Hairless mouse model

Impairment of the retinoid signal transduction pathways occurs as a result of prolonged UV exposure. Down regulation of nuclear receptors for Vitamin A occurs,269 resulting in a functional deficiency of Vitamin A. Application of Vitamin A derivatives would appear to be an obvious treatment modality. Topical application of Vitamin A does increase the HA in the epidermal layer, increasing the thickness of the HA meshwork after prolonged treatment.270 Vitamin A thus enhances repair, as can be demonstrated in photo-aged hairless mouse model.271 The decline in GAG, and in particular HA deposition that occurs with UVB irradiation, can be entirely prevented by retinoic acid treatment. 

Orengo, I.F., Gerguis, J., Phillips, R., Guevara, A., Lewis, A.T., and Black, H.S., Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer a study in the hairless mouse model, Arch. Dermatol., 138, 751, 2002. 

Mouret et al. (2013) reported that for the SKH-1 hairless mouse model, topical application of dimercapto-chelating agents such as BAL and meso-2,3-dimercaptosuccinic acid (DMSA) were more effective than subcutaneous administration in the attenuation of lewisite vapor-induced injury. Although both agents reduced neutrophil infiltration, wound size, and necrosis of the skin barrier, BAL was found to be more effective than DMSA. 

J. H. Barker, F. Hammersen, I. Bondar, T. J. Galla, M. D. Menger, W. Gross, and K. Messmer. Direct monitoring of nutritive blood flow in a failing skin flap The hairless mouse ear skin-flap model. Plast. Reconstr. Surg. 84 303-313 (1989). 

When investigating the effects of water on transdermal permeation, animal skin may yield results markedly different to human data. For example, hairless mouse skin is unsuitable for modeling human stratum corneum regarding hydration effects the murine skin, when hydrated for 24 h, became grossly more permeable than human skin membranes [8]. Thus water effects on skin permeability obtained using animal models need cautious assessment. 

Bond, J.R., and B.W. Barry. 1986. Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin Hydration damage. J Invest Dermatol 90 486. 

Luzardo-Alvarez, A., et al. 1998. Iontophoretic permselectivity of mammalian skin Characterization of hairless mouse and porcine membrane models. Pharm Res 15 (7) 984. 

The role of mast cells and histamine inducing itch remains unclear in dry skin. It has been shown that histamine concentrations increase 48 hours following acetone treatment in a dry environment.23 A subsequent study demonstrated an increased number of mast cells and histamine levels in the dermis of hairless mice in response to low environmental humidity.46 The authors did not examine a relationship between scratching behavior with the increase in mast cells and histamine. Miyamoto et al. used the mouse model treated with water followed by 1 1 acetone ether to see if they could demonstrate an increase in mast cell number or degranulation however, they found no difference.24 Furthermore, they performed the same study on mast cell deficient mice and were able to induce a similar scratching behavior, which suggests that mast cells may not play a definite role in the mechanism of itch in dry skin. 

Skin is also an important target organ for estrogens. The estrogenic effect on skin is well characterized, as well as the effect of estrogen withdrawal. A major effect of estrogen is the increased levels of HA deposition and the associated water of hydration. Topical estrogens are also able to enhance HA deposition in skin, as documented in the hairless mouse skin model.280... 

The purpose of this report is to present results on (a) the effect of ethanol on the transport of 8-estradiol across hairless mouse skin and (b) the effect upon the effective permeability coefficient as solvent compositions are independently varied in the donor and receiver chambers. Also, since there is evidence for pore formation, at least at the highest ethanol levels, a novel pore model... 

A new theoretical model will now be described aimed at attempting to provide a possible explanation for the deviations observed in Figure 3. The model assumes that significant porosity prevails in the hairless mouse stratum corneum when ethanol is present. Although it can be assumed, that at low ethanol concentrations (below 50%) ethanol fluidizes lipid bilayers, there is evidence, that ethanol at high concentration (over 50%) may induce significant pore formations in hairless mouse stratum corneum as measured by the substantial increase of tetraethylammonium bromide permeabilities (10). The permeability coefficient P of a solute across a membrane or stratum corneum under steady state conditions may be described by ... 

