Prevention of the ultraviolet effects on clinical and histopathological changes, as well as the heat shock protein-70 expression in mouse skin by topical application of algal UV-absorbing compounds

doi:10.1016/j.jdermsci.2009.06.004

Journal of Dermatological Science

Volume 55, Issue 3, September 2009, Pages 161-169

https://doi.org/10.1016/j.jdermsci.2009.06.004 Get rights and content

Abstract

Background

Sunscreens have long been used to protect against the acute effects of UV radiation. They can also have protective effects on chronic UV-induced changes, such as photoaging and skin cancer. Recent studies have focused on marine organisms as a source of natural bioactive molecules and some UV-absorbing algal compounds are under investigation as candidates for new natural sunscreens.

Objective

The cutaneous photoprotective ability of the mycosporine-like aminoacids (MAAs) Porphyra-334 and shinorine (P-334 + SH), high UV-absorbing compounds isolated from the red alga Porphyra rosengurttii, was evaluated by in vivo procedures in mouse skin. The expression of the heat shock protein HSP70 as a potential biomarker for acute UV damage was also investigated.

Methods

A galenic formulation containing the MAA combination of P-334 + SH was applied topically to the dorsal skin of SkhR-1 H hairless mice, which were irradiated with a single UV radiation dose of 3.87 J cm⁻² and compared with a combination of UVB- and UVA-absorbing reference filters. Clinical signs of sunburn, such as erythema and edema, as well as other quantifiable histological and biochemical parameters, such as the expression of the heat shock protein 70 and antioxidant enzyme activities, were measured from skin biopsies at 6, 24, 48 and 72 h post-radiation.

Results

The formulation containing MAA prevented sunburn cell formation, as well as corneum stratum, malphigian, dermal and hypodermal thickening and other structural and morphological alterations observed in biopsies of non-photoprotected skin. A significant increase in Hsp70 was observed in the epidermis of non-photoprotected mouse skin, besides a de novo expression in deeper layers. P-334 + SH protected against the significant decrease in superoxide dismutase and catalase activities observed in non-photoprotected mice.

Conclusion

The topical application of P-334 + SH protected against UV-induced skin damage in mice and contributed to maintaining the antioxidant defence system of the skin as well as Hsp70 expression.

Introduction

The UV component of sunlight is now recognized as the major environmental deleterious factor to human health. Whereas there is evidence that UVB radiation interacts directly with cellular targets like DNA, thus producing photoproducts, UVA interacts indirectly, inducing the production of reactive oxygen species (ROS). ROS, including mainly singlet oxygen (¹O₂), superoxide radical (O₂ radical dot ⁻), hydrogen peroxide (H₂O₂) and hydroxyl radical (OH), promote DNA, RNA, lipid and protein oxidation. All these processes are involved in most of the biological effects provoked by UV exposure, such as sunburn and photoallergy (acute exposure) and photoimmunosuppression, photoaging and photocarcinogenesis (chronic exposure) [1], [2], [3]. Epidemiological studies have shown an increased incidence of skin cancer over the last few years due to an increase in life expectancy and changes in recreational sun exposure patterns (including artificial UV radiation) and clothing styles. An additional potential factor is thinning of the ozone layer, which results in increased UVB exposure [4], [5].

Photoprotection is now one of the main goals in social education, in order to reduce the risk of sun exposure [6]. Sunscreens have long been used to protect against the acute effects of UV radiation and they can also have protective effects on chronic UV-induced changes, such as photoaging and skin cancer [7], [8]. The relative effectiveness of sunscreens is mainly evaluated on the basis of their ability to prevent erythema in human skin, the so-called sun protection factor (SPF). However, the action spectrum for sunburn is heavily weighted in the UVB range (280–315 nm), with a very small contribution from UVA (315–400 nm) [9]. The increasingly recognized role of UVA in aging and, possibly, in the development of melanoma determines a crucial need to obtain valuable combinations of highly efficient and photostable filters affording optimally balanced protection against both UVA and UVB [3].

