). In addition, the vast majority of preclinical studies have been performed using assay conditions ( e.g .…”

Section: Nutraceuticals Purported To Counter the Skin Ageing Processmentioning

confidence: 97%

Nutraceuticals and skin appearance: Is there any evidence to support this growing trend?

Spiro

Lockyer

2018

Nutrition Bulletin

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The rise of the nutraceutical market, specifically oral nutrition supplements claiming to improve skin appearance, is striking. This paper aims to examine the published scientific evidence for beneficial effects of nutraceuticals on skin appearance. An overview of skin physiology and intrinsic and extrinsic ageing is provided which underlies the potential physiological processes nutraceuticals purport to counter. Common ingredients used are explored. Some of these (vitamins A, C, B2, B3, B7, copper, iodine, zinc) have authorised skin‐related health claims, but many do not. Current evidence for those without existing authorised claims (e.g. green tea extract, pomegranate extract, carotenoids, evening primrose oil, borage oil, fish oil, collagen and co‐enzyme Q10) is reviewed, focussing primarily on evidence from randomised controlled trials where available, in relation to skin parameters including wrinkles and hydration. Issues of safety are also considered, and the postulated mechanisms for some emerging ingredients, such as cocoa flavanols and probiotics, are explored. Evidence from high quality human trials demonstrating clear benefit is required by regulatory authorities in order for foods and nutrition supplements to carry a health or beauty claim. To date, the evidence for many ingredients in relation to skin appearance is limited, not sufficiently robust and/or inconsistent. Although there are a small number of human studies suggesting a potential benefit and some plausible biological mechanisms, much of the evidence to date comes from animal and in vitro studies. There are simply not enough good quality randomised controlled trials in this area to draw firm conclusions about the benefit of nutraceuticals to skin appearance.

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“…Mitochondria play crucial roles in several age-related diseases, and in the physiology of normal skin aging [37]. The effects of skin photodamage and aging are studied by the use of animal models [38].…”

Section: Role Of Mitochondriamentioning

confidence: 99%

“…Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia [38].…”

Section: Age-related Diseases Disorders and Conditions Of The Skinmentioning

confidence: 99%

Review of Major Theories of Skin Aging

Gragnani

Cornick²,

Chominski³

et al. 2014

AAR

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Here we aim to describe each factor that leads to skin aging and describe their mechanisms. A PubMed database searches (from January 2004 to March 2014) using aging and skin as searched terms. There are substantial evidences showing that aging is associated with damage from free radicals represented by various reactive oxygen species (ROS). Mitochondria are producers and also targets of oxidative stress. The cycle of mitochondrial dysfunction can trigger the aging process. In the cellular senescence and telomeres theory, the diploid cells exhibit a limited proliferation potential. After a finite number of divisions, they enter a state of senescence with a stop replication in cell proliferation. It is suggested that aging is associated mainly with hyper-regulation of apoptosis. Obesity presumably accelerates the process of aging, which is aggravated by smoking. And the influence of the environment, called solar UV irradiation is of considerable importance to skin aging. There are several mechanisms that trigger the natural aging process and contribute to age-related changes, including oxidative stress theory of free radicals, the mitochondrial dysfunction, telomere shortening, UV radiation and other mechanisms that taken together or alone may or not accelerate the change in skin.

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Animal models of skin disease for drug discovery

Cited by 98 publications

References 175 publications

Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent System

Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent System

Nutraceuticals and skin appearance: Is there any evidence to support this growing trend?

Review of Major Theories of Skin Aging

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