Before detailed conclusions are presented with regard to the physical meaning of the present model more fundamental studies are needed. While it is clear that ethanol "induces" new pores or "activates" latent pores in hairless mouse stratum corneum at high ethanol concentrations (10), the role of ethanol at lower concentrations is less clear at this moment. It is well known (12 ) that ethanol at low concentrations, may "fluidize" bilayers, thus leading to changes in both partitioning and diffusivity. Thus a complete description for permeation through stratum corneum will have to consider the effects of adjuvants on the properties of lipid bilayers in addition to the pore model described here. 

In this chapter we summarize work from our laboratory in which we have tested these predictions. The hairless mouse is our model. Initial experiments utilized excised skin while later studies used an in vivo system. We irradiated these systems with either UVA (320 100 nm), UVB (290-320 nm), or simulated sunlight in a pattern of UVA and UVB which closely matched natural sunlight. We have measured UV-induced changes in antioxidants, lipid peroxidation, and the effects of dietary supplementation with the major chain-breaking lipophilic antioxidant, a-tocopherol, on UV-induced skin damage. 

A systematic characterization of animal models including the euthymic hairless guinea pig (HOP), weanling pig (WP), the mouse ear vesicant model (MEVM), and the hairless mouse (HM) showed that SM induced subepidermal blister formation and epidermal cell death in all models tested (Smith et al, 1997a). Hairless mice are useful models of... 

Sabourin, C.L.K., Danne, M.M. et al. (2003). Modulation of sulfur mustard-induced inflammation and gene expression by Olvanil in the hairless mouse vesicant model. J. Toxicol. Cutan. Ocular Toxicol. 22(3) 125-36. 

Bond, J. R. and Barry, B. W. Hairless mouse skin is limited as a model for assessing the effects of penetration enhancers in human skin. Journal of Investigative Dermatology 90(6) 810-813, 1988. 

Simon, G.A. and Maibach, H.I., 1998, Relevance of hairless mouse as an experimental model of percutaneous penetration in man. Skin Pharmacol. Appl. Skin Physiol, 11, 80-86. 

Rigg, PC. and Barry, B.W. (1990). Shed snake skin and hairless mouse skin as model membranes for human skin during permeation studies. Journal of Investigative Dermatology, 94 235-240. 

An ideal pharmacokinetic model of the percutaneous absorption process should be capable of describing not only the time course of penetration through skin and Into blood (or receptor fluid In a diffusion cell), but also the time course of disappearance from the skin surface and accumulation (reservoir effect) of penetrant within the skin membrane. Neither Pick s Plrst Law of Diffusion nor a simple kinetic model considering skin as a rate limiting membrane only Is satisfactory, since neither can account for an accumulation of penetrant within skin. To resolve this dilemma, we have analyzed the In vitro time course of absorption of radiolabeled benzoic acid (a rapid penetrant) and paraquat (a poor penetrant) through hairless mouse skin using a linear three compartment kinetic model (Figure 5). The three compartments correspond to the skin surface (where the Initial dose Is deposited), the skin Itself (considered as a separate compartment), and the receptor fluid In the diffusion cell. The Initial amount deposited on the skin surface Is symbolized by XIO, and K12 and K23 are first order rate constants. 

Miller, L. L., and Smith, G. A., 1989, Iontophoretic transport of acetate and carboxylate ions through hairless mouse skirL A cation exchange membrane model, 7ni. J. Pharm. 49 15-22. 

A systematic characterization of animal models including the euthymic HGP, WP, the MEVM, and tiie hairless mouse showed that SM-induced subepidermal blister formation and epidermal cell death in all models tested (Smith et al., 1997a,b,c). Hairless mice are useful models of human skin the absence of hair on tire skin and increased skin thickness reduce the rapid penetration of toxicants (Walter and DeQuoy, 1980). Thus, the hairless mouse has emerged as an effective model for characterizing vesicant injury mechanisms and for early screening of candidate therapeutics (Blank et al., 2000 Casillas et al., 2000a,b Ricketts et al., 2000 Sabourin et al., 2003 Pal et al., 2009 Tewari-Singh et al., 2009,2010, 2011, 2012, 2013, 2014 Anumolu et al., 2011 Dorandeu et al., 2011 Jain et al., 2011 Vallet et al., 2012). 

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