Recent studies have focused on marine organisms as a source of natural bioactive molecules with therapeutic properties, which are being exploited in a multitude of commercial applications. Algae, besides constituting an important food source in Asian countries, are able to produce substances with anti-microbial, anti-carcinogenic, anti-inflammatory and antioxidant properties with possible applications in the cosmetic, nutrition and pharmaceutical industry sectors [10], [11], [12]. Mycosporine-like aminoacids (MAAs) are secondary metabolites, with high absorption in the UV region of the solar spectrum, that have been identified in a wide variety of marine algae. The physico-chemical properties of these substances suggest their potential application as natural sunscreens in the cosmetic industry [13], [14], [15], [16]. However, the in vivo photoprotective effectiveness of these molecules incorporated into topical formulations remains unknown.

The aim of this study was to evaluate the photoprotective capability of Porphyra-334 and shinorine, MMAs isolated from the red alga Porphyra rosengurttii, on mouse skin irradiated with solar-simulated UV radiation. The specific spectral characteristics of MAAs, which have high UVA absorption properties, enabled analysis of several markers of actinic damage, apart from specific UVB biormarkers (i.e. erythema). Histological determination of the thickening of the various skin layers, together with sunburn cell formation, was evaluated. The activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase, highly affected by UVB and UVA, were also evaluated. And finally, the long-term expression of the heat shock protein 70 was evaluated after UV radiation exposure. The Hsp 70 family consists of both constitutively expressed chaperone proteins and inducible members (mainly HSP72). Hsp70 is described as a stress protein induced by many different agents, including arsenic exposure, heavy metals, infrared laser radiation and heat shock [17], [18], [19], [20]. However, research related to the effects of UV radiation on the expression of these proteins is scarce [21], [22], [23]. This is the first analysis of the delayed accumulation of Hsp70 in mouse skin after exposure to UVB + UVA radiation.

Section snippets

Experimental animals

Female albino hairless mice (Skh: hr-1), aged 8–10 weeks, were obtained from the Charles River Laboratories (Wilmington, MA). The animals were group-housed under pathogen-free conditions, in controlled temperature (23 ± 2 °C), humidity (60–70%) and visible light (12 h light/12 h dark). They were allowed ad libitum access to water and commercial mouse diet. The experiments were performed with the approval of the University Ethics Committee according to the European Community guiding principles for

Clinical and histophathological analysis

Exposure to an UV dose of 3.87 J cm⁻² induced significant erythema (medium score for erythema = 3.75) (p > 0.05) in the untreated and exposed animals (N_TI) as well as in those treated with vehicle (V) (medium score for erythema = 4) just 6 h after irradiation, as observed in Fig. 3A. Animals treated topically with P-334 + SH and reference formulations showed a lower redness level (media scores for erythema: 2 and 1.75, respectively). The initial erythemic response in P-334 + SH and reference treatments

Discussion

This study reports the photoprotective ability of the MMA combination P-334 + SH in the skin of SKhR-1H hairless mice exposed to solar-simulated UV radiation.

Mycosporine-like aminoacids are secondary metabolites identified in a wide variety of marine algae and characterized by a cyclohexenone or cyclohexenimine chromophore conjugated with the nitrogen substituent of an aminoacid or its imino alcohol. They have a molecular weight of around 300 and very high absorption properties in the UV region,

Acknowledgements

The authors thank Rosa Castillo (Dermatological Service of Hospital Virgen de la Victoria, Malaga, Spain) for her crucial participation in the experiments and Maria Jose Lozano (Anatomical Pathology Department. Faculty of Medicine, University of Malaga) for her laboratory assistance. Financial support was provided by the Spanish Ministry of Education and Science (AGL 2005-02655) and the Junta de Andalucía (RNM-295).

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Prevention of the ultraviolet effects on clinical and histopathological changes, as well as the heat shock protein-70 expression in mouse skin by topical application of algal UV-absorbing compounds

Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Experimental animals

Clinical and histophathological analysis

Discussion

Acknowledgements

J Photochem Photobiol

Clin Dermatol

J Am Acad Dermatol

J Photochem Photobiol

J Photochem Photobiol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

Biochem Pharmacol

J Biol Chem

Anal Biochem

J Dermatol Sci

J Invest Dermatol

J Invest Dermatol

Biochem Biophys Res Commun

Blood

J Dermatol Sci

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

Mechanism of immune suppression by ultraviolet radiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology

J Exp Med

Photoaging of human skin

Photodermatol Photoimmunol Photomed

Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis

Int J Dermatol

Risk reduction for non-melanoma skin cancer with childhood sunscreen use

Arch Dermatol